First-in-Human Study With Single and Multiple Doses of TS-161 in Healthy Participants

NCT03919409 | Completed Phase 1 FDA Drug

• 1 other identifier: TS161-US101
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

TS-161; CSF; first-in-human

Outcome Measures

Primary Outcomes (11)

• 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

  Maximum plasma concentration

  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

• TS-161 Plasma Pharmacokinetic Profile - Tmax

  Time to maximum plasma concentration

  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

• TS-161 Plasma Pharmacokinetic Profile - AUC(0-last)

  Area under the plasma concentration versus time curve from time zero to last measurable concentration

  Parts A and B: Day 1 predose and at multiple time points (up to 48 hours) postdose

• TS-161 Plasma Pharmacokinetic Profile - AUC(0-tau)

  Area under the plasma concentration versus time curve over a dosing interval

  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

• TS-161 Plasma Pharmacokinetic Profile - T1/2

  Apparent terminal elimination half-life

  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

• TS-161 Plasma Pharmacokinetic Profile - CL/F

  Apparent clearance following oral administration

  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

• TS-161 Plasma Pharmacokinetic Profile - Vd,z/F

  Apparent volume of distribution following oral administration

  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

• TS-161 Urine Pharmacokinetic Profile - Ae

  Amount excreted in urine

  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

• TS-161 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; Part C: Day 1 predose and pooled for multiple intervals (up to 48 hours after last dose) postdose

• TS-161 Urine Pharmacokinetic Profile - CLr

  Renal Clearance

  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

Secondary Outcomes (5)

• TS-161 CSF Pharmacokinetic Profile - Cmax

  Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose

• TS-161 CSF Pharmacokinetic Profile - Tmax

  Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose

• TS-161 CSF Pharmacokinetic Profile - AUC(0-last)

  Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose

• TS-161 CSF Pharmacokinetic Profile - T1/2

  Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose

• 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

Study Arms (9)

Part A: Cohort 1: TS-161 15 mg

EXPERIMENTAL

Single dose of TS-161 15 mg or placebo in a fasted condition.

Drug: TS-161; Drug: TS-161 Placebo

Part A: Cohort 2: TS-161 50 mg

EXPERIMENTAL

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.

Drug: TS-161; Drug: TS-161 Placebo

Part A: Cohort 3: TS-161 100 mg

EXPERIMENTAL

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.

Drug: TS-161; Drug: TS-161 Placebo

Part A: Cohort 4: TS-161 200 mg

EXPERIMENTAL

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.

Drug: TS-161; Drug: TS-161 Placebo

Part A: Cohort 5: TS-161 400 mg

EXPERIMENTAL

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.

Drug: TS-161; Drug: TS-161 Placebo

Part B: Cohort 6: TS-161 TBD

EXPERIMENTAL

Single dose of TS-161 in a fasted condition. The dose level will be determined based on the results from the preceding cohorts.

Drug: TS-161

Part C: Cohort 7: TS-161 TBD

EXPERIMENTAL

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.

Drug: TS-161; Drug: TS-161 Placebo

Part C: Cohort 8: TS-161 TBD

EXPERIMENTAL

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.

Drug: TS-161; Drug: TS-161 Placebo

Part C: Cohort 9: TS-161 TBD

EXPERIMENTAL

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.

Drug: TS-161; Drug: TS-161 Placebo

Interventions

TS-161 DRUG

TS-161 capsules

Part A: Cohort 1: TS-161 15 mg; Part A: Cohort 2: TS-161 50 mg; Part A: Cohort 3: TS-161 100 mg; Part A: Cohort 4: TS-161 200 mg; Part A: Cohort 5: TS-161 400 mg; Part B: Cohort 6: TS-161 TBD; Part C: Cohort 7: TS-161 TBD; Part C: Cohort 8: TS-161 TBD; Part C: Cohort 9: TS-161 TBD

TS-161 Placebo DRUG

TS-161 matching placebo capsules

Part A: Cohort 1: TS-161 15 mg; Part A: Cohort 2: TS-161 50 mg; Part A: Cohort 3: TS-161 100 mg; Part A: Cohort 4: TS-161 200 mg; Part A: Cohort 5: TS-161 400 mg; Part C: Cohort 7: TS-161 TBD; Part C: Cohort 8: TS-161 TBD; Part C: Cohort 9: TS-161 TBD

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• Significant abnormalities in lumbar spine

Sponsors & Collaborators

• Taisho Pharmaceutical R&D Inc.: lead

Study Sites (1)

PAREXEL - Early Phase Clinical Unit-Los Angeles

Glendale, California, 91206, United States

Location

Study Officials

• Taisho Director

  Taisho Pharmaceutical R&D Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: April 18, 2019
• Study Start: June 3, 2019
• Primary Completion: February 11, 2020
• Study Completion: February 11, 2020
• Last Updated: February 28, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)