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

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ClinicalTrials.gov Identifier: NCT03919409
Recruitment Status : Recruiting
First Posted : April 18, 2019
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
Taisho Pharmaceutical R&D Inc.

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

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.
Drug: TS-161
TS-161 capsules

Drug: TS-161 Placebo
TS-161 matching placebo capsules

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




Primary Outcome Measures :
  1. Incidence and severity of Adverse Events [ Time Frame: Parts A and B: Day 1 to Day 8; Part C: Day 1 to Day 17 ]
  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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 :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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 ]


Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03919409


Contacts
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Contact: Taisho Pharmaceutical R&D Inc. 888-602-0203 ClinicalTrials@taisho-rd.com

Locations
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United States, California
PAREXEL - Early Phase Clinical Unit-Los Angeles Recruiting
Glendale, California, United States, 91206
Sponsors and Collaborators
Taisho Pharmaceutical R&D Inc.
Investigators
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Study Director: Taisho Director Taisho Pharmaceutical R&D Inc.

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Responsible Party: Taisho Pharmaceutical R&D Inc.
ClinicalTrials.gov Identifier: NCT03919409     History of Changes
Other Study ID Numbers: TS161-US101
First Posted: April 18, 2019    Key Record Dates
Last Update Posted: June 11, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Taisho Pharmaceutical R&D Inc.:
TS-161
CSF
first-in-human