<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02236988</url>
  </required_header>
  <id_info>
    <org_study_id>CC-10004-CP-027</org_study_id>
    <nct_id>NCT02236988</nct_id>
  </id_info>
  <brief_title>Study to Evaluate Pharmacokinetics of Prototype Modified-Release Formulations Of Apremilast in Healthy Men</brief_title>
  <official_title>A Phase 1, Open-Label, Single Center Study to Evaluate the Pharmacokinetics of Prototype Modified-Release Formulations Of Apremilast (CC-10004) in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amgen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess up to 12 different oral formulations of apremilast to determine how&#xD;
      much apremilast is absorbed by the body compared to a reference formulation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a single-center, open-label, crossover, single modified-release-dose study in&#xD;
      adult males to evaluate the pharmacokinetics (PK) of prototype modified-release (MR)&#xD;
      formulations compared to the reference immediate-release (IR) apremilast formulation. Within&#xD;
      4 separate groups, participants will be randomly assigned to a treatment sequence. A total of&#xD;
      up to 12 test MR formulations may be evaluated.&#xD;
&#xD;
      Group 1: A 4-sequence, 4-period design to compare three modified-release prototypes with the&#xD;
      reference immediate-release formulation. A total of 16 participants will be enrolled to&#xD;
      obtain at least 12 participants who complete all 4 periods.&#xD;
&#xD;
      Group 2: A 4-sequence, 4-period design to compare three MR prototypes with the reference IR&#xD;
      formulation. Sixteen participants will be enrolled to obtain at least 12 participants who&#xD;
      complete all four periods.&#xD;
&#xD;
      Group 3: A six-sequence, three-period design to compare two MR prototypes with the reference&#xD;
      IR formulation. Eighteen participants will be enrolled to obtain at least 12 participants who&#xD;
      complete all three periods.&#xD;
&#xD;
      Group 4: A 10-sequence, 5-period design to compare four MR prototypes with the reference IR&#xD;
      formulation. Thirty participants will be enrolled to obtain at least 20 participants who&#xD;
      complete all five periods.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 7, 2014</start_date>
  <completion_date type="Actual">September 11, 2014</completion_date>
  <primary_completion_date type="Actual">September 11, 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Group 1: Observed Maximum Plasma Concentration (Cmax) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 1: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 1: Half-life of Apremilast in Terminal Phase (T1/2)</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 1: Apparent Total Plasma Clearance (CL/F) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 1: Apparent Total Volume of Distribution (Vz/F) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 1: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 1: Relative Bioavailability of Apremilast Test Formulations Relative to Reference</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 2: Observed Maximum Plasma Concentration (Cmax) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 2: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 2: Half-life of Apremilast in Terminal Phase (T1/2)</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 2: Apparent Total Plasma Clearance (CL/F) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 2: Apparent Total Volume of Distribution (Vz/F) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 2: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 2: Relative Bioavailability of Apremilast Test Formulations Relative to Reference</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 3: Observed Maximum Plasma Concentration (Cmax) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 3: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 3: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 3: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 3: Half-life of Apremilast in Terminal Phase (T1/2)</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 3: Apparent Total Plasma Clearance (CL/F) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 3: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 3: Relative Bioavailability of Apremilast Test Formulations Relative to Reference</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 4: Observed Maximum Plasma Concentration (Cmax) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 4: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 4: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 4: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 4: Half-life of Apremilast in Terminal Phase (T1/2)</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 4: Apparent Total Plasma Clearance (CL/F) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 4: Apparent Total Volume of Distribution (Vz/F) of Apremilast</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 4: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Group 4: Relative Bioavailability of Apremilast Test Formulations Relative to Reference</measure>
    <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
    <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Group 1: Number of Participants With Treatment-emergent Adverse Events</measure>
    <time_frame>Adverse events were collected for 7 to 10 days after each treatment.</time_frame>
    <description>An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.&#xD;
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.&#xD;
A serious adverse event (SAE) is any AE occurring at any dose that:&#xD;
Resulted in death;&#xD;
Was life-threatening;&#xD;
Required inpatient hospitalization or prolongation of existing hospitalization;&#xD;
Resulted in persistent or significant disability/incapacity;&#xD;
Was a congenital anomaly/birth defect;&#xD;
Constituted an important medical event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Group 2: Number of Participants With Treatment-emergent Adverse Events</measure>
    <time_frame>Adverse events were collected for 7 to 10 days after each treatment.</time_frame>
    <description>An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.&#xD;
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.&#xD;
A serious adverse event (SAE) is any AE occurring at any dose that:&#xD;
Resulted in death;&#xD;
Was life-threatening;&#xD;
Required inpatient hospitalization or prolongation of existing hospitalization;&#xD;
Resulted in persistent or significant disability/incapacity;&#xD;
Was a congenital anomaly/birth defect;&#xD;
Constituted an important medical event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Group 3: Number of Participants With Treatment-emergent Adverse Events</measure>
    <time_frame>Adverse events were collected for 7 to 10 days after each treatment.</time_frame>
    <description>An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.&#xD;
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.&#xD;
A serious adverse event (SAE) is any AE occurring at any dose that:&#xD;
Resulted in death;&#xD;
Was life-threatening;&#xD;
Required inpatient hospitalization or prolongation of existing hospitalization;&#xD;
Resulted in persistent or significant disability/incapacity;&#xD;
Was a congenital anomaly/birth defect;&#xD;
Constituted an important medical event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Group 4: Number of Participants With Treatment-emergent Adverse Events</measure>
    <time_frame>Adverse events were collected for 7 to 10 days after each treatment.</time_frame>
    <description>An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.&#xD;
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.&#xD;
A serious adverse event (SAE) is any AE occurring at any dose that:&#xD;
Resulted in death;&#xD;
Was life-threatening;&#xD;
Required inpatient hospitalization or prolongation of existing hospitalization;&#xD;
Resulted in persistent or significant disability/incapacity;&#xD;
Was a congenital anomaly/birth defect;&#xD;
Constituted an important medical event.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received the following 4 treatments, given in 4 possible sequences (ADBC, BACD, CBDA, and DCAB) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) B) A single oral dose 75 mg apremilast tablet prototype MR 1 C) A single oral dose 75 mg apremilast tablet prototype MR 2 D) A single oral dose 75 mg apremilast capsule prototype MR 3</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received the following 4 treatments, given in 4 possible sequences (AGEF, EAFG, FEGA, and GFAE) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) E) A single oral dose 75 mg apremilast capsule prototype MR 4 F) A single oral dose 75 mg apremilast capsule prototype MR 5 G) A single oral dose 75 mg apremilast capsule prototype MR 6</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received the following 3 treatments, given in 6 possible sequences (AIJ, IJA, JAI, AJI, IAJ, or JIA) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) I) A single oral dose 80 mg apremilast capsule prototype MR 8 J) A single oral dose 80 mg apremilast capsule prototype MR 9</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received the following 5 treatments, given in 10 possible sequences (ALOMN, LMANO, MNLOA, NOMAL, OANLM, NMOLA, ONAML, AOLNM, LAMON, or MLNAO) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) L) A single oral dose 80 mg apremilast capsule prototype MR 11 M) A single oral dose 80 mg apremilast capsule prototype MR 12 N) A single oral dose 80 mg apremilast capsule prototype MR 13 O) A single oral dose 80 mg apremilast capsule prototype MR 14</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Immediate Release</intervention_name>
    <description>30 mg immediate release tablets</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_label>Group 4</arm_group_label>
    <other_name>Otezla</other_name>
    <other_name>CC-10004</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Modified Release 1</intervention_name>
    <description>75 mg oral tablet of prototype modified release (MR) 1</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Modified Release 2</intervention_name>
    <description>75 mg oral tablet of prototype MR 2</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Modified Release 3</intervention_name>
    <description>75 mg oral capsule of prototype MR 3</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Modified Release 4</intervention_name>
    <description>75 mg oral capsule of prototype MR 4</description>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Modified Release 5</intervention_name>
    <description>75 mg oral capsule of prototype MR 5</description>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Modified Release 6</intervention_name>
    <description>75 mg oral capsule of prototype MR 6</description>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Modified Release 8</intervention_name>
    <description>80 mg oral capsule of prototype MR 8</description>
    <arm_group_label>Group 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Modified Release 9</intervention_name>
    <description>80 mg oral capsule of prototype MR 9</description>
    <arm_group_label>Group 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Modified Release 11</intervention_name>
    <description>80 mg oral capsule of prototype MR 11</description>
    <arm_group_label>Group 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Modified Release 12</intervention_name>
    <description>80 mg oral capsule of prototype MR 12</description>
    <arm_group_label>Group 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Modified Release 13</intervention_name>
    <description>80 mg oral capsule of prototype MR 13</description>
    <arm_group_label>Group 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apremilast Modified Release 14</intervention_name>
    <description>80 mg oral capsule of prototype MR 14</description>
    <arm_group_label>Group 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects must satisfy ALL of the following criteria to be eligible for enrollment into the&#xD;
        study:&#xD;
&#xD;
          1. Must understand and voluntarily sign a written informed consent form prior to any&#xD;
             study-related procedures being performed.&#xD;
&#xD;
          2. Must be able to communicate with the investigator, understand and comply with the&#xD;
             requirements of the study, and agree to adhere to restrictions and examination&#xD;
             schedules.&#xD;
&#xD;
          3. Male subjects of any race between 18 to 55 years of age (inclusive), and in good&#xD;
             health as determined by the Investigator.&#xD;
&#xD;
          4. Has a body mass index between 18 and 33 kg/m^2 (inclusive).&#xD;
&#xD;
          5. No clinically significant laboratory tests as determined by the investigator.&#xD;
&#xD;
          6. Must not have a fever, with systolic blood pressure: 90 to 140 mmHg and diastolic&#xD;
             blood pressure: 60 to 90 mmHg, and pulse rate: 40 to 110 bpm (measurements taken while&#xD;
             lying down).&#xD;
&#xD;
          7. Must have a normal or clinically acceptable 12-lead electrocardiogram (ECG).&#xD;
&#xD;
          8. Subjects (including those who have had a vasectomy) who engage in activity in which&#xD;
             conception is possible must use barrier contraception (male latex condom or non-latex&#xD;
