<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/NCT04464239</url>
  </required_header>
  <id_info>
    <org_study_id>TS142-US101</org_study_id>
    <nct_id>NCT04464239</nct_id>
  </id_info>
  <brief_title>A Single Ascending and Repeated Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TS-142 in Healthy Participants</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled, Single Ascending and Repeated Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TS-142 Administered Orally to Healthy Male and Female Participants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Taisho Pharmaceutical R&amp;D Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Taisho Pharmaceutical R&amp;D Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a study to evaluate the safety, tolerability, and pharmacokinetics of single oral&#xD;
      doses of TS-142 compared to placebo and of a single repeated dose compared to placebo in&#xD;
      healthy volunteers. This Phase I study is composed of two parts; Part A (Single Ascending&#xD;
      Dose) and Part B (Repeated Dose). The study employs a randomized, double-blind,&#xD;
      placebo-controlled, parallel group design to evaluate the single and repeat-dose safety and&#xD;
      pharmacokinetics of TS-142 in healthy participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 14, 2020</start_date>
  <completion_date type="Actual">January 21, 2021</completion_date>
  <primary_completion_date type="Actual">January 21, 2021</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>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence and severity of Adverse Events</measure>
    <time_frame>Part A: Day 1 to Day 10; Part B: Day 1 to Day 16</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Plasma Pharmacokinetic Profile - Cmax</measure>
    <time_frame>Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose</time_frame>
    <description>Maximum plasma concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Plasma Pharmacokinetic Profile - Tmax</measure>
    <time_frame>Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose</time_frame>
    <description>Time to maximum plasma concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Plasma Pharmacokinetic Profile - AUC(0-∞)</measure>
    <time_frame>Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose</time_frame>
    <description>Area Under the Concentration vs. Time Curve from Time Zero to Infinity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Plasma Pharmacokinetic Profile - AUC(0-last)</measure>
    <time_frame>Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose</time_frame>
    <description>Area Under the Concentration vs. Time Curve from Time Zero to Last Measurable Concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Plasma Pharmacokinetic Profile - AUC(0-tau)</measure>
    <time_frame>Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose</time_frame>
    <description>Area Under the Concentration vs. Time Curve over a Dosing Interval</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Plasma Pharmacokinetic Profile - %AUCex</measure>
    <time_frame>Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose</time_frame>
    <description>Percentage of the area extrapolated for calculation of AUC(0-∞)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Plasma Pharmacokinetic Profile - λz</measure>
    <time_frame>Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose</time_frame>
    <description>Elimination rate constant</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Plasma Pharmacokinetic Profile - t1/2</measure>
    <time_frame>Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose</time_frame>
    <description>Apparent terminal half-life</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Plasma Pharmacokinetic Profile - CL/F</measure>
    <time_frame>Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose</time_frame>
    <description>Apparent oral clearance</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Plasma Pharmacokinetic Profile - Vd,z/F</measure>
    <time_frame>Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose</time_frame>
    <description>Volumes of distribution</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Urine Pharmacokinetic Profile - Ae</measure>
    <time_frame>Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose</time_frame>
    <description>Amount excreted in urine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Urine Pharmacokinetic Profile - Fe%</measure>
    <time_frame>Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose</time_frame>
    <description>Percent of dose excreted in urine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>TS-142 Urine Pharmacokinetic Profile - CLr</measure>
    <time_frame>Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose</time_frame>
