<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/NCT02232529</url>
  </required_header>
  <id_info>
    <org_study_id>MIN-101C02</org_study_id>
    <secondary_id>2014-001613-53</secondary_id>
    <nct_id>NCT02232529</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Study of MIN-101 in Healthy Subjects</brief_title>
  <official_title>A Two-Part Study Designed to Evaluate the Pharmacokinetic Profile of MIN-101 and Its Main Metabolites Following Single and Multiple Dose Modified Release Prototype Formulation Administration in Healthy Cytochrome P450 2D6 Extensive Metabolizer Male and Female Subjects, and to Evaluate the Relationship Between the Pharmacokinetic Profile of MIN-101 and Its Main Metabolites and Cardiovascular Parameters.</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>
      The aim of the study is to assess how MIN-101 is taken up by the body when given in different&#xD;
      amounts and in different formulations. The drug will be given as a single dose in Part 1 of&#xD;
      the study and during Part 2 of the study as multiple dose, once daily for 7 days. The&#xD;
      ultimate aim is to find an optimal formulation which can be developed as a once daily dose&#xD;
      for the treatment of schizophrenia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 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>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1 Pharmacokinetic profile of MIN-101 and its main metabolites (AUC (0-last), Tmax, Cmax, AUC (0-inf), %AUCextrap, Lambda z, T1/2 and parent:metabolites ratio</measure>
    <time_frame>predose and 0.5h, 1h, 1.5h, 2h, 2.5h, 3H, 4H, 6h, 8h, 10h, 12h, 14h, 16h, 20h, 24h, 48h and 72h post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2 - Pharmacokinetic profile of MIN-101 and its main metabolites - Absolute QT intervals and QT intervals corrected using Fridericia formula (QTcF)</measure>
    <time_frame>predose to Day 8</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1 Safety and tolerability (incidence of adverse events, safety laboratory, 12-lead ECGs, vital signs, physical examination) -</measure>
    <time_frame>from predose up to 72 h post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1 Pharmacokinetic profile of MIN-101 in fed and fasted state</measure>
    <time_frame>from predose up to 72 h post dosing</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2 Change from baseline in ECG parameters other than QT/QTc</measure>
    <time_frame>from predose up to Day 8</time_frame>
    <description>QTcB, QRS, RR, PR intervals, U waves, T waves morphology</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2 Change from baseline in heart rate and blood pressure</measure>
    <time_frame>from predose up to Day 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2 Incidence of QT/QTc changes from baseline greater than 30 and 60 ms post dose</measure>
    <time_frame>from predose up to Day 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2 Incidence of QTc values greater than 450, 480 and 500 ms post dose</measure>
    <time_frame>from predose up to Day 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2 Safety and tolerability of MIN-101 (adverse events occurrence, physical examination, safety laboratory tests)</measure>
    <time_frame>from predose up to Day 8</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in sleep architecture and sleep continuity</measure>
    <time_frame>Day 6</time_frame>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Part 1: MIN-101</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MIN-101&#xD;
modified release formulation (MR),single oral dose between 16 and 64 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: MIN-101 low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MIN-101&#xD;
single daily oral dose, low dose MR formulation, from Day 1 to Day 7</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo MIN-101&#xD;
daily oral dose from Day 1 to Day 7</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: MIN-101 high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MIN-101&#xD;
single daily oral dose, low dose MR formulation, from Day 1 to Day 7</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MIN-101</intervention_name>
    <arm_group_label>Part 1: MIN-101</arm_group_label>
    <arm_group_label>Part 2: MIN-101 high dose</arm_group_label>
    <arm_group_label>Part 2: MIN-101 low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Part 2: placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males (Part 1 and Part 2) or non-pregnant, non-lactating healthy females (Part&#xD;
             2 only)&#xD;
&#xD;
          -  Body mass index (BMI) of 18.0 to 30.0 kg/m2&#xD;
&#xD;
          -  Must be CYP2D6 Extensive metabolizer&#xD;
&#xD;
          -  Must be willing and able to communicate and participate in the whole study&#xD;
&#xD;
          -  Must provide written informed consent&#xD;
&#xD;
          -  Must agree to use an adequate method of contraception&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who have QTc &gt; 430 in male, &gt; 450 in female confirmed by a repeat ECG&#xD;
&#xD;
          -  Any family history of sudden cardiac death and Torsade de Points&#xD;
&#xD;
          -  No personal or family history of unexplained presyncope, syncope or orthostatic&#xD;
