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

Taisho Pharmaceutical

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03919409

TS161-US101

Details and patient eligibility

About

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.

Enrollment: 70 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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70 participants in 9 patient groups

Part A: Cohort 1: TS-161 15 mg

Experimental group

Description:

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

Treatment:

Drug: TS-161 Placebo

Drug: TS-161

Part A: Cohort 2: TS-161 50 mg

Experimental group

Description:

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.

Treatment:

Drug: TS-161 Placebo

Drug: TS-161

Part A: Cohort 3: TS-161 100 mg

Experimental group

Description:

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.

Treatment:

Drug: TS-161 Placebo

Drug: TS-161

Part A: Cohort 4: TS-161 200 mg

Experimental group

Description:

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.

Treatment:

Drug: TS-161 Placebo

Drug: TS-161

Part A: Cohort 5: TS-161 400 mg

Experimental group

Description:

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.

Treatment:

Drug: TS-161 Placebo

Drug: TS-161

Part B: Cohort 6: TS-161 TBD

Experimental group

Description:

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

Treatment:

Drug: TS-161

Part C: Cohort 7: TS-161 TBD

Experimental group

Description:

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.

Treatment:

Drug: TS-161 Placebo

Drug: TS-161

Part C: Cohort 8: TS-161 TBD

Experimental group

Description:

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.

Treatment:

Drug: TS-161 Placebo

Drug: TS-161

Part C: Cohort 9: TS-161 TBD

Experimental group

Description:

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.

Treatment:

Drug: TS-161 Placebo

Drug: TS-161