A Single Ascending and Repeated Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TS-142 in Healthy Participants

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: TS-142
* Drug: TS-142 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult male and female participants between 18 and 55 years of age, inclusive Body weight ≥ 45 kg at screening and admission visits. Body Mass Index (BMI) ≥ 18 and ≤ 30 kg/m^2 at screening visit. Exclusion Criteria: Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at the screening and/or admission visits. Clinically significant abnormal physical examination (including neurological assessments), vital signs, or 12-lead ECGs at the screening and/or admission visits. QTcF >450 msec for male participants or QTcF >470 msec for female participants at the screening and/or admission visits. Significant history or presence of hepatic, renal, cardiovascular, pulmonary, gastrointestinal, hematological, neurological, immunologic, ophthalmologic, metabolic or oncological disease. History or present diagnosis of sleep disorders. Currently experiencing sleep disturbance related to postmenopausal symptoms at the screening and/or admission visits. History or presence of suicidal behavior, defined as participants who have answered 'YES' to any of the C-SSRS suicidal behavior questions at the screening and/or admission visits. Positive urine screen for alcohol or controlled substances at the screening or admission visits. Recent history (within the previous 6 months) of alcohol or drug abuse. Regular alcohol consumption of > 2 units/day or 10 units/week during the last 3 months prior to screening. One unit is equivalent to 8 g of alcohol: a half pint (240 mL) of beer, a glass (125 mL) of wine, or 25 mL of spirits. Current use, or use of tobacco or tobacco-containing products (cigarettes, pipes, e-cigarettes, nicotine patches, etc.) during the month prior to screening, or positive urine cotinine screen (>400 ng/mL) at the screening and/or admission visits. History of and/or current evidence of serologic positive results for hepatitis B surface antigen (HBsAg), hepatitis C antibodies, or human immunodeficiency virus (HIV) antibodies 1 and 2. Donation of one or more units of blood, plasma (including platelet donations), or acute loss of an equivalent amount of blood within 60 days prior to screening visit (one unit= 450 mL). Exposure to any investigational product within 60 days prior to screening. Use of any prescription or over-the-counter medication, herbal medication, vitamins, or mineral supplements within 14 days prior to administration of the study drug. Participants who regularly consume >500 mg of caffeine on a daily basis. Is known to be allergic to the study drug or any components of the study drug. Participated in strenuous exercise within 48 hours prior to study start (initial dosing) and/or is unwilling to avoid strenuous exercise at any time throughout the study. Participants who work night shifts or need to work night shifts during the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Cohort 1: TS-142 10 mg<br>Single dose of TS-142 10 mg or placebo in a fasted condition | Drug: TS-142<br>* TS-142 tablets<br>Drug: TS-142 Placebo<br>* TS-142 matching placebo tablets<br>|
| Experimental: Part A: Cohort 2: TS-142 30 mg<br>Single dose of TS-142 30 mg or placebo in a fasted condition. | Drug: TS-142<br>* TS-142 tablets<br>Drug: TS-142 Placebo<br>* TS-142 matching placebo tablets<br>|
| Experimental: Part B: Cohort 4: TS-142 20 mg<br>Daily doses of 20 mg TS-142 or placebo for 7 days before bedtime. | Drug: TS-142<br>* TS-142 tablets<br>Drug: TS-142 Placebo<br>* TS-142 matching placebo tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of Adverse Events |  | Part A: Day 1 to Day 10; Part B: Day 1 to Day 16 | 
| TS-142 Plasma Pharmacokinetic Profile - Cmax | Maximum plasma concentration | 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 | 
| TS-142 Plasma Pharmacokinetic Profile - Tmax | Time to maximum plasma concentration | 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 | 
| TS-142 Plasma Pharmacokinetic Profile - AUC(0-∞) | Area Under the Concentration vs. Time Curve from Time Zero to Infinity | 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 | 
| TS-142 Plasma Pharmacokinetic Profile - AUC(0-last) | Area Under the Concentration vs. Time Curve from Time Zero to Last Measurable Concentration | 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 | 
| TS-142 Plasma Pharmacokinetic Profile - AUC(0-tau) | Area Under the Concentration vs. Time Curve over a Dosing Interval | 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 | 
| TS-142 Plasma Pharmacokinetic Profile - %AUCex | Percentage of the area extrapolated for calculation of AUC(0-∞) | 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 | 
| TS-142 Plasma Pharmacokinetic Profile - λz | Elimination rate constant | 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 | 
| TS-142 Plasma Pharmacokinetic Profile - t1/2 | Apparent terminal half-life | 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 | 
| TS-142 Plasma Pharmacokinetic Profile - CL/F | Apparent oral clearance | 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 | 
| TS-142 Plasma Pharmacokinetic Profile - Vd,z/F | Volumes of distribution | 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 | 
| TS-142 Urine Pharmacokinetic Profile - Ae | Amount excreted in urine | Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose | 
| TS-142 Urine Pharmacokinetic Profile - Fe% | Percent of dose excreted in urine | Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose | 
| TS-142 Urine Pharmacokinetic Profile - CLr | Renal clearance | Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TS-142