<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/NCT03038646</url>
  </required_header>
  <id_info>
    <org_study_id>MIN-101C06</org_study_id>
    <nct_id>NCT03038646</nct_id>
  </id_info>
  <brief_title>A Pharmacokinetic Study of Modified Release (MR) Formulations of MIN-101 in Healthy Subjects</brief_title>
  <official_title>A Phase 1, Open-Label, Randomised, 3-Treatment, 3-Period, Single-Dose, Crossover Study in Healthy Subjects to Compare the Pharmacokinetic Properties of Modified Release (MR) Formulations of MIN-101 Followed by Food Effect Testing of a Selected Formulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Minerva Neurosciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Minerva Neurosciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      -  To evaluate the pharmacokinetic (PK) profiles of MIN-l0l following administration of&#xD;
           modified release (MR) formulations of MIN-l0l in healthy male and female subjects&#xD;
&#xD;
        -  To select 1 MR formulation for use in fed state&#xD;
&#xD;
        -  To evaluate the effect of food on the bioavailability of MIN-l0l selected MR formulation&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 30, 2016</start_date>
  <completion_date type="Actual">April 20, 2017</completion_date>
  <primary_completion_date type="Actual">April 20, 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>Part 1: Plasma PK parameter, Cmax</measure>
    <time_frame>from predose up to 72 hours post dose: Blood samples for MIN-101 will be collected at time 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 48, 60, and 72 hours post-dose on Day 1 of all periods.</time_frame>
    <description>To estimate the relative bioavailability of MIN-l0l following MIN-101 administration. Plasma samples will be analyzed for MIN-101 and its metabolites using a validated LC-MS/MS method</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Plasma PK parameter, Tmax</measure>
    <time_frame>from predose up to 72 hours post dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Plasma PK parameter, Tlag</measure>
    <time_frame>from predose up to 72 hours post dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Plasma PK parameter,partial AUC (e.g., AUC12, AUC24), AUClast, AUC∞</measure>
    <time_frame>from predose up to 72 hours post dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Plasma PK parameter, λz and t1/2</measure>
    <time_frame>from predose up to 72 hours post dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Plasma PK parameter, Cmax</measure>
    <time_frame>from predose up to 72 hours post dose: Blood samples for MIN-101 will be collected at time 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 48, 60, and 72 hours post-dose on Day 1 of all periods.</time_frame>
    <description>To estimate the relative bioavailability of MIN-101 and its main metabolites following the administration of the selected modified release formulation in different food conditions (fasted or fed state).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Plasma PK parameter, Tmax</measure>
    <time_frame>from predose up to 72 hours post dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Plasma PK parameter, Tlag</measure>
    <time_frame>from predose up to 72 hours post dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Plasma PK parameter, λz and t1/2</measure>
    <time_frame>from predose up to 72 hours post dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1: QTcF changes from baseline</measure>
    <time_frame>from predose up to 72 hours post dose</time_frame>
    <description>The effect of coincidentally measured (time-matched) plasma concentrations of MIN-l0l on QTcF changes from Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Safety (AE reporting, safety laboratory parameters analysis, vital signs and 12 lead ECG assessments)</measure>
    <time_frame>2 months 16 days</time_frame>
    <description>Safety will be assessed through AE reporting, safety laboratory parameters analysis, vital signs and 12 lead ECG assessments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Safety (AE reporting, safety laboratory parameters analysis, vital signs and 12 lead ECG assessments)</measure>
    <time_frame>2 months 16 days</time_frame>
    <description>Safety will be assessed through AE reporting, safety laboratory parameters analysis, vital signs and 12 lead ECG assessments</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Healthy Subjects</condition>
  <arm_group>
    <arm_group_label>Regimen A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>32 mg MIN-101 of the current modified-release formulation (comparator) identified as MR-32 formulation administered in the fasted state</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regimen B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>32 mg MIN-101 MR administered in the fasted state</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regimen C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>32 mg MIN-101 MR administered in the fasted state</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 selected dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>32 mg MIN-101 of MR administered in the fed state</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MIN-101</intervention_name>
    <arm_group_label>Part 2 selected dose</arm_group_label>
