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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TS-161; Drug: TS-161 Placebo

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • PAREXEL - Early Phase Clinical Unit-Los Angeles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
TS-161 CSF Pharmacokinetic Profile - Cmax	Maximum CSF concentration	Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose
TS-161 CSF Pharmacokinetic Profile - Tmax	Time to maximum CSF concentration	Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose
TS-161 CSF Pharmacokinetic Profile - AUC(0-last)	Area under the CSF concentration versus time curve from time zero to last	Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose
TS-161 CSF Pharmacokinetic Profile - T1/2	Apparent terminal elimination half-life	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

Collaborators and Investigators

• Sponsor: Taisho Pharmaceutical R&D Inc.
• Investigators: Study Director: Taisho Director, Taisho Pharmaceutical R&D Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2019
• Primary Completion (Actual): February 11, 2020
• Study Completion (Actual): February 11, 2020

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: April 15, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): February 28, 2020
• Last Update Submitted That Met QC Criteria: February 26, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: first-in-human; CSF; TS-161
• Other Study ID Numbers: TS161-US101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No