    <description>Renal clearance</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Part A: Cohort 1: TS-142 10 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of TS-142 10 mg or placebo in a fasted condition</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A: Cohort 2: TS-142 30 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of TS-142 30 mg or placebo in a fasted condition.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Cohort 4: TS-142 20 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Daily doses of 20 mg TS-142 or placebo for 7 days before bedtime.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TS-142</intervention_name>
    <description>TS-142 tablets</description>
    <arm_group_label>Part A: Cohort 1: TS-142 10 mg</arm_group_label>
    <arm_group_label>Part A: Cohort 2: TS-142 30 mg</arm_group_label>
    <arm_group_label>Part B: Cohort 4: TS-142 20 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TS-142 Placebo</intervention_name>
    <description>TS-142 matching placebo tablets</description>
    <arm_group_label>Part A: Cohort 1: TS-142 10 mg</arm_group_label>
    <arm_group_label>Part A: Cohort 2: TS-142 30 mg</arm_group_label>
    <arm_group_label>Part B: Cohort 4: TS-142 20 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy adult male and female participants between 18 and 55 years of age, inclusive&#xD;
&#xD;
          -  Body weight ≥ 45 kg at screening and admission visits.&#xD;
&#xD;
          -  Body Mass Index (BMI) ≥ 18 and ≤ 30 kg/m^2 at screening visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically significant abnormal values for hematology, clinical chemistry or&#xD;
             urinalysis at the screening and/or admission visits.&#xD;
&#xD;
          -  Clinically significant abnormal physical examination (including neurological&#xD;
             assessments), vital signs, or 12-lead ECGs at the screening and/or admission visits.&#xD;
&#xD;
          -  QTcF &gt;450 msec for male participants or QTcF &gt;470 msec for female participants at the&#xD;
             screening and/or admission visits.&#xD;
&#xD;
          -  Significant history or presence of hepatic, renal, cardiovascular, pulmonary,&#xD;
             gastrointestinal, hematological, neurological, immunologic, ophthalmologic, metabolic&#xD;
             or oncological disease.&#xD;
&#xD;
          -  History or present diagnosis of sleep disorders.&#xD;
&#xD;
          -  Currently experiencing sleep disturbance related to postmenopausal symptoms at the&#xD;
             screening and/or admission visits.&#xD;
&#xD;
          -  History or presence of suicidal behavior, defined as participants who have answered&#xD;
             'YES' to any of the C-SSRS suicidal behavior questions at the screening and/or&#xD;
             admission visits.&#xD;
&#xD;
          -  Positive urine screen for alcohol or controlled substances at the screening or&#xD;
             admission visits.&#xD;
&#xD;
          -  Recent history (within the previous 6 months) of alcohol or drug abuse.&#xD;
&#xD;
          -  Regular alcohol consumption of &gt; 2 units/day or 10 units/week during the last 3 months&#xD;
             prior to screening. One unit is equivalent to 8 g of alcohol: a half pint (240 mL) of&#xD;
             beer, a glass (125 mL) of wine, or 25 mL of spirits.&#xD;
&#xD;
          -  Current use, or use of tobacco or tobacco-containing products (cigarettes, pipes,&#xD;
             e-cigarettes, nicotine patches, etc.) during the month prior to screening, or positive&#xD;
             urine cotinine screen (&gt;400 ng/mL) at the screening and/or admission visits.&#xD;
&#xD;
          -  History of and/or current evidence of serologic positive results for hepatitis B&#xD;
             surface antigen (HBsAg), hepatitis C antibodies, or human immunodeficiency virus (HIV)&#xD;
             antibodies 1 and 2.&#xD;
&#xD;
          -  Donation of one or more units of blood, plasma (including platelet donations), or&#xD;
             acute loss of an equivalent amount of blood within 60 days prior to screening visit&#xD;
             (one unit= 450 mL).&#xD;
&#xD;
          -  Exposure to any investigational product within 60 days prior to screening.&#xD;
&#xD;
          -  Use of any prescription or over-the-counter medication, herbal medication, vitamins,&#xD;
             or mineral supplements within 14 days prior to administration of the study drug.&#xD;
&#xD;
          -  Participants who regularly consume &gt;500 mg of caffeine on a daily basis.&#xD;
&#xD;
          -  Is known to be allergic to the study drug or any components of the study drug.&#xD;
&#xD;
          -  Participated in strenuous exercise within 48 hours prior to study start (initial&#xD;
             dosing) and/or is unwilling to avoid strenuous exercise at any time throughout the&#xD;
             study.&#xD;
&#xD;
          -  Participants who work night shifts or need to work night shifts during the trial.&#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>Taisho Director</last_name>
    <role>Study Director</role>
    <affiliation>Taisho Pharmaceutical R&amp;D Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PPD Phase I unit</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>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>February 5, 2021</last_update_submitted>
  <last_update_submitted_qc>February 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TS-142</keyword>
  <!-- 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/NCT04464239
org study id: TS142-US101
nct id: NCT04464239
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a study to evaluate the safety, tolerability, and pharmacokinetics of single oral
      doses of TS-142 compared to placebo and of a single repeated dose compared to placebo in
      healthy volunteers. This Phase I study is composed of two parts; Part A (Single Ascending
      Dose) and Part B (Repeated Dose). The study employs a randomized, double-blind,
      placebo-controlled, parallel group design to evaluate the single and repeat-dose safety and
      pharmacokinetics of TS-142 in healthy participants.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Incidence and severity of Adverse Events
time frame: Part A: Day 1 to Day 10; Part B: Day 1 to Day 16
measure: TS-142 Plasma Pharmacokinetic Profile - Cmax
time frame: Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose
description: Maximum plasma concentration
measure: TS-142 Plasma Pharmacokinetic Profile - Tmax
time frame: Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose
description: Time to maximum plasma concentration
measure: TS-142 Plasma Pharmacokinetic Profile - AUC(0-∞)
time frame: Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose
description: Area Under the Concentration vs. Time Curve from Time Zero to Infinity
measure: TS-142 Plasma Pharmacokinetic Profile - AUC(0-last)
time frame: Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose
description: Area Under the Concentration vs. Time Curve from Time Zero to Last Measurable Concentration
measure: TS-142 Plasma Pharmacokinetic Profile - AUC(0-tau)
time frame: Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose
description: Area Under the Concentration vs. Time Curve over a Dosing Interval
measure: TS-142 Plasma Pharmacokinetic Profile - %AUCex
time frame: Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose
description: Percentage of the area extrapolated for calculation of AUC(0-∞)
measure: TS-142 Plasma Pharmacokinetic Profile - λz
time frame: Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose
description: Elimination rate constant
measure: TS-142 Plasma Pharmacokinetic Profile - t1/2
time frame: Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose
description: Apparent terminal half-life
measure: TS-142 Plasma Pharmacokinetic Profile - CL/F
time frame: Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose
description: Apparent oral clearance
measure: TS-142 Plasma Pharmacokinetic Profile - Vd,z/F
time frame: Part A: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part B: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 6 predose, Day 7 predose and at multiple time points (up to 48 hours) postdose
description: Volumes of distribution
measure: TS-142 Urine Pharmacokinetic Profile - Ae
time frame: Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose
description: Amount excreted in urine
measure: TS-142 Urine Pharmacokinetic Profile - Fe%
time frame: Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose
description: Percent of dose excreted in urine
measure: TS-142 Urine Pharmacokinetic Profile - CLr
time frame: Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose
description: Renal clearance
arm group label: Part A: Cohort 1: TS-142 10 mg
arm group type: Experimental
description: Single dose of TS-142 10 mg or placebo in a fasted condition
arm group label: Part A: Cohort 2: TS-142 30 mg
arm group type: Experimental
description: Single dose of TS-142 30 mg or placebo in a fasted condition.
arm group label: Part B: Cohort 4: TS-142 20 mg
arm group type: Experimental
description: Daily doses of 20 mg TS-142 or placebo for 7 days before bedtime.
intervention type: Drug
intervention name: TS-142
description: TS-142 tablets
arm group label: Part A: Cohort 1: TS-142 10 mg
arm group label: Part A: Cohort 2: TS-142 30 mg
arm group label: Part B: Cohort 4: TS-142 20 mg
intervention type: Drug
intervention name: TS-142 Placebo
description: TS-142 matching placebo tablets
arm group label: Part A: Cohort 1: TS-142 10 mg
arm group label: Part A: Cohort 2: TS-142 30 mg
arm group label: Part B: Cohort 4: TS-142 20 mg
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Taisho Director
role: Study Director
affiliation: Taisho Pharmaceutical R&D Inc.
facility: 
country: United States
responsible party type: Sponsor