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

NCT04464239 | Completed Phase 1 FDA Drug

• 1 other identifier: TS142-US101
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

TS-142

Outcome Measures

Primary Outcomes (14)

• 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

Study Arms (3)

Part A: Cohort 1: TS-142 10 mg

EXPERIMENTAL

Single dose of TS-142 10 mg or placebo in a fasted condition

Drug: TS-142; Drug: TS-142 Placebo

Part A: Cohort 2: TS-142 30 mg

EXPERIMENTAL

Single dose of TS-142 30 mg or placebo in a fasted condition.

Drug: TS-142; Drug: TS-142 Placebo

Part B: Cohort 4: TS-142 20 mg

EXPERIMENTAL

Daily doses of 20 mg TS-142 or placebo for 7 days before bedtime.

Drug: TS-142; Drug: TS-142 Placebo

Interventions

TS-142 DRUG

TS-142 tablets

Part A: Cohort 1: TS-142 10 mg; Part A: Cohort 2: TS-142 30 mg; Part B: Cohort 4: TS-142 20 mg

TS-142 Placebo DRUG

TS-142 matching placebo tablets

Part A: Cohort 1: TS-142 10 mg; Part A: Cohort 2: TS-142 30 mg; Part B: Cohort 4: TS-142 20 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Taisho Pharmaceutical R&D Inc.: lead

Study Sites (1)

PPD Phase I unit

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

TS-142

Study Officials

• Taisho Director

  Taisho Pharmaceutical R&D Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2020
• First Posted: July 9, 2020
• Study Start: September 14, 2020
• Primary Completion: January 21, 2021
• Study Completion: January 21, 2021
• Last Updated: February 10, 2021

Record last verified: 2021-02

Locations

US (1)