Clinical trial NCT03919409: First-in-Human Study With Single and Multiple Doses of TS-161 in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: TS-161
CSF
first-in-human
Lead sponsor: Taisho Pharmaceutical R&D Inc.
Sponsor class: INDUSTRY
First posted: 2019-04-18
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of Adverse Events
timeFrame: Parts A and B: Day 1 to Day 8; Part C: Day 1 to Day 17
measure: TS-161 Plasma Pharmacokinetic Profile - Cmax
timeFrame: 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
measure: TS-161 Plasma Pharmacokinetic Profile - Tmax
timeFrame: 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
measure: TS-161 Plasma Pharmacokinetic Profile - AUC(0-last)
timeFrame: Parts A and B: Day 1 predose and at multiple time points (up to 48 hours) postdose
measure: TS-161 Plasma Pharmacokinetic Profile - AUC(0-tau)
timeFrame: 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
measure: TS-161 Plasma Pharmacokinetic Profile - T1/2
timeFrame: 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
measure: TS-161 Plasma Pharmacokinetic Profile - CL/F
timeFrame: 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
measure: TS-161 Plasma Pharmacokinetic Profile - Vd,z/F
timeFrame: 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
measure: TS-161 Urine Pharmacokinetic Profile - Ae
timeFrame: 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
measure: TS-161 Urine Pharmacokinetic Profile - Fe%
timeFrame: 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
measure: TS-161 Urine Pharmacokinetic Profile - CLr
timeFrame: 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 outcomes:
measure: TS-161 CSF Pharmacokinetic Profile - Cmax
timeFrame: Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose
measure: TS-161 CSF Pharmacokinetic Profile - Tmax
timeFrame: Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose
measure: TS-161 CSF Pharmacokinetic Profile - AUC(0-last)
timeFrame: Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose
measure: TS-161 CSF Pharmacokinetic Profile - T1/2
timeFrame: Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose
measure: Changes from baseline in relative and absolute powers of the delta, theta, alpha, beta and gamma bands using quantitative electroencephalogram (qEEG) compared to placebo
timeFrame: Part A: predose and at multiple time points (up to 8 hours) postdose
Other outcomes:
Locations:
city: Glendale
country: United States
facility: PAREXEL - Early Phase Clinical Unit-Los Angeles
state: California
Study officials:
affiliation: Taisho Pharmaceutical R&D Inc.
name: Taisho Director
role: STUDY_DIRECTOR
References: