<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/NCT03297983</url>
  </required_header>
  <id_info>
    <org_study_id>MS200662-0017</org_study_id>
    <secondary_id>2017-001674-41</secondary_id>
    <nct_id>NCT03297983</nct_id>
  </id_info>
  <brief_title>M7583 Relative Bioavailability of Tablet Compared to Powder-in-capsule</brief_title>
  <official_title>Phase I, Open-label, Randomized, Two Part, Three-Period, Two-Sequence, Cross-over Study to Investigate the Relative Bioavailability of a Tablet Formulation Compared to Powder-in-Capsule of M7583 Including a Food Effect Evaluation for the Tablet in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck KGaA, Darmstadt, Germany</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck KGaA, Darmstadt, Germany</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase I study consisting of 2 parts: Part 1 aims to investigate the relative&#xD;
      bioavailability of tablet formulation (test treatment) and Powder in capsule (PiC)&#xD;
      formulation (reference treatment) of M7583 under fasted conditions. The aim of Part 2 is to&#xD;
      determine and compare the single dose Pharmacokinetic (PK) profile of M7583 tablet under&#xD;
      fasted and fed conditions to assess the food effect.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 9, 2017</start_date>
  <completion_date type="Actual">December 6, 2017</completion_date>
  <primary_completion_date type="Actual">December 6, 2017</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>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concnetration (AUC0-t) of M7583</measure>
    <time_frame>pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of M7583</measure>
    <time_frame>pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Drug Concentration (Cmax) of M7583</measure>
    <time_frame>pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs</measure>
    <time_frame>Up to Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Subjects With TEAEs by Severity According to Qualitative Toxicity Scale Selected From National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE) version 4.03</measure>
    <time_frame>Up to Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects with Clinically Significant Change From Baseline in Laboratory Tests, Vital Sign and 12-lead Electrocardiogram (ECG) Findings</measure>
    <time_frame>Up to Week 6</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach the Maximum Plasma Concentration (tmax) of M7583</measure>
    <time_frame>pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Rate Constant (λz) of M7583</measure>
    <time_frame>pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Half-life (t1/2) of M7583</measure>
    <time_frame>pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Body Clearance of Drug From Plasma Following Oral Administration (CL/f) of M7583</measure>
    <time_frame>pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution (Vz/f) of M7583</measure>
    <time_frame>pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the M7583 Plasma Concentration-time Curve From Time Zero to 24 hours After Dosing (AUC0-24h)</measure>
    <time_frame>pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of AUC0-∞ Obtained by Extrapolation (%AUCextra) of M7583</measure>
    <time_frame>pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative Bioavailability of M7583 Tablet versus M7583 PIC (Frel,T/P)</measure>
    <time_frame>pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative Bioavailability of M7583 Tablet Administered 30 Minutes After a Standard Breakfast Versus Tablet Administered After an Overnight Fast (Frel,Fed/Fasted)</measure>
    <time_frame>pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>First M7583 Tablet:Fasted, Then PiC:Fasted, Then Tablet:Fed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>First M7583 PiC:Fasted, Then Tablet:Fasted, Then Tablet:Fed</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>M7583</intervention_name>
    <description>Subject will receive either M7583 PiC or M7583 tablet formulation orally under fasted conditions in part 1 followed by M7583 tablet formulation under fed condition in part 2 of the study.</description>
    <arm_group_label>First M7583 PiC:Fasted, Then Tablet:Fasted, Then Tablet:Fed</arm_group_label>
    <arm_group_label>First M7583 Tablet:Fasted, Then PiC:Fasted, Then Tablet:Fed</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult males and females between 18 and 55 years of age (inclusive) with total body&#xD;
             weight between 50.0 and 100.0 kilogram (kg) (inclusive) and body mass index (BMI)&#xD;
             between 19.0 and 30.0 kilogram per meter square (kg/m2) (inclusive) at the time of the&#xD;
             Screening examination.&#xD;
&#xD;
          -  A female participant is eligible to participate if she is not pregnant, not&#xD;
             breastfeeding.&#xD;
&#xD;
          -  Females must have a negative serum pregnancy test at Screening visit and at Day -1&#xD;
             before randomization/first dosing.&#xD;
&#xD;
          -  Men must agree to use a barrier method (specifically, male condom with or without&#xD;
             spermicide) and to have their female partners use a highly effective method of&#xD;
             contraception during the treatment period, and for at least 3 months after the last&#xD;
             IMP administration. Men must also refrain from donating sperm during this period.&#xD;
&#xD;
          -  Healthy as assessed by the Investigator with no clinically significant abnormality&#xD;
             identified on physical examination or laboratory evaluation and no active clinically&#xD;
             significant disorder, condition, infection or disease that would pose a risk to&#xD;
             subject safety or interfere with the trial evaluation, procedures, or completion.&#xD;
&#xD;
          -  Stable non-smokers for at least 3 months preceding Screening.&#xD;
&#xD;
          -  Must agree not to consume any alcohol during the treatment period of the trial.&#xD;
&#xD;
          -  Able and willing to give written informed consent and has signed the appropriate&#xD;
             written informed consent form, approved by the Investigator's Independent Ethics&#xD;
             Committee (IEC), prior to the performance of any trial activities.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of clinically relevant disease of any organ system, that may interfere with&#xD;