             hypotension&#xD;
&#xD;
          -  History of any drug or alcohol abuse in the past 2 years&#xD;
&#xD;
          -  History or evidence of any medically diagnosed clinically significant psychiatric&#xD;
             disorders&#xD;
&#xD;
          -  Suicidal tendencies or history of suicidal attempts&#xD;
&#xD;
          -  Regular alcohol consumption in males &gt;21 units per week and females &gt;14 units per week&#xD;
             (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)&#xD;
&#xD;
          -  Current smokers and those who have smoked within the last 12 months. A breath carbon&#xD;
             monoxide reading of greater than 10 ppm at screening&#xD;
&#xD;
          -  Females of childbearing potential who are pregnant or lactating (female subjects must&#xD;
             have a negative urine pregnancy test at admission)&#xD;
&#xD;
          -  Clinically significant abnormal biochemistry, haematology or urinalysis as judged by&#xD;
             the investigator&#xD;
&#xD;
          -  Positive drugs of abuse test result&#xD;
&#xD;
          -  Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or&#xD;
             human immunodeficiency virus (HIV) results&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pui Leung, M.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Quotient Clinical</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Quotient Clinical</name>
      <address>
        <city>Ruddington, Nottingham</city>
        <zip>NG116JS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>February 2015</verification_date>
  <study_first_submitted>September 3, 2014</study_first_submitted>
  <study_first_submitted_qc>September 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <last_update_submitted>February 23, 2015</last_update_submitted>
  <last_update_submitted_qc>February 23, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 24, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>modified release formulation</keyword>
  <keyword>pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_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/NCT02232529
org study id: MIN-101C02
secondary id: 2014-001613-53
nct id: NCT02232529
lead sponsor: 
has dmc: No
The aim of the study is to assess how MIN-101 is taken up by the body when given in different
      amounts and in different formulations. The drug will be given as a single dose in Part 1 of
      the study and during Part 2 of the study as multiple dose, once daily for 7 days. The
      ultimate aim is to find an optimal formulation which can be developed as a once daily dose
      for the treatment of schizophrenia.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
measure: Part 1 Pharmacokinetic profile of MIN-101 and its main metabolites (AUC (0-last), Tmax, Cmax, AUC (0-inf), %AUCextrap, Lambda z, T1/2 and parent:metabolites ratio
time frame: predose and 0.5h, 1h, 1.5h, 2h, 2.5h, 3H, 4H, 6h, 8h, 10h, 12h, 14h, 16h, 20h, 24h, 48h and 72h post-dose
measure: Part 2 - Pharmacokinetic profile of MIN-101 and its main metabolites - Absolute QT intervals and QT intervals corrected using Fridericia formula (QTcF)
time frame: predose to Day 8
measure: Part 1 Safety and tolerability (incidence of adverse events, safety laboratory, 12-lead ECGs, vital signs, physical examination) -
time frame: from predose up to 72 h post dosing
measure: Part 1 Pharmacokinetic profile of MIN-101 in fed and fasted state
time frame: from predose up to 72 h post dosing
measure: Part 2 Change from baseline in ECG parameters other than QT/QTc
time frame: from predose up to Day 8
description: QTcB, QRS, RR, PR intervals, U waves, T waves morphology
measure: Part 2 Change from baseline in heart rate and blood pressure
time frame: from predose up to Day 8
measure: Part 2 Incidence of QT/QTc changes from baseline greater than 30 and 60 ms post dose
time frame: from predose up to Day 8
measure: Part 2 Incidence of QTc values greater than 450, 480 and 500 ms post dose
time frame: from predose up to Day 8
measure: Part 2 Safety and tolerability of MIN-101 (adverse events occurrence, physical examination, safety laboratory tests)
time frame: from predose up to Day 8
measure: Changes in sleep architecture and sleep continuity
time frame: Day 6
arm group label: Part 1: MIN-101
arm group type: Experimental
description: MIN-101
modified release formulation (MR),single oral dose between 16 and 64 mg
arm group label: Part 2: MIN-101 low dose
arm group type: Experimental
description: MIN-101
single daily oral dose, low dose MR formulation, from Day 1 to Day 7
arm group label: Part 2: placebo
arm group type: Placebo Comparator
description: placebo MIN-101
daily oral dose from Day 1 to Day 7
arm group label: Part 2: MIN-101 high dose
arm group type: Experimental
description: MIN-101
single daily oral dose, low dose MR formulation, from Day 1 to Day 7
intervention type: Drug
intervention name: MIN-101
arm group label: Part 1: MIN-101
arm group label: Part 2: MIN-101 high dose
arm group label: Part 2: MIN-101 low dose
intervention type: Drug
intervention name: Placebo
arm group label: Part 2: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pui Leung, M.D
role: Principal Investigator
affiliation: Quotient Clinical
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Schizophrenia