    <arm_group_label>Regimen A</arm_group_label>
    <arm_group_label>Regimen B</arm_group_label>
    <arm_group_label>Regimen C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Confirmed CYP 2D6 extensive metaboliser genotype&#xD;
&#xD;
          2. Subject has given voluntary written informed consent before performance of any study&#xD;
             related procedure&#xD;
&#xD;
          3. Must be 18 to 45 years of age, inclusive&#xD;
&#xD;
          4. Subject must be a healthy male or female as indicated by the protocol&#xD;
&#xD;
          5. Agree to abstain from all medication (except for allowed birth control for 21 days&#xD;
             before the first dose with MIN-101&#xD;
&#xD;
          6. Subject agrees to use the methods of birth control as outlined in the protocol&#xD;
&#xD;
          7. Must be willing and able to communicate and participate in the whole study.&#xD;
&#xD;
          8. Willing to eat all the food supplied throughout the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. A history of clinically significant gastrointestinal disease, renal, hepatic,&#xD;
             neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic or psychiatric&#xD;
             disease or any other condition which, in the opinion of the principle investigator,&#xD;
             would jeopardize the safety of the subject or impact the validity of the study results&#xD;
&#xD;
          2. Acute diarrhoea or constipation in the 7 days before the predicted first study day.&#xD;
&#xD;
          3. Subject has donated blood within 90 days or plasma within 30 days of study dosing&#xD;
&#xD;
          4. Regular alcohol consumption in males&gt; 21 units per week and Females &gt; 14 units per&#xD;
             week (1 Unit = 1/2 pint beer, 25 mL of 40or a 125 mL glass of wine)&#xD;
&#xD;
          5. Subject has a borderline or long QTc Fridericia interval as defined by screening&#xD;
             readings of &gt;430 msec for males and &gt;440 for females or a personal or familial history&#xD;
             of long QT syndrome&#xD;
&#xD;
          6. Subject has participated in a clinical trial within 90 days prior to study initiation&#xD;
&#xD;
          7. Females who are pregnant or breast feeding&#xD;
&#xD;
          8. Subject has used any prescription medication or over-the-counter (OTC) medication,&#xD;
             including vitamin supplements, within 21 days prior to day l&#xD;
&#xD;
          9. Subject has been treated with any known P450 206 or 3A4 enzymes altering drugs within&#xD;
             30 days prior to the study&#xD;
&#xD;
         10. Subject has smoked or used nicotine products within 2 months prior to or during the&#xD;
             study&#xD;
&#xD;
         11. Subject has sought advice from or been referred to a GP or counsellor for abuse or&#xD;
             misuse of alcohol, non-medical drugs, medicinal drugs or other substance abuse, e.g.&#xD;
             solvents&#xD;
&#xD;
         12. Subject has a positive blood screen for HIV, Hepatitis B surface antigen (HBsAg), and&#xD;
             Hepatitis C Antibody&#xD;
&#xD;
         13. Any current or previous use of drugs such as opiates, cocaine, ecstasy, or intravenous&#xD;
             amphetamines and/or a positive urine screen for alcohol or drugs of abuse. Subjects&#xD;
             who admit to occasional past use of cannabis will not be excluded as long as they have&#xD;
             a negative drugs-of-abuse test and have been abstinent from cannabis use for at least&#xD;
             3 months&#xD;
&#xD;
         14. Subject has a current uncontrolled inter-current illness (i.e., active infection) or&#xD;
             has had a clinically significant illness within the last 30 days prior to Day 1&#xD;
&#xD;
         15. Subject has had major surgery within 28 days of study entry, or 12 months prior to&#xD;
             study for gastrointestinal surgery.&#xD;
&#xD;
         16. Failure to satisfy the investigator of fitness to participate for any other reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel Jabbari, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>BioKinetic Europe Ltd</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Biokinetic Europe</name>
      <address>
        <city>Belfast</city>
        <zip>BT2 7BA</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 1, 2017</study_first_posted>
  <last_update_submitted>August 30, 2017</last_update_submitted>
  <last_update_submitted_qc>August 30, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Food Effect</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03038646
org study id: MIN-101C06
nct id: NCT03038646
lead sponsor: 
has dmc: No
-  To evaluate the pharmacokinetic (PK) profiles of MIN-l0l following administration of
           modified release (MR) formulations of MIN-l0l in healthy male and female subjects

        -  To select 1 MR formulation for use in fed state

        -  To evaluate the effect of food on the bioavailability of MIN-l0l selected MR formulation
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Part 1: Plasma PK parameter, Cmax
time frame: from predose up to 72 hours post dose: Blood samples for MIN-101 will be collected at time 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 48, 60, and 72 hours post-dose on Day 1 of all periods.
description: To estimate the relative bioavailability of MIN-l0l following MIN-101 administration. Plasma samples will be analyzed for MIN-101 and its metabolites using a validated LC-MS/MS method
measure: Part 1: Plasma PK parameter, Tmax
time frame: from predose up to 72 hours post dose
measure: Part 1: Plasma PK parameter, Tlag
time frame: from predose up to 72 hours post dose
measure: Part 1: Plasma PK parameter,partial AUC (e.g., AUC12, AUC24), AUClast, AUC∞
time frame: from predose up to 72 hours post dose
measure: Part 1: Plasma PK parameter, λz and t1/2
time frame: from predose up to 72 hours post dose
measure: Part 2: Plasma PK parameter, Cmax
time frame: from predose up to 72 hours post dose: Blood samples for MIN-101 will be collected at time 0 (pre-dose), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 48, 60, and 72 hours post-dose on Day 1 of all periods.
description: To estimate the relative bioavailability of MIN-101 and its main metabolites following the administration of the selected modified release formulation in different food conditions (fasted or fed state).
measure: Part 2: Plasma PK parameter, Tmax
time frame: from predose up to 72 hours post dose
measure: Part 2: Plasma PK parameter, Tlag
time frame: from predose up to 72 hours post dose
measure: Part 2: Plasma PK parameter, λz and t1/2
time frame: from predose up to 72 hours post dose
measure: Part 1: QTcF changes from baseline
time frame: from predose up to 72 hours post dose
description: The effect of coincidentally measured (time-matched) plasma concentrations of MIN-l0l on QTcF changes from Baseline.
measure: Part 1: Safety (AE reporting, safety laboratory parameters analysis, vital signs and 12 lead ECG assessments)
time frame: 2 months 16 days
description: Safety will be assessed through AE reporting, safety laboratory parameters analysis, vital signs and 12 lead ECG assessments
measure: Part 2: Safety (AE reporting, safety laboratory parameters analysis, vital signs and 12 lead ECG assessments)
time frame: 2 months 16 days
description: Safety will be assessed through AE reporting, safety laboratory parameters analysis, vital signs and 12 lead ECG assessments
arm group label: Regimen A
arm group type: Experimental
description: 32 mg MIN-101 of the current modified-release formulation (comparator) identified as MR-32 formulation administered in the fasted state
arm group label: Regimen B
arm group type: Experimental
description: 32 mg MIN-101 MR administered in the fasted state
arm group label: Regimen C
arm group type: Experimental
description: 32 mg MIN-101 MR administered in the fasted state
arm group label: Part 2 selected dose
arm group type: Experimental
description: 32 mg MIN-101 of MR administered in the fed state
intervention type: Drug
intervention name: MIN-101
arm group label: Part 2 selected dose
arm group label: Regimen A
arm group label: Regimen B
arm group label: Regimen C
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Daniel Jabbari, MD
role: Principal Investigator
affiliation: BioKinetic Europe Ltd
facility: 
country: Ireland
responsible party type: Sponsor
sharing ipd: No