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

Taisho Pharmaceutical R&D Inc.28 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Healthy Volunteers

Interventions

TS-142DRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Incidence and severity of Adverse Events

Time frame: Part A: Day 1 to Day 10; Part B: Day 1 to Day 16

TS-142 Plasma Pharmacokinetic Profile - Cmax

Maximum plasma concentration

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

TS-142 Plasma Pharmacokinetic Profile - Tmax

Time to maximum plasma concentration

TS-142 Plasma Pharmacokinetic Profile - AUC(0-∞)

Area Under the Concentration vs. Time Curve from Time Zero to Infinity

TS-142 Plasma Pharmacokinetic Profile - AUC(0-last)

Area Under the Concentration vs. Time Curve from Time Zero to Last Measurable Concentration

TS-142 Plasma Pharmacokinetic Profile - AUC(0-tau)

Area Under the Concentration vs. Time Curve over a Dosing Interval

TS-142 Plasma Pharmacokinetic Profile - %AUCex

Percentage of the area extrapolated for calculation of AUC(0-∞)

TS-142 Plasma Pharmacokinetic Profile - λz

Elimination rate constant

TS-142 Plasma Pharmacokinetic Profile - t1/2

Apparent terminal half-life

TS-142 Plasma Pharmacokinetic Profile - CL/F

Apparent oral clearance

TS-142 Plasma Pharmacokinetic Profile - Vd,z/F

Volumes of distribution

TS-142 Urine Pharmacokinetic Profile - Ae

Amount excreted in urine

Time frame: 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

Time frame: Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose

TS-142 Urine Pharmacokinetic Profile - CLr

Renal clearance

Time frame: Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes