A Single Ascending and Repeated Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TS-142 in Healthy Participants
- Registration Number
- NCT04464239
- Lead Sponsor
- Taisho Pharmaceutical R&D Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Cohort 2: TS-142 30 mg TS-142 Single dose of TS-142 30 mg or placebo in a fasted condition. Part B: Cohort 4: TS-142 20 mg TS-142 Daily doses of 20 mg TS-142 or placebo for 7 days before bedtime. Part A: Cohort 2: TS-142 30 mg TS-142 Placebo Single dose of TS-142 30 mg or placebo in a fasted condition. Part A: Cohort 1: TS-142 10 mg TS-142 Single dose of TS-142 10 mg or placebo in a fasted condition Part B: Cohort 4: TS-142 20 mg TS-142 Placebo Daily doses of 20 mg TS-142 or placebo for 7 days before bedtime. Part A: Cohort 1: TS-142 10 mg TS-142 Placebo Single dose of TS-142 10 mg or placebo in a fasted condition
- Primary Outcome Measures
Name Time Method TS-142 Plasma Pharmacokinetic Profile - Tmax 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 to maximum plasma concentration
TS-142 Plasma Pharmacokinetic Profile - 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 Area Under the Concentration vs. Time Curve from Time Zero to Infinity
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 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 Maximum plasma concentration
TS-142 Urine Pharmacokinetic Profile - CLr Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose Renal clearance
TS-142 Plasma Pharmacokinetic Profile - AUC(0-last) 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 Area Under the Concentration vs. Time Curve from Time Zero to Last Measurable Concentration
TS-142 Plasma Pharmacokinetic Profile - AUC(0-tau) 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 Area Under the Concentration vs. Time Curve over a Dosing Interval
TS-142 Plasma Pharmacokinetic Profile - %AUCex 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 Percentage of the area extrapolated for calculation of AUC(0-∞)
TS-142 Plasma Pharmacokinetic Profile - λz 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 Elimination rate constant
TS-142 Plasma Pharmacokinetic Profile - t1/2 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 Apparent terminal half-life
TS-142 Plasma Pharmacokinetic Profile - CL/F 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 Apparent oral clearance
TS-142 Plasma Pharmacokinetic Profile - Vd,z/F 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 Volumes of distribution
TS-142 Urine Pharmacokinetic Profile - Ae Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose Amount excreted in urine
TS-142 Urine Pharmacokinetic Profile - Fe% Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose Percent of dose excreted in urine
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
PPD Phase I unit
🇺🇸Austin, Texas, United States