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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04464239
• Other study ID #: TS142-US101
• Status: Completed
• Phase: Phase 1
• Start date: September 14, 2020
• Est. completion date: January 21, 2021

Study information

• Verified date: February 2021
• Source: Taisho Pharmaceutical R&D Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: January 21, 2021
• Est. primary completion date: January 21, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• TS-142
TS-142 tablets
• TS-142 Placebo
TS-142 matching placebo tablets

Locations

Country	Name	City	State
United States	PPD Phase I unit	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Taisho Pharmaceutical R&D Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of Adverse Events		Part A: Day 1 to Day 10; Part B: Day 1 to Day 16
Primary	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
Primary	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
Primary	TS-142 Plasma Pharmacokinetic Profile - AUC(0-8)	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
Primary	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
Primary	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
Primary	TS-142 Plasma Pharmacokinetic Profile - %AUCex	Percentage of the area extrapolated for calculation of AUC(0-8)	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
Primary	TS-142 Plasma Pharmacokinetic Profile - ?z	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	TS-142 Urine Pharmacokinetic Profile - CLr	Renal clearance	Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose