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.

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