             condom not made out of natural [animal] membrane [eg, polyurethane]) while on study&#xD;
             medication, and for 28 days after the last dose of study medication.&#xD;
&#xD;
          9. Must agree to refrain from donating sperm, blood or plasma (other than for this study)&#xD;
             while participating in this study and for at least 28 days after the last dose of&#xD;
             study drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        The presence of ANY of the following will exclude any healthy subject from enrollment into&#xD;
        the study:&#xD;
&#xD;
          1. History of any clinically significant and relevant neurological, gastrointestinal,&#xD;
             renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine,&#xD;
             hematological, allergic disease, drug allergies, or other major disorders.&#xD;
&#xD;
          2. Any condition which places the subject at unacceptable risk if he were to participate&#xD;
             in the study, or confounds the ability to interpret data from the study.&#xD;
&#xD;
          3. Use of any prescribed systemic or topical medication within 30 days of the first dose&#xD;
             administration, unless Sponsor agreement is obtained.&#xD;
&#xD;
          4. Use of any non-prescribed systemic or topical medication (including vitamin/mineral&#xD;
             supplements, and herbal medicines) within 14 days of the first dose administration,&#xD;
             unless Sponsor agreement is obtained.&#xD;
&#xD;
          5. Any surgical or medical condition possibly affecting drug absorption, distribution,&#xD;
             metabolism and excretion, eg, bariatric procedure, colon resection, irritable bowel&#xD;
             syndrome, Crohn's disease, etc. Subjects with cholecytectomy and appendectomy may be&#xD;
             included.&#xD;
&#xD;
          6. Exposure to an investigational drug (new chemical entity) within 30 days prior to the&#xD;
             first dose administration or 5 half-lives of that investigational drug, if known&#xD;
             (whichever is longer).&#xD;
&#xD;
          7. Donated blood or plasma within 8 weeks before the first dose administration to a blood&#xD;
             bank or blood donation center.&#xD;
&#xD;
          8. History of drug abuse (as defined by the current version of the Diagnostic and&#xD;
             Statistical Manual (DSM) within 2 years before dosing, or a positive drug screen&#xD;
             reflecting consumption of illicit drugs.&#xD;
&#xD;
          9. History of alcohol abuse (as defined by the current version of the DSM) within 2 years&#xD;
             before dosing, or a positive alcohol screen.&#xD;
&#xD;
         10. Known to have serum hepatitis, or known to be a carrier of the hepatitis B surface&#xD;
             antigen (HBsAg), or hepatitis C virus (HCV) antibody, or have a positive result to the&#xD;
             test for human immunodeficiency virus (HIV) antibodies at Screening.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MD</last_name>
    <role>Study Director</role>
    <affiliation>Amgen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Covance Clinical Research Unit Inc.</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53704-2526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <results_first_submitted>May 5, 2021</results_first_submitted>
  <results_first_submitted_qc>May 5, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 1, 2021</results_first_posted>
  <last_update_submitted>May 5, 2021</last_update_submitted>
  <last_update_submitted_qc>May 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Apremilast</keyword>
  <keyword>Healthy male subjects</keyword>
  <keyword>Pharmacokinetics</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thalidomide</mesh_term>
    <mesh_term>Apremilast</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.</ipd_time_frame>
    <ipd_access_criteria>Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.</ipd_access_criteria>
    <ipd_url>http://www.amgen.com/datasharing</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted at a single study site in the United States from July 2013 to September 2014.</recruitment_details>
      <pre_assignment_details>This was an open-label crossover study that consisted of 4 groups of participants and tested 12 different modified release (MR) formulations of apremilast versus the reference immediate release (IR) formulation. Within each group participants were randomized to a treatment sequence.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Group 1</title>
          <description>Participants received the following 4 treatments, given in 4 possible sequences (ADBC, BACD, CBDA, and DCAB) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) B) A single oral dose 75 mg apremilast tablet prototype MR 1 C) A single oral dose 75 mg apremilast tablet prototype MR 2 D) A single oral dose 75 mg apremilast capsule prototype MR 3</description>
        </group>
        <group group_id="P2">
          <title>Group 2</title>
          <description>Participants received the following 4 treatments, given in 4 possible sequences (AGEF, EAFG, FEGA, and GFAE) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) E) A single oral dose 75 mg apremilast capsule prototype MR 4 F) A single oral dose 75 mg apremilast capsule prototype MR 5 G) A single oral dose 75 mg apremilast capsule prototype MR 6</description>
        </group>
        <group group_id="P3">
          <title>Group 3</title>
          <description>Participants received the following 3 treatments, given in 6 possible sequences (AIJ, IJA, JAI, AJI, IAJ, or JIA) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) I) A single oral dose 80 mg apremilast capsule prototype MR 8 J) A single oral dose 80 mg apremilast capsule prototype MR 9</description>
        </group>
        <group group_id="P4">
          <title>Group 4</title>
          <description>Participants received the following 5 treatments, given in 10 possible sequences (ALOMN, LMANO, MNLOA, NOMAL, OANLM, NMOLA, ONAML, AOLNM, LAMON, or MLNAO) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) L) A single oral dose 80 mg apremilast capsule prototype MR 11 M) A single oral dose 80 mg apremilast capsule prototype MR 12 N) A single oral dose 80 mg apremilast capsule prototype MR 13 O) A single oral dose 80 mg apremilast capsule prototype MR 14</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="18"/>
                <participants group_id="P4" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="18"/>
                <participants group_id="P4" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Unable to Comply with Study Visits</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Group 1</title>
          <description>Participants received the following 4 treatments, given in 4 possible sequences (ADBC, BACD, CBDA, and DCAB) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) B) A single oral dose 75 mg apremilast tablet prototype MR 1 C) A single oral dose 75 mg apremilast tablet prototype MR 2 D) A single oral dose 75 mg apremilast capsule prototype MR 3</description>
        </group>
        <group group_id="B2">
          <title>Group 2</title>
          <description>Participants received the following 4 treatments, given in 4 possible sequences (AGEF, EAFG, FEGA, and GFAE) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) E) A single oral dose 75 mg apremilast capsule prototype MR 4 F) A single oral dose 75 mg apremilast capsule prototype MR 5 G) A single oral dose 75 mg apremilast capsule prototype MR 6</description>
        </group>
        <group group_id="B3">
          <title>Group 3</title>
          <description>Participants received the following 3 treatments, given in 6 possible sequences (AIJ, IJA, JAI, AJI, IAJ, or JIA) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) I) A single oral dose 80 mg apremilast capsule prototype MR 8 J) A single oral dose 80 mg apremilast capsule prototype MR 9</description>
        </group>
        <group group_id="B4">
          <title>Group 4</title>
          <description>Participants received the following 5 treatments, given in 10 possible sequences (ALOMN, LMANO, MNLOA, NOMAL, OANLM, NMOLA, ONAML, AOLNM, LAMON, or MLNAO) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) L) A single oral dose 80 mg apremilast capsule prototype MR 11 M) A single oral dose 80 mg apremilast capsule prototype MR 12 N) A single oral dose 80 mg apremilast capsule prototype MR 13 O) A single oral dose 80 mg apremilast capsule prototype MR 14</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="18"/>
            <count group_id="B4" value="30"/>
            <count group_id="B5" value="80"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39.1" lower_limit="29" upper_limit="55"/>
                    <measurement group_id="B2" value="34.1" lower_limit="20" upper_limit="50"/>
                    <measurement group_id="B3" value="30.4" lower_limit="21" upper_limit="43"/>
                    <measurement group_id="B4" value="33.3" lower_limit="20" upper_limit="55"/>
                    <measurement group_id="B5" value="34.0" lower_limit="20" upper_limit="55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="30"/>
                    <measurement group_id="B5" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="28"/>
                    <measurement group_id="B5" value="73"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="21"/>
                    <measurement group_id="B5" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.82" lower_limit="22.5" upper_limit="31.6"/>
                    <measurement group_id="B2" value="25.56" lower_limit="21.7" upper_limit="29.1"/>
                    <measurement group_id="B3" value="24.83" lower_limit="20.2" upper_limit="31.2"/>
                    <measurement group_id="B4" value="25.15" lower_limit="20.3" upper_limit="32.4"/>
                    <measurement group_id="B5" value="25.49" lower_limit="20.2" upper_limit="32.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Group 1: Observed Maximum Plasma Concentration (Cmax) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The pharmacokinetic (PK) population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 1: Apremilast Modified Release 1</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 1.</description>
          </group>
          <group group_id="O3">
            <title>Group 1: Apremilast Modified Release 2</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 1: Apremilast Modified Release 3</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 1: Observed Maximum Plasma Concentration (Cmax) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The pharmacokinetic (PK) population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="409.96" spread="34.9"/>
                    <measurement group_id="O2" value="267.85" spread="56.4"/>
                    <measurement group_id="O3" value="329.78" spread="52.2"/>
                    <measurement group_id="O4" value="345.11" spread="41.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an analysis of variance (ANOVA) was performed on the natural log-transformed Cmax value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>65.3</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>55.0</ci_lower_limit>
            <ci_upper_limit>77.6</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 1 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed Cmax value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>80.4</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>67.8</ci_lower_limit>
            <ci_upper_limit>95.5</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 2 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed Cmax value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>84.2</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>70.9</ci_lower_limit>
            <ci_upper_limit>99.9</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 3 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Group 1: Number of Participants With Treatment-emergent Adverse Events</title>
        <description>An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.&#xD;
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.&#xD;
A serious adverse event (SAE) is any AE occurring at any dose that:&#xD;
Resulted in death;&#xD;
Was life-threatening;&#xD;
Required inpatient hospitalization or prolongation of existing hospitalization;&#xD;
Resulted in persistent or significant disability/incapacity;&#xD;
Was a congenital anomaly/birth defect;&#xD;
Constituted an important medical event.</description>
        <time_frame>Adverse events were collected for 7 to 10 days after each treatment.</time_frame>
        <population>Participants who received at least one dose of apremilast.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 1: Apremilast Modified Release 1</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 1.</description>
          </group>
          <group group_id="O3">
            <title>Group 1: Apremilast Modified Release 2</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 1: Apremilast Modified Release 3</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 1: Number of Participants With Treatment-emergent Adverse Events</title>
          <description>An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.&#xD;
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.&#xD;
A serious adverse event (SAE) is any AE occurring at any dose that:&#xD;
Resulted in death;&#xD;
Was life-threatening;&#xD;
Required inpatient hospitalization or prolongation of existing hospitalization;&#xD;
