Healthy Volunteers
Conditions
Keywords
TS-161, CSF, first-in-human
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.
Interventions
DRUGTS-161
TS-161 capsules
DRUGTS-161 Placebo
TS-161 matching placebo capsules
Sponsors
Taisho Pharmaceutical R&D Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| TS-161 CSF Pharmacokinetic Profile - Cmax | Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose | Maximum CSF concentration |
| 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 |
| 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 |
| 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 |
Countries
United States
Outcome results
None listed