Clinical trial NCT04464239: A Single Ascending and Repeated Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TS-142 in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: TS-142
Lead sponsor: Taisho Pharmaceutical R&D Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-09
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence and severity of Adverse Events
timeFrame: Part A: Day 1 to Day 10; Part B: Day 1 to Day 16
measure: TS-142 Plasma Pharmacokinetic Profile - Cmax
timeFrame: 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
measure: TS-142 Plasma Pharmacokinetic Profile - Tmax
timeFrame: 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
measure: TS-142 Plasma Pharmacokinetic Profile - AUC(0-∞)
timeFrame: 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
measure: TS-142 Plasma Pharmacokinetic Profile - AUC(0-last)
timeFrame: 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
measure: TS-142 Plasma Pharmacokinetic Profile - AUC(0-tau)
timeFrame: 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
measure: TS-142 Plasma Pharmacokinetic Profile - %AUCex
timeFrame: 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
measure: TS-142 Plasma Pharmacokinetic Profile - λz
timeFrame: 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
measure: TS-142 Plasma Pharmacokinetic Profile - t1/2
timeFrame: 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
measure: TS-142 Plasma Pharmacokinetic Profile - CL/F
timeFrame: 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
measure: TS-142 Plasma Pharmacokinetic Profile - Vd,z/F
timeFrame: 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
measure: TS-142 Urine Pharmacokinetic Profile - Ae
timeFrame: Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose
measure: TS-142 Urine Pharmacokinetic Profile - Fe%
timeFrame: Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose
measure: TS-142 Urine Pharmacokinetic Profile - CLr
timeFrame: Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose
Secondary outcomes:
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD Phase I unit
state: Texas
Study officials:
affiliation: Taisho Pharmaceutical R&D Inc.
name: Taisho Director
role: STUDY_DIRECTOR
References: