First-in-Human Study With Single and Multiple Doses of TS-161 in Healthy Participants
- Registration Number
- NCT03919409
- Lead Sponsor
- Taisho Pharmaceutical R&D Inc.
- Brief Summary
This is a Phase 1, first-in-human study involving single and multiple oral doses of TS-161 in healthy male and female participants. The safety, tolerability, pharmacokinetics and pharmacodynamics of TS-161 will be evaluated.
The study includes 3 parts; Part A (single ascending dose: Cohorts 1 to 5) , Part B (single dose, cerebrospinal fluid \[CSF\] collection: Cohort 6), and Part C (multiple ascending dose: Cohorts 7 to 9). Participants will be assigned to one of the 9 Cohorts.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 70
Inclusion Criteria
- Healthy adult male and female participants between 18 and 55 years of age, inclusive
- Body weight ≥ 45 kg
- Body Mass Index (BMI) 18 - 30 kg/m^2, inclusive
Exclusion Criteria
- Significant history or presence of medical disorders or condition capable of significantly affecting the absorption, metabolism, or elimination of drugs
- History or presence of psychiatric or neurologic disease or condition
- History of seizures
- Abnormal EEG observed at screening
- Abnormal blood pressure
- Breast cancer within the past 10 years, or any other malignancies within the past 5 years
- Clinically significant abnormal results in electrocardiogram, blood and urine test
- History or presence of liver disease
- Participants using medication or supplements within 14 days prior to dosing
- Use of N-methyl-D-aspartate (NMDA) receptor modulators (example: dextromethorphan, ketamine, amantadine, memantine) within 90 days of screening
- Loss of blood or blood products in excess of 450 mL within 60 days prior to screening
- Used any investigational drug within 60 days prior to screening
- Recent history of alcohol or drug abuse
- Any participant who currently uses or has used tobacco products or nicotine-containing products (cigarettes, pipes, e-cigarettes, nicotine patches, etc.) for one month or more prior to screening
Exclusion Criteria for Part B only:
- Significant abnormalities in lumbar spine
- History of clinically significant back pain, back pathology, and/or back injury
- History of migraines, and/or frequent, severe headaches
- History or presence of significant active bleeding or coagulation disorder or use of non-steroidal anti-inflammatory drugs or other drugs that affect coagulation or platelet function within 14 days prior to lumbar catheter insertion
- Allergy to lidocaine (Xylocaine®) or related drugs
- History of adverse reaction to lumbar puncture or epidural procedure
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Cohort 1: TS-161 15 mg TS-161 Single dose of TS-161 15 mg or placebo in a fasted condition. Part A: Cohort 3: TS-161 100 mg TS-161 Placebo Single dose of TS-161 100 mg or placebo in a fasted condition. Although planned, all subsequent dose levels after Cohort 1 will be determined based on the results from the preceding cohorts. Part C: Cohort 7: TS-161 TBD TS-161 Daily doses of TS-161 or placebo for 10 days in a fed condition. The dose level will be determined based on the results from the preceding cohorts. Part A: Cohort 4: TS-161 200 mg TS-161 Single dose of TS-161 200 mg or placebo in a fasted condition. Although planned, all subsequent dose levels after Cohort 1 will be determined based on the results from the preceding cohorts. Part A: Cohort 4: TS-161 200 mg TS-161 Placebo Single dose of TS-161 200 mg or placebo in a fasted condition. Although planned, all subsequent dose levels after Cohort 1 will be determined based on the results from the preceding cohorts. Part A: Cohort 5: TS-161 400 mg TS-161 Placebo Single dose of TS-161 400 mg or placebo in a fasted condition. Although planned, all subsequent dose levels after Cohort 1 will be determined based on the results from the preceding cohorts. Part A: Cohort 1: TS-161 15 mg TS-161 Placebo Single dose of TS-161 15 mg or placebo in a fasted condition. Part A: Cohort 2: TS-161 50 mg TS-161 Single dose of TS-161 50 mg or placebo which will be dosed first in a fasted condition, and then in a fed condition, with a washout period in between 2 dosing. Although planned, all subsequent dose levels after Cohort 1 will be determined based on the results from the preceding cohorts. Part A: Cohort 3: TS-161 100 mg TS-161 Single dose of TS-161 100 mg or placebo in a fasted condition. Although planned, all subsequent dose levels after Cohort 1 will be determined based on the results from the preceding cohorts. Part C: Cohort 8: TS-161 TBD TS-161 Placebo Daily doses of TS-161 or placebo for 10 days in a fed condition. The dose level will be determined based on the results from the preceding cohorts. Part A: Cohort 2: TS-161 50 mg TS-161 Placebo Single dose of TS-161 50 mg or placebo which will be dosed first in a fasted condition, and then in a fed condition, with a washout period in between 2 dosing. Although planned, all subsequent dose levels after Cohort 1 will be determined based on the results from the preceding cohorts. Part C: Cohort 7: TS-161 TBD TS-161 Placebo Daily doses of TS-161 or placebo for 10 days in a fed condition. The dose level will be determined based on the results from the preceding cohorts. Part C: Cohort 9: TS-161 TBD TS-161 Placebo Daily doses of TS-161 or placebo for 10 days in a fed condition. The dose level will be determined based on the results from the preceding cohorts. Part A: Cohort 5: TS-161 400 mg TS-161 Single dose of TS-161 400 mg or placebo in a fasted condition. Although planned, all subsequent dose levels after Cohort 1 will be determined based on the results from the preceding cohorts. Part C: Cohort 8: TS-161 TBD TS-161 Daily doses of TS-161 or placebo for 10 days in a fed condition. The dose level will be determined based on the results from the preceding cohorts. Part C: Cohort 9: TS-161 TBD TS-161 Daily doses of TS-161 or placebo for 10 days in a fed condition. The dose level will be determined based on the results from the preceding cohorts. Part B: Cohort 6: TS-161 TBD TS-161 Single dose of TS-161 in a fasted condition. The dose level will be determined based on the results from the preceding cohorts.
- Primary Outcome Measures
Name Time Method TS-161 Plasma Pharmacokinetic Profile - Tmax Parts A and B: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part C: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 9 predose, Day 10 predose and at multiple time points (up to 48 hours) postdose Time to maximum plasma concentration
Incidence and severity of Adverse Events Parts A and B: Day 1 to Day 8; Part C: Day 1 to Day 17 TS-161 Plasma Pharmacokinetic Profile - Cmax Parts A and B: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part C: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 9 predose, Day 10 predose and at multiple time points (up to 48 hours) postdose Maximum plasma concentration
TS-161 Plasma Pharmacokinetic Profile - AUC(0-tau) Part C: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 9 predose, Day 10 predose and at multiple time points (up to 48 hours) postdose Area under the plasma concentration versus time curve over a dosing interval
TS-161 Plasma Pharmacokinetic Profile - T1/2 Parts A and B: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part C: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 9 predose, Day 10 predose and at multiple time points (up to 48 hours) postdose Apparent terminal elimination half-life
TS-161 Plasma Pharmacokinetic Profile - Vd,z/F Parts A and B: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part C: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 9 predose, Day 10 predose and at multiple time points (up to 48 hours) postdose Apparent volume of distribution following oral administration
TS-161 Urine Pharmacokinetic Profile - Fe% Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose; Part C: Day 1 predose and pooled for multiple intervals (up to 48 hours after last dose) postdose Percent of dose excreted in urine
TS-161 Urine Pharmacokinetic Profile - CLr Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose; Part C: Day 1 predose and pooled for multiple intervals (up to 48 hours after last dose) postdose Renal Clearance
TS-161 Plasma Pharmacokinetic Profile - CL/F Parts A and B: Day 1 predose and at multiple time points (up to 48 hours) postdose; Part C: Day 1 predose and at multiple time points (up to 12 hours) postdose, Day 2 to Day 9 predose, Day 10 predose and at multiple time points (up to 48 hours) postdose Apparent clearance following oral administration
TS-161 Urine Pharmacokinetic Profile - Ae Part A: Day 1 predose and pooled for multiple intervals (up to 48 hours) postdose; Part C: Day 1 predose and pooled for multiple intervals (up to 48 hours after last dose) postdose Amount excreted in urine
TS-161 Plasma Pharmacokinetic Profile - AUC(0-last) Parts A and B: Day 1 predose and at multiple time points (up to 48 hours) postdose Area under the plasma concentration versus time curve from time zero to last measurable concentration
- Secondary Outcome Measures
Name Time Method TS-161 CSF Pharmacokinetic Profile - Tmax Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose Time to maximum CSF concentration
TS-161 CSF Pharmacokinetic Profile - Cmax Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose Maximum CSF concentration
TS-161 CSF Pharmacokinetic Profile - AUC(0-last) Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose Area under the CSF concentration versus time curve from time zero to last
TS-161 CSF Pharmacokinetic Profile - T1/2 Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose Apparent terminal elimination half-life
Changes from baseline in relative and absolute powers of the delta, theta, alpha, beta and gamma bands using quantitative electroencephalogram (qEEG) compared to placebo Part A: predose and at multiple time points (up to 8 hours) postdose
Trial Locations
- Locations (1)
PAREXEL - Early Phase Clinical Unit-Los Angeles
🇺🇸Glendale, California, United States
PAREXEL - Early Phase Clinical Unit-Los Angeles🇺🇸Glendale, California, United States