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出境医 / 临床实验 / First-in-Human Study With Single and Multiple Doses of TS-161 in Healthy Participants
First-in-Human Study With Single and Multiple Doses of TS-161 in Healthy Participants
Study Description
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Healthy Volunteers | Drug: TS-161 Drug: TS-161 Placebo | Phase 1 |
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 70 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | June 3, 2019 |
| Actual Primary Completion Date : | February 11, 2020 |
| Actual Study Completion Date : | February 11, 2020 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Part A: Cohort 1: TS-161 15 mg
Single dose of TS-161 15 mg or placebo in a fasted condition.
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Drug: TS-161
TS-161 capsules
Drug: TS-161 Placebo TS-161 matching placebo capsules
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Experimental: Part A: Cohort 2: TS-161 50 mg
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.
|
Drug: TS-161
TS-161 capsules
Drug: TS-161 Placebo TS-161 matching placebo capsules
|
|
Experimental: Part A: Cohort 3: TS-161 100 mg
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.
|
Drug: TS-161
TS-161 capsules
Drug: TS-161 Placebo TS-161 matching placebo capsules
|
|
Experimental: Part A: Cohort 4: TS-161 200 mg
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.
|
Drug: TS-161
TS-161 capsules
Drug: TS-161 Placebo TS-161 matching placebo capsules
|
|
Experimental: Part A: Cohort 5: TS-161 400 mg
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.
|
Drug: TS-161
TS-161 capsules
Drug: TS-161 Placebo TS-161 matching placebo capsules
|
|
Experimental: Part B: Cohort 6: TS-161 TBD
Single dose of TS-161 in a fasted condition. The dose level will be determined based on the results from the preceding cohorts.
|
Drug: TS-161
TS-161 capsules
|
|
Experimental: Part C: Cohort 7: TS-161 TBD
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.
|
Drug: TS-161
TS-161 capsules
Drug: TS-161 Placebo TS-161 matching placebo capsules
|
|
Experimental: Part C: Cohort 8: TS-161 TBD
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.
|
Drug: TS-161
TS-161 capsules
Drug: TS-161 Placebo TS-161 matching placebo capsules
|
|
Experimental: Part C: Cohort 9: TS-161 TBD
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.
|
Drug: TS-161
TS-161 capsules
Drug: TS-161 Placebo TS-161 matching placebo capsules
|
Outcome Measures
Primary Outcome Measures :
- Incidence and severity of Adverse Events [ Time Frame: Parts A and B: Day 1 to Day 8; Part C: Day 1 to Day 17 ]
- TS-161 Plasma Pharmacokinetic Profile - Cmax [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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% [ Time Frame: 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 [ Time Frame: 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 Outcome Measures :
- TS-161 CSF Pharmacokinetic Profile - Cmax [ Time Frame: Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose ]Maximum CSF concentration
- TS-161 CSF Pharmacokinetic Profile - Tmax [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Part B: Day 1 predose and at multiple time points (up to 24 hours) postdose ]Apparent terminal elimination half-life
- Changes from baseline in relative and absolute powers of the delta, theta, alpha, beta and gamma bands using quantitative electroencephalogram (qEEG) compared to placebo [ Time Frame: Part A: predose and at multiple time points (up to 8 hours) postdose ]
Eligibility Criteria
| Ages Eligible for Study: | 18 Years to 55 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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
Contacts and Locations
Locations
| United States, California | |
| PAREXEL - Early Phase Clinical Unit-Los Angeles | |
| Glendale, California, United States, 91206 | |
Sponsors and Collaborators
Taisho Pharmaceutical R&D Inc.
Investigators
| Study Director: | Taisho Director | Taisho Pharmaceutical R&D Inc. |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | April 15, 2019 | ||||
| First Posted Date ICMJE | April 18, 2019 | ||||
| Last Update Posted Date | February 28, 2020 | ||||
| Actual Study Start Date ICMJE | June 3, 2019 | ||||
| Actual Primary Completion Date | February 11, 2020 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
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| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE | Same as current | ||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | First-in-Human Study With Single and Multiple Doses of TS-161 in Healthy Participants | ||||
| Official Title ICMJE | 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 | ||||
| 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. |
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| Detailed Description | Not Provided | ||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Phase 1 | ||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment |
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| Condition ICMJE | Healthy Volunteers | ||||
| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Completed | ||||
| Actual Enrollment ICMJE |
70 | ||||
| Original Estimated Enrollment ICMJE | Same as current | ||||
| Actual Study Completion Date ICMJE | February 11, 2020 | ||||
| Actual Primary Completion Date | February 11, 2020 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
Exclusion Criteria for Part B only:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years to 55 Years (Adult) | ||||
| Accepts Healthy Volunteers ICMJE | Yes | ||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
| Listed Location Countries ICMJE | United States | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT03919409 | ||||
| Other Study ID Numbers ICMJE | TS161-US101 | ||||
| Has Data Monitoring Committee | Not Provided | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Taisho Pharmaceutical R&D Inc. | ||||
| Study Sponsor ICMJE | Taisho Pharmaceutical R&D Inc. | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE |
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| PRS Account | Taisho Pharmaceutical R&D Inc. | ||||
| Verification Date | February 2020 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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