<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/NCT02208882</url>
  </required_header>
  <id_info>
    <org_study_id>CV004-006</org_study_id>
    <nct_id>NCT02208882</nct_id>
  </id_info>
  <brief_title>Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-986120 in Healthy Subjects and the Effects of Co-Administration of Midazolam and BMS-986120</brief_title>
  <official_title>Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Oral Doses of BMS-986120 in Healthy Subjects and the Effect of BMS-986120 on the Pharmacokinetics of Midazolam in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bristol-Myers Squibb</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the safety, tolerability and effect on Midazolam&#xD;
      pharmacokinetics of multiple oral doses of BMS-986120 in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">February 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability measured by number of subjects experience serious adverse events, deaths, adverse events leading to discontinuation, and potential clinically significant changes in electrocardiogram (ECG) parameters</measure>
    <time_frame>Up to 168 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability measured by percent of subjects experience serious adverse events, deaths, adverse events leading to discontinuation, and potential clinically significant changes in electrocardiogram (ECG) parameters</measure>
    <time_frame>Up to 168 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma concentration (Cmax) of BMS-986120, BMT-141464, Midazolam, and 1'hydroxymidazolam</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum observed plasma concentration (Tmax) of BMS-986120, BMT-141464, Midazolam, and 1'hydroxymidazolam</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve from time zero to 24h [AUC(TAU)] of BMS-986120 and BMT-141464</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration at the end of the dosing Interval (Ctau) of BMS-986120 and BMT-141464</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life (T-HALF) of BMS-986120 and BMT-141464</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent total body clearance (CLT/F) of BMS-986120, Midazolam, and 1'hydroxymidazolam</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC accumulation index (AI_AUC) of BMS-986120 and BMT-141464</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff_AUC) of BMS-986120</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] of BMT-141464</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) of BMT-141464</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of Midazolam and 1'hydroxymidazolam</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of Midazolam and 1'hydroxymidazolam</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight [MR_AUC(INF)] of 1'hydroxymidazolam</measure>
    <time_frame>Part A (Days 1-8), Part B/C (Days 1-19), &amp; Part D (Days 1-22)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in protease-activated receptor-4 - agonist peptide (PAR4-AP) induced platelet aggregation of BMS-986120</measure>
    <time_frame>Part A (Days 1-3) &amp; Part B/C (Days 1-19)</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy Adult Volunteers</condition>
  <arm_group>
    <arm_group_label>Panel 1: BMS-986120 or Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BMS-986120 or Placebo multiple dose by mouth as specified</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel 2: BMS-986120 or Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BMS-986120 or Placebo multiple dose by mouth as specified</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel 3: BMS-986120 or Placebo + Midazolam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BMS-986120 or Placebo (multiple dose) + Midazolam (single dose) by mouth as specified</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel 4: BMS-986120 or Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BMS-986120 or Placebo multiple dose by mouth as specified</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BMS-986120</intervention_name>
    <arm_group_label>Panel 1: BMS-986120 or Placebo</arm_group_label>
    <arm_group_label>Panel 2: BMS-986120 or Placebo</arm_group_label>
    <arm_group_label>Panel 3: BMS-986120 or Placebo + Midazolam</arm_group_label>
    <arm_group_label>Panel 4: BMS-986120 or Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Panel 1: BMS-986120 or Placebo</arm_group_label>
    <arm_group_label>Panel 2: BMS-986120 or Placebo</arm_group_label>
    <arm_group_label>Panel 3: BMS-986120 or Placebo + Midazolam</arm_group_label>
    <arm_group_label>Panel 4: BMS-986120 or Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <arm_group_label>Panel 3: BMS-986120 or Placebo + Midazolam</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        For more information regarding BMS clinical trial participation, please visit&#xD;
        www.BMSStudyConnect.com&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male and female subjects as determined by no clinically significant deviation&#xD;
             from normal in medical history, physical examination, ECGs, and clinical laboratory&#xD;
             determinations&#xD;
&#xD;
          2. Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. BMI=Weight (kg)/[Height(m)]2&#xD;
&#xD;
          3. Women who are not of childbearing potential (i.e., who are postmenopausal or&#xD;
             surgically sterile) and men, ages 18 to 75, inclusive&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concurrent, or use within 2-weeks of study drug administration, of marketed or&#xD;
             investigational, non-steroidal anti-inflammatory compounds (NSAIDS), aspirin or other&#xD;
             antiplatelet agents, oral or parenteral anticoagulants&#xD;
&#xD;
          2. Subjects at screening or prior to first dose with the following abnormal laboratory&#xD;
             values upon repeat testing are excluded:&#xD;
&#xD;
               -  i) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) &gt;upper&#xD;
                  limit of normal (ULN)&#xD;
&#xD;
               -  ii) Total bilirubin &gt;ULN, thyroid-stimulating hormone (TSH) &gt;1.5 x ULN with T4&#xD;