Resulted in persistent or significant disability/incapacity;&#xD;
Was a congenital anomaly/birth defect;&#xD;
Constituted an important medical event.</description>
          <population>Participants who received at least one dose of apremilast.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any treatment-emergent adverse event (TEAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Discontinuations due to adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Deaths</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 1: Apremilast Modified Release 1</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 1.</description>
          </group>
          <group group_id="O3">
            <title>Group 1: Apremilast Modified Release 2</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 1: Apremilast Modified Release 3</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6918.49" spread="47.7"/>
                    <measurement group_id="O2" value="4277.83" spread="88.2"/>
                    <measurement group_id="O3" value="4925.69" spread="67.7"/>
                    <measurement group_id="O4" value="5103.07" spread="54.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-t value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>61.8</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>51.7</ci_lower_limit>
            <ci_upper_limit>73.9</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 1 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-t value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>71.2</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>59.6</ci_lower_limit>
            <ci_upper_limit>85.1</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 2 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-t value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>73.8</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>61.7</ci_lower_limit>
            <ci_upper_limit>88.2</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 3 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 1: Apremilast Modified Release 1</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 1.</description>
          </group>
          <group group_id="O3">
            <title>Group 1: Apremilast Modified Release 2</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 1: Apremilast Modified Release 3</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6955.76" spread="47.9"/>
                    <measurement group_id="O2" value="4330.66" spread="88.2"/>
                    <measurement group_id="O3" value="4961.51" spread="67.8"/>
                    <measurement group_id="O4" value="5147.83" spread="54.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-∞ value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>62.3</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>52.1</ci_lower_limit>
            <ci_upper_limit>74.4</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 1 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-∞ value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>71.3</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>59.7</ci_lower_limit>
            <ci_upper_limit>85.2</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 2 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-∞ value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>74.0</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>62.0</ci_lower_limit>
            <ci_upper_limit>88.4</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 3 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 1: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 1: Apremilast Modified Release 1</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 1.</description>
          </group>
          <group group_id="O3">
            <title>Group 1: Apremilast Modified Release 2</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 1: Apremilast Modified Release 3</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 1: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.00" lower_limit="2.00" upper_limit="5.00"/>
                    <measurement group_id="O2" value="4.00" lower_limit="2.00" upper_limit="8.00"/>
                    <measurement group_id="O3" value="4.00" lower_limit="2.00" upper_limit="8.00"/>
                    <measurement group_id="O4" value="4.00" lower_limit="3.00" upper_limit="14.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0090</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference</param_type>
            <param_value>1.00</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.5</ci_lower_limit>
            <ci_upper_limit>2.00</ci_upper_limit>
            <estimate_desc>Median difference (Apremilast Modified Release 1 - Apremilast Immediate Release) calculated from the Hodges-Lehmann estimate.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0073</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference</param_type>
            <param_value>1.26</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.50</ci_lower_limit>
            <ci_upper_limit>3.00</ci_upper_limit>
            <estimate_desc>Median difference (Apremilast Modified Release 2 - Apremilast Immediate Release) calculated from the Hodges-Lehmann estimate.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference</param_type>
            <param_value>2.00</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.00</ci_lower_limit>
            <ci_upper_limit>3.00</ci_upper_limit>
            <estimate_desc>Median difference (Apremilast Modified Release 3 - Apremilast Immediate Release) calculated from the Hodges-Lehmann estimate</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 1: Half-life of Apremilast in Terminal Phase (T1/2)</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 1: Apremilast Modified Release 1</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 1.</description>
          </group>
          <group group_id="O3">
            <title>Group 1: Apremilast Modified Release 2</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 1: Apremilast Modified Release 3</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 1: Half-life of Apremilast in Terminal Phase (T1/2)</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.12" spread="23.3"/>
                    <measurement group_id="O2" value="7.43" spread="21.7"/>
                    <measurement group_id="O3" value="6.88" spread="22.0"/>
                    <measurement group_id="O4" value="7.29" spread="21.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 1: Apparent Total Plasma Clearance (CL/F) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 1: Apremilast Modified Release 1</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 1.</description>
          </group>
          <group group_id="O3">
            <title>Group 1: Apremilast Modified Release 2</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 1: Apremilast Modified Release 3</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 1: Apparent Total Plasma Clearance (CL/F) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.63" spread="47.9"/>
                    <measurement group_id="O2" value="17.32" spread="88.2"/>
                    <measurement group_id="O3" value="15.12" spread="67.8"/>
                    <measurement group_id="O4" value="14.57" spread="54.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 1: Apparent Total Volume of Distribution (Vz/F) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 1: Apremilast Modified Release 1</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 1.</description>
          </group>
          <group group_id="O3">
            <title>Group 1: Apremilast Modified Release 2</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 2.</description>
          </group>
          <group group_id="O4">
            <title>Group 1: Apremilast Modified Release 3</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 1: Apparent Total Volume of Distribution (Vz/F) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>liters</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.65" spread="32.5"/>
                    <measurement group_id="O2" value="185.65" spread="64.7"/>
                    <measurement group_id="O3" value="149.97" spread="53.5"/>
                    <measurement group_id="O4" value="153.23" spread="34.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 1: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose</title>
        <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Apremilast Modified Release 1</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 1.</description>
          </group>
          <group group_id="O2">
            <title>Group 1: Apremilast Modified Release 2</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 2.</description>
          </group>
          <group group_id="O3">
            <title>Group 1: Apremilast Modified Release 3</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 1: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose</title>
          <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>percent availability</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.85" spread="53.7"/>
                    <measurement group_id="O2" value="45.65" spread="47.0"/>
                    <measurement group_id="O3" value="47.37" spread="22.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 1: Relative Bioavailability of Apremilast Test Formulations Relative to Reference</title>
        <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 1: Apremilast Modified Release 1</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 1.</description>
          </group>
          <group group_id="O2">
            <title>Group 1: Apremilast Modified Release 2</title>
            <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 2.</description>
          </group>
          <group group_id="O3">
            <title>Group 1: Apremilast Modified Release 3</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 3.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 1: Relative Bioavailability of Apremilast Test Formulations Relative to Reference</title>
          <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>percent availability</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.26" spread="53.7"/>
                    <measurement group_id="O2" value="71.33" spread="47.0"/>
                    <measurement group_id="O3" value="74.01" spread="22.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 2: Observed Maximum Plasma Concentration (Cmax) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The pharmacokinetic (PK) population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 2: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Apremilast Modified Release 4</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 4.</description>
          </group>
          <group group_id="O3">
            <title>Group 2: Apremilast Modified Release 5</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 5.</description>
          </group>
          <group group_id="O4">
            <title>Group 2: Apremilast Modified Release 6</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 2: Observed Maximum Plasma Concentration (Cmax) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The pharmacokinetic (PK) population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="405.38" spread="30.2"/>
                    <measurement group_id="O2" value="368.45" spread="37.2"/>
                    <measurement group_id="O3" value="298.96" spread="34.1"/>
                    <measurement group_id="O4" value="325.20" spread="35.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed Cmax value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>90.9</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>81.8</ci_lower_limit>
            <ci_upper_limit>101.1</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 4 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed Cmax value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>73.7</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>66.3</ci_lower_limit>
            <ci_upper_limit>82.0</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 5 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed Cmax value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>80.2</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>72.2</ci_lower_limit>
            <ci_upper_limit>89.2</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 6 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 2: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Apremilast Modified Release 4</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 4.</description>
          </group>
          <group group_id="O3">
            <title>Group 2: Apremilast Modified Release 5</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 5.</description>
          </group>
          <group group_id="O4">
            <title>Group 2: Apremilast Modified Release 6</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6635.78" spread="35.9"/>
                    <measurement group_id="O2" value="5634.92" spread="40.2"/>
                    <measurement group_id="O3" value="4780.60" spread="39.3"/>
                    <measurement group_id="O4" value="5177.46" spread="36.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-t value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>84.9</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>77.5</ci_lower_limit>
            <ci_upper_limit>93.0</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 4 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-t value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>72.0</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>65.8</ci_lower_limit>
            <ci_upper_limit>78.9</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 5 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-t value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>78.0</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>71.2</ci_lower_limit>
            <ci_upper_limit>85.5</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 6 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 2: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Apremilast Modified Release 4</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 4.</description>
          </group>
          <group group_id="O3">
            <title>Group 2: Apremilast Modified Release 5</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 5.</description>
          </group>
          <group group_id="O4">
            <title>Group 2: Apremilast Modified Release 6</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6669.26" spread="36.0"/>
                    <measurement group_id="O2" value="5700.66" spread="40.1"/>
                    <measurement group_id="O3" value="4843.46" spread="38.9"/>
                    <measurement group_id="O4" value="5259.40" spread="35.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-∞ value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>85.5</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>78.1</ci_lower_limit>
            <ci_upper_limit>93.6</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 4 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-∞ value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>72.6</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>66.3</ci_lower_limit>
            <ci_upper_limit>79.5</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 5 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-∞ value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>78.9</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>72.0</ci_lower_limit>
            <ci_upper_limit>86.4</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 6 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 2: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 2: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Apremilast Modified Release 4</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 4.</description>
          </group>
          <group group_id="O3">
            <title>Group 2: Apremilast Modified Release 5</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 5.</description>
          </group>
          <group group_id="O4">
            <title>Group 2: Apremilast Modified Release 6</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 2: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.00" lower_limit="1.00" upper_limit="3.00"/>
                    <measurement group_id="O2" value="4.00" lower_limit="3.00" upper_limit="8.00"/>
                    <measurement group_id="O3" value="3.00" lower_limit="2.00" upper_limit="6.00"/>
                    <measurement group_id="O4" value="4.00" lower_limit="2.00" upper_limit="6.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0002</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference</param_type>
            <param_value>2.00</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.00</ci_lower_limit>
            <ci_upper_limit>3.00</ci_upper_limit>
            <estimate_desc>Median difference (Apremilast Modified Release 4 - Apremilast Immediate Release) calculated from the Hodges-Lehmann estimate.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0049</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference</param_type>
            <param_value>1.02</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.50</ci_lower_limit>
            <ci_upper_limit>2.00</ci_upper_limit>
            <estimate_desc>Median difference (Apremilast Modified Release 5 - Apremilast Immediate Release) calculated from the Hodges-Lehmann estimate.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0010</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference</param_type>
            <param_value>1.50</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.00</ci_lower_limit>
            <ci_upper_limit>2.00</ci_upper_limit>
            <estimate_desc>Median difference (Apremilast Modified Release 6 - Apremilast Immediate Release) calculated from the Hodges-Lehmann estimate</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 2: Half-life of Apremilast in Terminal Phase (T1/2)</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 2: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Apremilast Modified Release 4</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 4.</description>
          </group>
          <group group_id="O3">
            <title>Group 2: Apremilast Modified Release 5</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 5.</description>
          </group>
          <group group_id="O4">
            <title>Group 2: Apremilast Modified Release 6</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 2: Half-life of Apremilast in Terminal Phase (T1/2)</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.16" spread="26.3"/>
                    <measurement group_id="O2" value="8.98" spread="22.9"/>
                    <measurement group_id="O3" value="8.43" spread="28.9"/>
                    <measurement group_id="O4" value="8.75" spread="29.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 2: Apparent Total Plasma Clearance (CL/F) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 2: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Apremilast Modified Release 4</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 4.</description>
          </group>
          <group group_id="O3">
            <title>Group 2: Apremilast Modified Release 5</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 5.</description>
          </group>
          <group group_id="O4">
            <title>Group 2: Apremilast Modified Release 6</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 2: Apparent Total Plasma Clearance (CL/F) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.00" spread="36.0"/>
                    <measurement group_id="O2" value="13.16" spread="40.1"/>
                    <measurement group_id="O3" value="15.48" spread="38.9"/>
                    <measurement group_id="O4" value="14.26" spread="35.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 2: Apparent Total Volume of Distribution (Vz/F) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 2: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Apremilast Modified Release 4</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 4.</description>
          </group>
          <group group_id="O3">
            <title>Group 2: Apremilast Modified Release 5</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 5.</description>
          </group>
          <group group_id="O4">
            <title>Group 2: Apremilast Modified Release 6</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 2: Apparent Total Volume of Distribution (Vz/F) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>liters</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="105.88" spread="35.3"/>
                    <measurement group_id="O2" value="170.51" spread="34.0"/>
                    <measurement group_id="O3" value="188.24" spread="37.5"/>
                    <measurement group_id="O4" value="180.10" spread="48.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 2: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose</title>
        <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 2: Apremilast Modified Release 4</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 4.</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Apremilast Modified Release 5</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 5.</description>
          </group>
          <group group_id="O3">
            <title>Group 2: Apremilast Modified Release 6</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 2: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose</title>
          <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>percent availability</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.71" spread="26.0"/>
                    <measurement group_id="O2" value="46.48" spread="23.5"/>
                    <measurement group_id="O3" value="50.47" spread="13.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 2: Relative Bioavailability of Apremilast Test Formulations Relative to Reference</title>
        <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 2: Apremilast Modified Release 4</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 4.</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Apremilast Modified Release 5</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 5.</description>
          </group>
          <group group_id="O3">
            <title>Group 2: Apremilast Modified Release 6</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 2: Relative Bioavailability of Apremilast Test Formulations Relative to Reference</title>
          <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>percent availability</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.48" spread="26.0"/>
                    <measurement group_id="O2" value="72.62" spread="23.5"/>
                    <measurement group_id="O3" value="78.86" spread="13.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 3: Observed Maximum Plasma Concentration (Cmax) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 3: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 3: Apremilast Modified Release 8</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 8.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Apremilast Modified Release 9</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 3: Observed Maximum Plasma Concentration (Cmax) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="378.59" spread="31.6"/>
                    <measurement group_id="O2" value="344.61" spread="28.7"/>
                    <measurement group_id="O3" value="334.51" spread="33.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed Cmax value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>91.0</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>80.4</ci_lower_limit>
            <ci_upper_limit>103.0</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 8 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed Cmax value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>88.4</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>78.1</ci_lower_limit>
            <ci_upper_limit>100.0</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 9 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 3: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 3: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 3: Apremilast Modified Release 8</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 8.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Apremilast Modified Release 9</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 3: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5493.38" spread="33.7"/>
                    <measurement group_id="O2" value="4427.56" spread="32.7"/>
                    <measurement group_id="O3" value="4310.62" spread="35.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-t value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>80.6</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>73.8</ci_lower_limit>
            <ci_upper_limit>88.0</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 8 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-t value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>78.5</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>71.9</ci_lower_limit>
            <ci_upper_limit>85.7</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 9 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 3: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 3: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 3: Apremilast Modified Release 8</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 8.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Apremilast Modified Release 9</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 3: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5518.28" spread="33.8"/>
                    <measurement group_id="O2" value="4477.63" spread="32.7"/>
                    <measurement group_id="O3" value="4359.49" spread="35.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-∞ value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>81.1</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>74.3</ci_lower_limit>
            <ci_upper_limit>88.6</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 8 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-∞ value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>79.0</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>72.3</ci_lower_limit>
            <ci_upper_limit>86.3</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 9 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 3: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 3: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 3: Apremilast Modified Release 8</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 8.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Apremilast Modified Release 9</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 3: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.00" lower_limit="2.00" upper_limit="5.03"/>
                    <measurement group_id="O2" value="4.00" lower_limit="2.00" upper_limit="6.00"/>
                    <measurement group_id="O3" value="4.00" lower_limit="2.00" upper_limit="6.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0374</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference</param_type>
            <param_value>0.98</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.02</ci_lower_limit>
            <ci_upper_limit>1.50</ci_upper_limit>
            <estimate_desc>Median difference (Apremilast Modified Release 8 - Apremilast Immediate Release) calculated from the Hodges-Lehmann estimate.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.1907</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference</param_type>
            <param_value>0.51</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.00</ci_lower_limit>
            <ci_upper_limit>1.50</ci_upper_limit>
            <estimate_desc>Median difference (Apremilast Modified Release 9 - Apremilast Immediate Release) calculated from the Hodges-Lehmann estimate.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 3: Half-life of Apremilast in Terminal Phase (T1/2)</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 3: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 3: Apremilast Modified Release 8</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 8.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Apremilast Modified Release 9</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 3: Half-life of Apremilast in Terminal Phase (T1/2)</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.45" spread="23.8"/>
                    <measurement group_id="O2" value="6.58" spread="29.2"/>
                    <measurement group_id="O3" value="7.05" spread="27.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 3: Apparent Total Plasma Clearance (CL/F) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 3: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 3: Apremilast Modified Release 8</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 8.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Apremilast Modified Release 9</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 3: Apparent Total Plasma Clearance (CL/F) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.87" spread="33.8"/>
                    <measurement group_id="O2" value="17.87" spread="32.7"/>
                    <measurement group_id="O3" value="18.35" spread="35.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 2: Apparent Total Volume of Distribution (Vz/F) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 3: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 3: Apremilast Modified Release 8</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 8.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Apremilast Modified Release 9</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 2: Apparent Total Volume of Distribution (Vz/F) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>liters</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="101.23" spread="37.2"/>
                    <measurement group_id="O2" value="169.71" spread="34.0"/>
                    <measurement group_id="O3" value="186.69" spread="34.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 3: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose</title>
        <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 3: Apremilast Modified Release 8</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 8.</description>
          </group>
          <group group_id="O2">
            <title>Group 3: Apremilast Modified Release 9</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 3: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose</title>
          <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>percent availability</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.64" spread="21.4"/>
                    <measurement group_id="O2" value="44.44" spread="21.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 3: Relative Bioavailability of Apremilast Test Formulations Relative to Reference</title>
        <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 3: Apremilast Modified Release 8</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 8.</description>
          </group>
          <group group_id="O2">
            <title>Group 3: Apremilast Modified Release 9</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 3: Relative Bioavailability of Apremilast Test Formulations Relative to Reference</title>
          <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>percent availability</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.14" spread="21.4"/>
                    <measurement group_id="O2" value="79.00" spread="21.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 4: Observed Maximum Plasma Concentration (Cmax) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The pharmacokinetic (PK) population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 4: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 4: Apremilast Modified Release 11</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 11.</description>
          </group>
          <group group_id="O3">
            <title>Group 4: Apremilast Modified Release 12</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 12.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Apremilast Modified Release 13</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 13.</description>
          </group>
          <group group_id="O5">
            <title>Group 4: Apremilast Modified Release 14</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 4: Observed Maximum Plasma Concentration (Cmax) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The pharmacokinetic (PK) population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="28"/>
                <count group_id="O5" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="438.90" spread="29.1"/>
                    <measurement group_id="O2" value="480.59" spread="24.9"/>
                    <measurement group_id="O3" value="481.10" spread="29.3"/>
                    <measurement group_id="O4" value="316.43" spread="48.5"/>
                    <measurement group_id="O5" value="450.23" spread="32.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed Cmax value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>109.4</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>98.6</ci_lower_limit>
            <ci_upper_limit>121.3</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 11 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed Cmax value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>107.2</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>96.4</ci_lower_limit>
            <ci_upper_limit>119.2</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 12 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed Cmax value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>72.7</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>65.5</ci_lower_limit>
            <ci_upper_limit>80.8</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 13 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed Cmax value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>103.5</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>93.1</ci_lower_limit>
            <ci_upper_limit>114.9</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 14 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 4: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The pharmacokinetic (PK) population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 4: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 4: Apremilast Modified Release 11</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 11.</description>
          </group>
          <group group_id="O3">
            <title>Group 4: Apremilast Modified Release 12</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 12.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Apremilast Modified Release 13</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 13.</description>
          </group>
          <group group_id="O5">
            <title>Group 4: Apremilast Modified Release 14</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 4: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The pharmacokinetic (PK) population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="28"/>
                <count group_id="O5" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6976.02" spread="32.3"/>
                    <measurement group_id="O2" value="5701.21" spread="34.1"/>
                    <measurement group_id="O3" value="5811.24" spread="29.0"/>
                    <measurement group_id="O4" value="4700.70" spread="40.2"/>
                    <measurement group_id="O5" value="5324.80" spread="36.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-t value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>81.5</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>75.2</ci_lower_limit>
            <ci_upper_limit>88.3</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 11 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-t value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>82.4</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>75.9</ci_lower_limit>
            <ci_upper_limit>89.5</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 12 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-t value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>68.2</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>62.9</ci_lower_limit>
            <ci_upper_limit>74.0</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 13 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-t value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>77.4</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>71.3</ci_lower_limit>
            <ci_upper_limit>84.0</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 14 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 4: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 4: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 4: Apremilast Modified Release 11</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 11.</description>
          </group>
          <group group_id="O3">
            <title>Group 4: Apremilast Modified Release 12</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 12.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Apremilast Modified Release 13</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 13.</description>
          </group>
          <group group_id="O5">
            <title>Group 4: Apremilast Modified Release 14</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 4: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="28"/>
                <count group_id="O5" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7000.35" spread="32.2"/>
                    <measurement group_id="O2" value="5747.12" spread="34.0"/>
                    <measurement group_id="O3" value="5875.19" spread="28.6"/>
                    <measurement group_id="O4" value="4753.79" spread="40.1"/>
                    <measurement group_id="O5" value="5374.83" spread="36.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-∞ value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>81.9</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>75.6</ci_lower_limit>
            <ci_upper_limit>88.6</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 11 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-∞ value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>83.0</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>76.5</ci_lower_limit>
            <ci_upper_limit>90.1</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 12 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-∞ value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>68.8</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>63.4</ci_lower_limit>
            <ci_upper_limit>74.5</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 13 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>To compare each test formulation with the reference formulation in each group, an ANOVA was performed on the natural log-transformed AUC0-∞ value. The ANOVA model included treatment, sequence, and period as fixed effects and subject nested within sequence as a random effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Adjusted Geometric Means</param_type>
            <param_value>77.8</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>71.8</ci_lower_limit>
            <ci_upper_limit>84.4</ci_upper_limit>
            <estimate_desc>Ratio of adjusted geometric means (Apremilast Modified Release 14 / Apremilast Immediate Release) expressed as a percentage.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 4: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 4: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 4: Apremilast Modified Release 11</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 11.</description>
          </group>
          <group group_id="O3">
            <title>Group 4: Apremilast Modified Release 12</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 12.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Apremilast Modified Release 13</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 13.</description>
          </group>
          <group group_id="O5">
