A Single Ascending and Repeated Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TS-142 in Healthy Participants
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A: Cohort 1: TS-142 10 mg Single dose of TS-142 10 mg or placebo in a fasted condition |
Drug: TS-142
TS-142 tablets
Drug: TS-142 Placebo
TS-142 matching placebo tablets
|
| Experimental: Part A: Cohort 2: TS-142 30 mg Single dose of TS-142 30 mg or placebo in a fasted condition. |
Drug: TS-142
TS-142 tablets
Drug: TS-142 Placebo
TS-142 matching placebo tablets
|
| Experimental: Part B: Cohort 4: TS-142 20 mg Daily doses of 20 mg TS-142 or placebo for 7 days before bedtime. |
Drug: TS-142
TS-142 tablets
Drug: TS-142 Placebo
TS-142 matching placebo tablets
|
Outcome Measures
Primary Outcome Measures
- 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 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
- 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
- TS-142 Urine Pharmacokinetic Profile - CLr [Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose]
Renal clearance
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | PPD Phase I unit | Austin | Texas | United States | 78744 |
Sponsors and Collaborators
- Taisho Pharmaceutical R&D Inc.
Investigators
- Study Director: Taisho Director, Taisho Pharmaceutical R&D Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TS142-US101