                  within normal limits (Subjects with mild unconjugated hyperbilirubinemia due to&#xD;
                  Gilbert's syndrome are excluded)&#xD;
&#xD;
               -  iii) CK &gt;3 x ULN (unless exercise related and CK-MB within normal limits)&#xD;
&#xD;
               -  iv) Activated partial thromboplastin (aPTT) or Prothrombin Time&#xD;
                  (PT)/International Normalized Ratio (INR) &gt;ULN&#xD;
&#xD;
               -  v) Blood urea nitrogen (BUN) or creatinine (Cr) &gt;ULN&#xD;
&#xD;
          3. Hemoglobin or hematocrit or platelet count &lt;lower limit of normal (LLN)&#xD;
&#xD;
          4. Bleeding time exceeding 8 minutes at pre-dose on Day -1&#xD;
&#xD;
          5. Subjects with micro- or macro-hematuria and/or fecal occult blood detected during&#xD;
             screening, baseline or documented during other recent medical assessment, unless&#xD;
             deemed not clinically significant by the Investigator and Medical Monitor&#xD;
&#xD;
          6. Any significant acute or chronic medical illness&#xD;
&#xD;
          7. Current or recent (within 3 months of study drug administration) gastrointestinal&#xD;
             disease&#xD;
&#xD;
          8. Any major surgery within 12 weeks of study drug administration&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bristol-Myers Squibb</last_name>
    <role>Study Director</role>
    <affiliation>Bristol-Myers Squibb</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ppd Development, Lp</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78744</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.bms.com/studyconnect/Pages/home.aspx</url>
    <description>BMS clinical trial educational resource</description>
  </link>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 5, 2014</study_first_posted>
  <last_update_submitted>July 3, 2015</last_update_submitted>
  <last_update_submitted_qc>July 3, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 7, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>BMS-986120</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02208882
org study id: CV004-006
nct id: NCT02208882
lead sponsor: 
has dmc: No
The purpose of this study is to assess the safety, tolerability and effect on Midazolam
      pharmacokinetics of multiple oral doses of BMS-986120 in healthy subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Safety and tolerability measured by number of subjects experience serious adverse events, deaths, adverse events leading to discontinuation, and potential clinically significant changes in electrocardiogram (ECG) parameters
time frame: Up to 168 days
measure: Safety and tolerability measured by percent of subjects experience serious adverse events, deaths, adverse events leading to discontinuation, and potential clinically significant changes in electrocardiogram (ECG) parameters
time frame: Up to 168 days
measure: Maximum observed plasma concentration (Cmax) of BMS-986120, BMT-141464, Midazolam, and 1'hydroxymidazolam
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: Time of maximum observed plasma concentration (Tmax) of BMS-986120, BMT-141464, Midazolam, and 1'hydroxymidazolam
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: Area under the concentration-time curve from time zero to 24h [AUC(TAU)] of BMS-986120 and BMT-141464
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: Concentration at the end of the dosing Interval (Ctau) of BMS-986120 and BMT-141464
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: Half-life (T-HALF) of BMS-986120 and BMT-141464
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: Apparent total body clearance (CLT/F) of BMS-986120, Midazolam, and 1'hydroxymidazolam
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: AUC accumulation index (AI_AUC) of BMS-986120 and BMT-141464
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff_AUC) of BMS-986120
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] of BMT-141464
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) of BMT-141464
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of Midazolam and 1'hydroxymidazolam
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of Midazolam and 1'hydroxymidazolam
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight [MR_AUC(INF)] of 1'hydroxymidazolam
time frame: Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22)
measure: Change from baseline in protease-activated receptor-4 - agonist peptide (PAR4-AP) induced platelet aggregation of BMS-986120
time frame: Part A (Days 1-3) & Part B/C (Days 1-19)
arm group label: Panel 1: BMS-986120 or Placebo
arm group type: Experimental
description: BMS-986120 or Placebo multiple dose by mouth as specified
arm group label: Panel 2: BMS-986120 or Placebo
arm group type: Experimental
description: BMS-986120 or Placebo multiple dose by mouth as specified
arm group label: Panel 3: BMS-986120 or Placebo + Midazolam
arm group type: Experimental
description: BMS-986120 or Placebo (multiple dose) + Midazolam (single dose) by mouth as specified
arm group label: Panel 4: BMS-986120 or Placebo
arm group type: Experimental
description: BMS-986120 or Placebo multiple dose by mouth as specified
intervention type: Drug
intervention name: BMS-986120
arm group label: Panel 1: BMS-986120 or Placebo
arm group label: Panel 2: BMS-986120 or Placebo
arm group label: Panel 3: BMS-986120 or Placebo + Midazolam
arm group label: Panel 4: BMS-986120 or Placebo
intervention type: Drug
intervention name: Placebo
arm group label: Panel 1: BMS-986120 or Placebo
arm group label: Panel 2: BMS-986120 or Placebo
arm group label: Panel 3: BMS-986120 or Placebo + Midazolam
arm group label: Panel 4: BMS-986120 or Placebo
intervention type: Drug
intervention name: Midazolam
arm group label: Panel 3: BMS-986120 or Placebo + Midazolam
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bristol-Myers Squibb
role: Study Director
affiliation: Bristol-Myers Squibb
facility: 
country: United States
url: http://www.bms.com/studyconnect/Pages/home.aspx
description: BMS clinical trial educational resource
responsible party type: Sponsor
mesh term: Midazolam
mesh term: BMS-986120