            <title>Group 4: Apremilast Modified Release 14</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 4: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="28"/>
                <count group_id="O5" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.00" lower_limit="1.00" upper_limit="5.08"/>
                    <measurement group_id="O2" value="4.00" lower_limit="2.00" upper_limit="6.00"/>
                    <measurement group_id="O3" value="4.00" lower_limit="2.00" upper_limit="6.00"/>
                    <measurement group_id="O4" value="4.01" lower_limit="2.00" upper_limit="14.00"/>
                    <measurement group_id="O5" value="3.52" lower_limit="2.00" upper_limit="6.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0523</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference</param_type>
            <param_value>0.98</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.03</ci_lower_limit>
            <ci_upper_limit>1.50</ci_upper_limit>
            <estimate_desc>Median difference (Apremilast Modified Release 11 - Apremilast Immediate Release) calculated from the Hodges-Lehmann estimate.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.2598</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference</param_type>
            <param_value>0.50</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.00</ci_lower_limit>
            <ci_upper_limit>1.00</ci_upper_limit>
            <estimate_desc>Median difference (Apremilast Modified Release 12 - Apremilast Immediate Release) calculated from the Hodges-Lehmann estimate.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0053</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference</param_type>
            <param_value>1.50</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.00</ci_lower_limit>
            <ci_upper_limit>3.00</ci_upper_limit>
            <estimate_desc>Median difference (Apremilast Modified Release 13 - Apremilast Immediate Release) calculated from the Hodges-Lehmann estimate.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>Tmax was analyzed by nonparametric methods. The median difference and 90% CI of the median difference were calculated from the Hodges-Lehrmann estimate.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.1093</p_value>
            <method>Wilcoxon signed-rank test</method>
            <param_type>Median Difference</param_type>
            <param_value>0.50</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.00</ci_lower_limit>
            <ci_upper_limit>1.00</ci_upper_limit>
            <estimate_desc>Median difference (Apremilast Modified Release 14 - Apremilast Immediate Release) calculated from the Hodges-Lehmann estimate.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 4: Half-life of Apremilast in Terminal Phase (T1/2)</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 4: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 4: Apremilast Modified Release 11</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 11.</description>
          </group>
          <group group_id="O3">
            <title>Group 4: Apremilast Modified Release 12</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 12.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Apremilast Modified Release 13</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 13.</description>
          </group>
          <group group_id="O5">
            <title>Group 4: Apremilast Modified Release 14</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 4: Half-life of Apremilast in Terminal Phase (T1/2)</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="28"/>
                <count group_id="O5" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.25" spread="24.8"/>
                    <measurement group_id="O2" value="7.40" spread="25.2"/>
                    <measurement group_id="O3" value="7.51" spread="34.9"/>
                    <measurement group_id="O4" value="7.09" spread="31.0"/>
                    <measurement group_id="O5" value="7.13" spread="32.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 4: Apparent Total Plasma Clearance (CL/F) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 4: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 4: Apremilast Modified Release 11</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 11.</description>
          </group>
          <group group_id="O3">
            <title>Group 4: Apremilast Modified Release 12</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 12.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Apremilast Modified Release 13</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 13.</description>
          </group>
          <group group_id="O5">
            <title>Group 4: Apremilast Modified Release 14</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 4: Apparent Total Plasma Clearance (CL/F) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="28"/>
                <count group_id="O5" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.57" spread="32.2"/>
                    <measurement group_id="O2" value="13.92" spread="34.0"/>
                    <measurement group_id="O3" value="13.62" spread="28.6"/>
                    <measurement group_id="O4" value="16.83" spread="40.1"/>
                    <measurement group_id="O5" value="14.88" spread="36.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 4: Apparent Total Volume of Distribution (Vz/F) of Apremilast</title>
        <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 4: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 4: Apremilast Modified Release 11</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 11.</description>
          </group>
          <group group_id="O3">
            <title>Group 4: Apremilast Modified Release 12</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 12.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Apremilast Modified Release 13</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 13.</description>
          </group>
          <group group_id="O5">
            <title>Group 4: Apremilast Modified Release 14</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 4: Apparent Total Volume of Distribution (Vz/F) of Apremilast</title>
          <description>Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>liters</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="28"/>
                <count group_id="O5" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.30" spread="36.0"/>
                    <measurement group_id="O2" value="148.66" spread="32.5"/>
                    <measurement group_id="O3" value="147.59" spread="41.5"/>
                    <measurement group_id="O4" value="172.16" spread="44.6"/>
                    <measurement group_id="O5" value="153.18" spread="36.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 4: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose</title>
        <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 4: Apremilast Modified Release 11</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 11.</description>
          </group>
          <group group_id="O2">
            <title>Group 4: Apremilast Modified Release 12</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 12.</description>
          </group>
          <group group_id="O3">
            <title>Group 4: Apremilast Modified Release 13</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 13.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Apremilast Modified Release 14</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 4: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose</title>
          <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>percent availability</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="27"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.18" spread="22.3"/>
                    <measurement group_id="O2" value="46.86" spread="27.7"/>
                    <measurement group_id="O3" value="38.65" spread="34.0"/>
                    <measurement group_id="O4" value="43.70" spread="26.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Group 4: Relative Bioavailability of Apremilast Test Formulations Relative to Reference</title>
        <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.</description>
        <time_frame>IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.</time_frame>
        <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 4: Apremilast Modified Release 11</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 11.</description>
          </group>
          <group group_id="O2">
            <title>Group 4: Apremilast Modified Release 12</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 12.</description>
          </group>
          <group group_id="O3">
            <title>Group 4: Apremilast Modified Release 13</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 13.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Apremilast Modified Release 14</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 4: Relative Bioavailability of Apremilast Test Formulations Relative to Reference</title>
          <description>Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:&#xD;
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.</description>
          <population>The PK population included all participants who received at least one dose of apremilast and had evaluable PK profiles.</population>
          <units>percent availability</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="27"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.10" spread="22.3"/>
                    <measurement group_id="O2" value="83.31" spread="27.7"/>
                    <measurement group_id="O3" value="68.71" spread="34.0"/>
                    <measurement group_id="O4" value="77.68" spread="26.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Group 2: Number of Participants With Treatment-emergent Adverse Events</title>
        <description>An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.&#xD;
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.&#xD;
A serious adverse event (SAE) is any AE occurring at any dose that:&#xD;
Resulted in death;&#xD;
Was life-threatening;&#xD;
Required inpatient hospitalization or prolongation of existing hospitalization;&#xD;
Resulted in persistent or significant disability/incapacity;&#xD;
Was a congenital anomaly/birth defect;&#xD;
Constituted an important medical event.</description>
        <time_frame>Adverse events were collected for 7 to 10 days after each treatment.</time_frame>
        <population>Participants who received at least one dose of apremilast.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 2: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 2: Apremilast Modified Release 4</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 4.</description>
          </group>
          <group group_id="O3">
            <title>Group 2: Apremilast Modified Release 5</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 5.</description>
          </group>
          <group group_id="O4">
            <title>Group 2: Apremilast Modified Release 6</title>
            <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 6.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 2: Number of Participants With Treatment-emergent Adverse Events</title>
          <description>An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.&#xD;
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.&#xD;
A serious adverse event (SAE) is any AE occurring at any dose that:&#xD;
Resulted in death;&#xD;
Was life-threatening;&#xD;
Required inpatient hospitalization or prolongation of existing hospitalization;&#xD;
Resulted in persistent or significant disability/incapacity;&#xD;
Was a congenital anomaly/birth defect;&#xD;
Constituted an important medical event.</description>
          <population>Participants who received at least one dose of apremilast.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any treatment-emergent adverse event (TEAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Discontinuations due to adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Deaths</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Group 3: Number of Participants With Treatment-emergent Adverse Events</title>
        <description>An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.&#xD;
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.&#xD;
A serious adverse event (SAE) is any AE occurring at any dose that:&#xD;
Resulted in death;&#xD;
Was life-threatening;&#xD;
Required inpatient hospitalization or prolongation of existing hospitalization;&#xD;
Resulted in persistent or significant disability/incapacity;&#xD;
Was a congenital anomaly/birth defect;&#xD;
Constituted an important medical event.</description>
        <time_frame>Adverse events were collected for 7 to 10 days after each treatment.</time_frame>
        <population>Participants who received at least one dose of apremilast.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 3: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 3: Apremilast Modified Release 8</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 8.</description>
          </group>
          <group group_id="O3">
            <title>Group 3: Apremilast Modified Release 9</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 9.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 3: Number of Participants With Treatment-emergent Adverse Events</title>
          <description>An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.&#xD;
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.&#xD;
A serious adverse event (SAE) is any AE occurring at any dose that:&#xD;