             the objectives of the trial or provide a risk to the health of the subject.&#xD;
&#xD;
          -  History of chronic or recurrent acute infection or any bacterial, viral, parasitic or&#xD;
             fungal infections within 30 days prior to Screening and at any time between Screening&#xD;
             and admission, or hospitalization due to infection within 6 months prior to Screening.&#xD;
&#xD;
          -  History of Herpes zoster within 12 months prior to Screening&#xD;
&#xD;
          -  History of drug hypersensitivity, ascertained or presumptive allergy/hypersensitivity&#xD;
             to the active drug substance and/or formulation ingredients; history of serious&#xD;
             allergic reactions leading to hospitalization or any other hypersensitivity reaction&#xD;
             in general, which may affect the safety of the subject and/or outcome of the trial per&#xD;
             the Investigator's discretion.&#xD;
&#xD;
          -  History of alcoholism or drug abuse within 2 years prior to Screening and the subject&#xD;
             is unwilling to abstain from alcohol and drug of abuse during the trial&#xD;
&#xD;
          -  Consumption of an average weekly intake of greater than (&gt;) 14 drinks/week for males&#xD;
             or &gt; 7 drinks/week for females. One drink is equivalent to (12 g alcohol) = 5 ounces&#xD;
             (150 milliliter (mL)) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of&#xD;
             40 Vol% distilled spirits.&#xD;
&#xD;
          -  Positive for drugs of abuse, nicotine/cotinine or alcohol at Screening or at&#xD;
             admission.&#xD;
&#xD;
          -  Supine systolic blood pressure &gt; 140 mmHg or less than (&lt;) 90 mmHg, diastolic blood&#xD;
             pressure &gt; 90 mmHg or &lt;50 and pulse rate &gt;100 or ≤ 50 bpm, at admission.&#xD;
&#xD;
          -  12-Lead ECG showing a QTcF &gt; 450 ms, PQ &gt; 200ms, or QRS &gt; 120 ms or other clinically&#xD;
             relevant abnormal findings&#xD;
      </textblock>
    </criteria>
    <gender>All</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>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>Merck KGaA, Darmstadt, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nuvisan GmbH</name>
      <address>
        <city>Neu-Ulm</city>
        <state>Bavaria</state>
        <zip>89231</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>July 20, 2018</last_update_submitted>
  <last_update_submitted_qc>July 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>M7583</keyword>
  <keyword>Healthy Subjects</keyword>
  <keyword>Cross-over</keyword>
  <pending_results>
    <submitted>November 27, 2018</submitted>
    <submission_canceled>December 5, 2018</submission_canceled>
  </pending_results>
  <!-- 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/NCT03297983
org study id: MS200662-0017
secondary id: 2017-001674-41
nct id: NCT03297983
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a Phase I study consisting of 2 parts: Part 1 aims to investigate the relative
      bioavailability of tablet formulation (test treatment) and Powder in capsule (PiC)
      formulation (reference treatment) of M7583 under fasted conditions. The aim of Part 2 is to
      determine and compare the single dose Pharmacokinetic (PK) profile of M7583 tablet under
      fasted and fed conditions to assess the food effect.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concnetration (AUC0-t) of M7583
time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
measure: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of M7583
time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
measure: Maximum Observed Drug Concentration (Cmax) of M7583
time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
measure: Occurrence of Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
time frame: Up to Week 6
measure: Occurrence of Subjects With TEAEs by Severity According to Qualitative Toxicity Scale Selected From National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
time frame: Up to Week 6
measure: Number of Subjects with Clinically Significant Change From Baseline in Laboratory Tests, Vital Sign and 12-lead Electrocardiogram (ECG) Findings
time frame: Up to Week 6
measure: Time to Reach the Maximum Plasma Concentration (tmax) of M7583
time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
measure: Terminal Rate Constant (λz) of M7583
time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
measure: Apparent Terminal Half-life (t1/2) of M7583
time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
measure: Total Body Clearance of Drug From Plasma Following Oral Administration (CL/f) of M7583
time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
measure: Apparent Volume of Distribution (Vz/f) of M7583
time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
measure: Area Under the M7583 Plasma Concentration-time Curve From Time Zero to 24 hours After Dosing (AUC0-24h)
time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
measure: Percentage of AUC0-∞ Obtained by Extrapolation (%AUCextra) of M7583
time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
measure: Relative Bioavailability of M7583 Tablet versus M7583 PIC (Frel,T/P)
time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
measure: Relative Bioavailability of M7583 Tablet Administered 30 Minutes After a Standard Breakfast Versus Tablet Administered After an Overnight Fast (Frel,Fed/Fasted)
time frame: pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0, and 36.0 hours post-dose on Day 1 in each period
arm group label: First M7583 Tablet:Fasted, Then PiC:Fasted, Then Tablet:Fed
arm group type: Experimental
arm group label: First M7583 PiC:Fasted, Then Tablet:Fasted, Then Tablet:Fed
arm group type: Experimental
intervention type: Drug
intervention name: M7583
description: Subject will receive either M7583 PiC or M7583 tablet formulation orally under fasted conditions in part 1 followed by M7583 tablet formulation under fed condition in part 2 of the study.
arm group label: First M7583 PiC:Fasted, Then Tablet:Fasted, Then Tablet:Fed
arm group label: First M7583 Tablet:Fasted, Then PiC:Fasted, Then Tablet:Fed
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Responsible
role: Study Director
affiliation: Merck KGaA, Darmstadt, Germany
facility: 
country: Germany
responsible party type: Sponsor
submitted: November 27, 2018
submission canceled: December 5, 2018