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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03919409
• Other study ID #: TS161-US101
• Status: Completed
• Phase: Phase 1
• Start date: June 3, 2019
• Est. completion date: February 11, 2020

Study information

• Verified date: February 2020
• Source: Taisho Pharmaceutical R&D Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: February 11, 2020
• Est. primary completion date: February 11, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

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

Locations

Country	Name	City	State
United States	PAREXEL - Early Phase Clinical Unit-Los Angeles	Glendale	California

Sponsors (1)

Lead Sponsor	Collaborator
Taisho Pharmaceutical R&D Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of Adverse Events		Parts A and B: Day 1 to Day 8; Part C: Day 1 to Day 17
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	TS-161 CSF Pharmacokinetic Profile - Cmax	Maximum CSF concentration	Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose
Secondary	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
Secondary	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
Secondary	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
Secondary	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