Resulted in death;&#xD;
Was life-threatening;&#xD;
Required inpatient hospitalization or prolongation of existing hospitalization;&#xD;
Resulted in persistent or significant disability/incapacity;&#xD;
Was a congenital anomaly/birth defect;&#xD;
Constituted an important medical event.</description>
          <population>Participants who received at least one dose of apremilast.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any treatment-emergent adverse event (TEAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Discontinuations due to adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Deaths</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Group 4: Number of Participants With Treatment-emergent Adverse Events</title>
        <description>An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.&#xD;
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.&#xD;
A serious adverse event (SAE) is any AE occurring at any dose that:&#xD;
Resulted in death;&#xD;
Was life-threatening;&#xD;
Required inpatient hospitalization or prolongation of existing hospitalization;&#xD;
Resulted in persistent or significant disability/incapacity;&#xD;
Was a congenital anomaly/birth defect;&#xD;
Constituted an important medical event.</description>
        <time_frame>Adverse events were collected for 7 to 10 days after each treatment.</time_frame>
        <population>Participants who received at least one dose of apremilast.</population>
        <group_list>
          <group group_id="O1">
            <title>Group 4: Apremilast Immediate Release</title>
            <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
          </group>
          <group group_id="O2">
            <title>Group 4: Apremilast Modified Release 11</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 11.</description>
          </group>
          <group group_id="O3">
            <title>Group 4: Apremilast Modified Release 12</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 12.</description>
          </group>
          <group group_id="O4">
            <title>Group 4: Apremilast Modified Release 13</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 13.</description>
          </group>
          <group group_id="O5">
            <title>Group 4: Apremilast Modified Release 14</title>
            <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 14.</description>
          </group>
        </group_list>
        <measure>
          <title>Group 4: Number of Participants With Treatment-emergent Adverse Events</title>
          <description>An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.&#xD;
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.&#xD;
A serious adverse event (SAE) is any AE occurring at any dose that:&#xD;
Resulted in death;&#xD;
Was life-threatening;&#xD;
Required inpatient hospitalization or prolongation of existing hospitalization;&#xD;
Resulted in persistent or significant disability/incapacity;&#xD;
Was a congenital anomaly/birth defect;&#xD;
Constituted an important medical event.</description>
          <population>Participants who received at least one dose of apremilast.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="28"/>
                <count group_id="O5" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any treatment-emergent adverse event (TEAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="7"/>
                    <measurement group_id="O4" value="7"/>
                    <measurement group_id="O5" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="6"/>
                    <measurement group_id="O5" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events related to study drug</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Discontinuation due to adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Deaths</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected for 7 to 10 days after each treatment.</time_frame>
      <desc>Adverse events are reported for all participants who received at least one dose of apremilast.</desc>
      <group_list>
        <group group_id="E1">
          <title>Group 1: Apremilast Immediate Release</title>
          <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
        </group>
        <group group_id="E2">
          <title>Group 1: Apremilast Modified Release 1</title>
          <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 1.</description>
        </group>
        <group group_id="E3">
          <title>Group 1: Apremilast Modified Release 2</title>
          <description>Participants received a single oral dose 75 mg apremilast tablet prototype MR 2.</description>
        </group>
        <group group_id="E4">
          <title>Group 1: Apremilast Modified Release 3</title>
          <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 3.</description>
        </group>
        <group group_id="E5">
          <title>Group 1 Total</title>
          <description>Participants received the following 4 treatments, given in 4 possible sequences (ADBC, BACD, CBDA, and DCAB) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) B) A single oral dose 75 mg apremilast tablet prototype MR 1 C) A single oral dose 75 mg apremilast tablet prototype MR 2 D) A single oral dose 75 mg apremilast capsule prototype MR 3.</description>
        </group>
        <group group_id="E6">
          <title>Group 2: Apremilast Immediate Release</title>
          <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
        </group>
        <group group_id="E7">
          <title>Group 2: Apremilast Modified Release 4</title>
          <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 4.</description>
        </group>
        <group group_id="E8">
          <title>Group 2: Apremilast Modified Release 5</title>
          <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 5.</description>
        </group>
        <group group_id="E9">
          <title>Group 2: Apremilast Modified Release 6</title>
          <description>Participants received a single oral dose 75 mg apremilast capsule prototype MR 6.</description>
        </group>
        <group group_id="E10">
          <title>Group 2 Total</title>
          <description>Participants received the following 4 treatments, given in 4 possible sequences (AGEF, EAFG, FEGA, and GFAE) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) E) A single oral dose 75 mg apremilast capsule prototype MR 4 F) A single oral dose 75 mg apremilast capsule prototype MR 5 G) A single oral dose 75 mg apremilast capsule prototype MR 6</description>
        </group>
        <group group_id="E11">
          <title>Group 3: Apremilast Immediate Release</title>
          <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
        </group>
        <group group_id="E12">
          <title>Group 3: Apremilast Modified Release 8</title>
          <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 8.</description>
        </group>
        <group group_id="E13">
          <title>Group 3: Apremilast Modified Release 9</title>
          <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 9.</description>
        </group>
        <group group_id="E14">
          <title>Group 3 Total</title>
          <description>Participants received the following 3 treatments, given in 6 possible sequences (AIJ, IJA, JAI, AJI, IAJ, or JIA) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) I) A single oral dose 80 mg apremilast capsule prototype MR 8 J) A single oral dose 80 mg apremilast capsule prototype MR 9</description>
        </group>
        <group group_id="E15">
          <title>Group 4: Apremilast Immediate Release</title>
          <description>Participants received two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation).</description>
        </group>
        <group group_id="E16">
          <title>Group 4: Apremilast Modified Release 11</title>
          <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 11.</description>
        </group>
        <group group_id="E17">
          <title>Group 4: Apremilast Modified Release 12</title>
          <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 12.</description>
        </group>
        <group group_id="E18">
          <title>Group 4: Apremilast Modified Release 13</title>
          <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 13.</description>
        </group>
        <group group_id="E19">
          <title>Group 4: Apremilast Modified Release 14</title>
          <description>Participants received a single oral dose 80 mg apremilast capsule prototype MR 14.</description>
        </group>
        <group group_id="E20">
          <title>Group 4 Total</title>
          <description>Participants received the following 5 treatments, given in 10 possible sequences (ALOMN, LMANO, MNLOA, NOMAL, OANLM, NMOLA, ONAML, AOLNM, LAMON, or MLNAO) with 7 to 10 days between each treatment:&#xD;
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) L) A single oral dose 80 mg apremilast capsule prototype MR 11 M) A single oral dose 80 mg apremilast capsule prototype MR 12 N) A single oral dose 80 mg apremilast capsule prototype MR 13 O) A single oral dose 80 mg apremilast capsule prototype MR 14</description>
        </group>
        <group group_id="E21">
          <title>Overall Total</title>
          <description>All participants who received any dose of apremilast during the study.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 16.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="6" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="8" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="7" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="12" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="7" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="5" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="7" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="17" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="40" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>CONJUNCTIVAL HYPERAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>VISION BLURRED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL DISCOMFORT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="7" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>ABDOMINAL PAIN UPPER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="2" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>CHANGE OF BOWEL HABIT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="6" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>DRY MOUTH</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>HAEMORRHOIDS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="11" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>FOLLICULITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>GASTROENTERITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="3" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>VIRAL UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="3" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>ARTHROPOD STING</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>LACERATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="3" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>PROCEDURAL COMPLICATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="2" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>PROCEDURAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="3" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>PROCEDURAL SITE REACTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="5" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>PAIN IN EXTREMITY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="2" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="6" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>DYSGEUSIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="8" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="13" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="22" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>PRESYNCOPE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="3" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>SYNCOPE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>DRY THROAT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>OROPHARYNGEAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>RHINORRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ERYTHEMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E8" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E9" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E10" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E11" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E12" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E13" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E14" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E15" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E16" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E17" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E18" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E19" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E20" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E21" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Amgen Inc.</organization>
      <phone>866-572-6436</phone>
      <email>medinfo@amgen.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02236988
org study id: CC-10004-CP-027
nct id: NCT02236988
lead sponsor: 
has dmc: No
This study will assess up to 12 different oral formulations of apremilast to determine how
      much apremilast is absorbed by the body compared to a reference formulation.
