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

Sponsor
Taisho Pharmaceutical R&D Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03919409
Collaborator
(none)
70
Enrollment
1
Location
9
Arms
8.3
Actual Duration (Months)
8.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
70 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TS-161 Administered Orally to Healthy Male and Female Participants
Actual Study Start Date :
Jun 3, 2019
Actual Primary Completion Date :
Feb 11, 2020
Actual Study Completion Date :
Feb 11, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part A: Cohort 1: TS-161 15 mg

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

Drug: TS-161
TS-161 capsules

Drug: TS-161 Placebo
TS-161 matching placebo capsules
Experimental: Part A: Cohort 2: TS-161 50 mg

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
TS-161 capsules

Drug: TS-161 Placebo
TS-161 matching placebo capsules
Experimental: Part A: Cohort 3: TS-161 100 mg

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
TS-161 capsules

Drug: TS-161 Placebo
TS-161 matching placebo capsules
Experimental: Part A: Cohort 4: TS-161 200 mg

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
TS-161 capsules

Drug: TS-161 Placebo
TS-161 matching placebo capsules
Experimental: Part A: Cohort 5: TS-161 400 mg

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
TS-161 capsules

Drug: TS-161 Placebo
TS-161 matching placebo capsules
Experimental: Part B: Cohort 6: TS-161 TBD

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
TS-161 capsules
Experimental: Part C: Cohort 7: TS-161 TBD

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
TS-161 capsules

Drug: TS-161 Placebo
TS-161 matching placebo capsules
Experimental: Part C: Cohort 8: TS-161 TBD

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
TS-161 capsules

Drug: TS-161 Placebo
TS-161 matching placebo capsules
Experimental: Part C: Cohort 9: TS-161 TBD

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
TS-161 capsules

Drug: TS-161 Placebo
TS-161 matching placebo capsules

Outcome Measures

Primary Outcome Measures

  1. Incidence and severity of Adverse Events [Parts A and B: Day 1 to Day 8; Part C: Day 1 to Day 17]

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

Secondary Outcome Measures

  1. TS-161 CSF Pharmacokinetic Profile - Cmax [Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose]

    Maximum CSF concentration

  2. 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

  3. 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

  4. 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

  5. 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 PAREXEL - Early Phase Clinical Unit-Los Angeles Glendale California United States 91206

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.
Responsible Party:
Taisho Pharmaceutical R&D Inc.
ClinicalTrials.gov Identifier:
NCT03919409
Other Study ID Numbers:
  • TS161-US101
First Posted:
Apr 18, 2019
Last Update Posted:
Feb 28, 2020
Last Verified:
Feb 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Taisho Pharmaceutical R&D Inc.
TS-161
CSF
first-in-human

Study Results

No Results Posted as of Feb 28, 2020