This will be a single-center, open-label, crossover, single modified-release-dose study in
      adult males to evaluate the pharmacokinetics (PK) of prototype modified-release (MR)
      formulations compared to the reference immediate-release (IR) apremilast formulation. Within
      4 separate groups, participants will be randomly assigned to a treatment sequence. A total of
      up to 12 test MR formulations may be evaluated.

      Group 1: A 4-sequence, 4-period design to compare three modified-release prototypes with the
      reference immediate-release formulation. A total of 16 participants will be enrolled to
      obtain at least 12 participants who complete all 4 periods.

      Group 2: A 4-sequence, 4-period design to compare three MR prototypes with the reference IR
      formulation. Sixteen participants will be enrolled to obtain at least 12 participants who
      complete all four periods.

      Group 3: A six-sequence, three-period design to compare two MR prototypes with the reference
      IR formulation. Eighteen participants will be enrolled to obtain at least 12 participants who
      complete all three periods.

      Group 4: A 10-sequence, 5-period design to compare four MR prototypes with the reference IR
      formulation. Thirty participants will be enrolled to obtain at least 20 participants who
      complete all five periods.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Group 1: Observed Maximum Plasma Concentration (Cmax) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 1: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 1: Half-life of Apremilast in Terminal Phase (T1/2)
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 1: Apparent Total Plasma Clearance (CL/F) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 1: Apparent Total Volume of Distribution (Vz/F) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 1: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.
measure: Group 1: Relative Bioavailability of Apremilast Test Formulations Relative to Reference
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.
measure: Group 2: Observed Maximum Plasma Concentration (Cmax) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 2: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 2: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 2: Half-life of Apremilast in Terminal Phase (T1/2)
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 2: Apparent Total Plasma Clearance (CL/F) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 2: Apparent Total Volume of Distribution (Vz/F) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 2: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.
measure: Group 2: Relative Bioavailability of Apremilast Test Formulations Relative to Reference
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.
measure: Group 3: Observed Maximum Plasma Concentration (Cmax) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 3: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 3: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 3: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 3: Half-life of Apremilast in Terminal Phase (T1/2)
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 3: Apparent Total Plasma Clearance (CL/F) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 3: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.
measure: Group 3: Relative Bioavailability of Apremilast Test Formulations Relative to Reference
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.
measure: Group 4: Observed Maximum Plasma Concentration (Cmax) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 4: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-t) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 4: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 4: Time to Observed Maximum Plasma Concentration (Tmax) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 4: Half-life of Apremilast in Terminal Phase (T1/2)
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 4: Apparent Total Plasma Clearance (CL/F) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 4: Apparent Total Volume of Distribution (Vz/F) of Apremilast
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay.
measure: Group 4: Relative Bioavailability of Apremilast Test Formulations Relative to Reference Corrected by Dose
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:
(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%.
measure: Group 4: Relative Bioavailability of Apremilast Test Formulations Relative to Reference
time frame: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
description: Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:
(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%.
measure: Group 1: Number of Participants With Treatment-emergent Adverse Events
time frame: Adverse events were collected for 7 to 10 days after each treatment.
description: An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.
A serious adverse event (SAE) is any AE occurring at any dose that:
Resulted in death;
Was life-threatening;
Required inpatient hospitalization or prolongation of existing hospitalization;
Resulted in persistent or significant disability/incapacity;
Was a congenital anomaly/birth defect;
Constituted an important medical event.
measure: Group 2: Number of Participants With Treatment-emergent Adverse Events
time frame: Adverse events were collected for 7 to 10 days after each treatment.
description: An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.
A serious adverse event (SAE) is any AE occurring at any dose that:
Resulted in death;
Was life-threatening;
Required inpatient hospitalization or prolongation of existing hospitalization;
Resulted in persistent or significant disability/incapacity;
Was a congenital anomaly/birth defect;
Constituted an important medical event.
measure: Group 3: Number of Participants With Treatment-emergent Adverse Events
time frame: Adverse events were collected for 7 to 10 days after each treatment.
description: An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.
A serious adverse event (SAE) is any AE occurring at any dose that:
Resulted in death;
Was life-threatening;
Required inpatient hospitalization or prolongation of existing hospitalization;
Resulted in persistent or significant disability/incapacity;
Was a congenital anomaly/birth defect;
Constituted an important medical event.
measure: Group 4: Number of Participants With Treatment-emergent Adverse Events
time frame: Adverse events were collected for 7 to 10 days after each treatment.
description: An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.
A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.
A serious adverse event (SAE) is any AE occurring at any dose that:
Resulted in death;
Was life-threatening;
Required inpatient hospitalization or prolongation of existing hospitalization;
Resulted in persistent or significant disability/incapacity;
Was a congenital anomaly/birth defect;
Constituted an important medical event.
arm group label: Group 1
arm group type: Experimental
description: Participants received the following 4 treatments, given in 4 possible sequences (ADBC, BACD, CBDA, and DCAB) with 7 to 10 days between each treatment:
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) B) A single oral dose 75 mg apremilast tablet prototype MR 1 C) A single oral dose 75 mg apremilast tablet prototype MR 2 D) A single oral dose 75 mg apremilast capsule prototype MR 3
arm group label: Group 2
arm group type: Experimental
description: Participants received the following 4 treatments, given in 4 possible sequences (AGEF, EAFG, FEGA, and GFAE) with 7 to 10 days between each treatment:
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) E) A single oral dose 75 mg apremilast capsule prototype MR 4 F) A single oral dose 75 mg apremilast capsule prototype MR 5 G) A single oral dose 75 mg apremilast capsule prototype MR 6
arm group label: Group 3
arm group type: Experimental
description: Participants received the following 3 treatments, given in 6 possible sequences (AIJ, IJA, JAI, AJI, IAJ, or JIA) with 7 to 10 days between each treatment:
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) I) A single oral dose 80 mg apremilast capsule prototype MR 8 J) A single oral dose 80 mg apremilast capsule prototype MR 9
arm group label: Group 4
arm group type: Experimental
description: Participants received the following 5 treatments, given in 10 possible sequences (ALOMN, LMANO, MNLOA, NOMAL, OANLM, NMOLA, ONAML, AOLNM, LAMON, or MLNAO) with 7 to 10 days between each treatment:
A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) L) A single oral dose 80 mg apremilast capsule prototype MR 11 M) A single oral dose 80 mg apremilast capsule prototype MR 12 N) A single oral dose 80 mg apremilast capsule prototype MR 13 O) A single oral dose 80 mg apremilast capsule prototype MR 14
intervention type: Drug
intervention name: Apremilast Immediate Release
description: 30 mg immediate release tablets
arm group label: Group 1
arm group label: Group 2
arm group label: Group 3
arm group label: Group 4
other name: Otezla
other name: CC-10004
intervention type: Drug
intervention name: Apremilast Modified Release 1
description: 75 mg oral tablet of prototype modified release (MR) 1
arm group label: Group 1
intervention type: Drug
intervention name: Apremilast Modified Release 2
description: 75 mg oral tablet of prototype MR 2
arm group label: Group 1
intervention type: Drug
intervention name: Apremilast Modified Release 3
description: 75 mg oral capsule of prototype MR 3
arm group label: Group 1
intervention type: Drug
intervention name: Apremilast Modified Release 4
description: 75 mg oral capsule of prototype MR 4
arm group label: Group 2
intervention type: Drug
intervention name: Apremilast Modified Release 5
description: 75 mg oral capsule of prototype MR 5
arm group label: Group 2
intervention type: Drug
intervention name: Apremilast Modified Release 6
description: 75 mg oral capsule of prototype MR 6
arm group label: Group 2
intervention type: Drug
intervention name: Apremilast Modified Release 8
description: 80 mg oral capsule of prototype MR 8
arm group label: Group 3
intervention type: Drug
intervention name: Apremilast Modified Release 9
description: 80 mg oral capsule of prototype MR 9
arm group label: Group 3
intervention type: Drug
intervention name: Apremilast Modified Release 11
description: 80 mg oral capsule of prototype MR 11
arm group label: Group 4
intervention type: Drug
intervention name: Apremilast Modified Release 12
description: 80 mg oral capsule of prototype MR 12
arm group label: Group 4
intervention type: Drug
intervention name: Apremilast Modified Release 13
description: 80 mg oral capsule of prototype MR 13
arm group label: Group 4
intervention type: Drug
intervention name: Apremilast Modified Release 14
description: 80 mg oral capsule of prototype MR 14
arm group label: Group 4
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: MD
role: Study Director
affiliation: Amgen
facility: 
country: United States
responsible party type: Sponsor
mesh term: Thalidomide
mesh term: Apremilast
sharing ipd: Yes
ipd description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
ipd access criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
ipd url: http://www.amgen.com/datasharing
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 