Safety, Tolerability and Pharmacokinetics of 14-day Multiple Dose Titrations of TS-134 in Healthy Volunteers

NCT03742791 | Completed Phase 1 FDA Drug

• 1 other identifier: TS134-US102
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 study involving multiple dose titrations of TS-134 in healthy male and female subjects. The safety, tolerability and pharmacokinetics of multiple dose titrations of TS-134 will be evaluated.

Conditions

Healthy Volunteers

Keywords

TS-134, multiple dose, titration

Outcome Measures

Primary Outcomes (7)

• Incidence and Severity of Adverse Events

  Day 1 to Day 21

• TS-134 Plasma Pharmacokinetic Profile - Cmax

  Maximum plasma concentration

  Cohort 1: Day 1, Day 7, Day 8, Day 14, Cohort 2-3: Day 7, Day 14, Cohort 4-5: Day 9, Day 14, Cohort 6: Day 5, Day 14: predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12h post-dose; Day 1 to Day 14 except above days: predose

• TS-134 Plasma Pharmacokinetic Profile - AUC(0-tau)

  Area under the plasma concentration vs time curve over a dosing interval

  Cohort 1: Day 1, Day 7, Day 8, Day 14, Cohort 2-3: Day 7, Day 14, Cohort 4-5: Day 9, Day 14, Cohort 6: Day 5, Day 14: predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12h post-dose; Day 1 to Day 14 except above days: predose

• TS-134 Plasma Pharmacokinetic Profile - tmax

  Time to maximum plasma concentration

  Cohort 1: Day 1, Day 7, Day 8, Day 14, Cohort 2-3: Day 7, Day 14, Cohort 4-5: Day 9, Day 14, Cohort 6: Day 5, Day 14: predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12h post-dose; Day 1 to Day 14 except above days: predose

• TS-134 Plasma Pharmacokinetic Profile - t1/2

  Apparent terminal elimination half-life

  Cohort 1: Day 1, Day 7, Day 8, Day 14, Cohort 2-3: Day 7, Day 14, Cohort 4-5: Day 9, Day 14, Cohort 6: Day 5, Day 14: predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12h post-dose; Day 1 to Day 14 except above days: predose

• TS-134 Plasma Pharmacokinetic Profile - CL/F

  Apparent clearance following oral administration

  Cohort 1: Day 1, Day 7, Day 8, Day 14, Cohort 2-3: Day 7, Day 14, Cohort 4-5: Day 9, Day 14, Cohort 6: Day 5, Day 14: predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12h post-dose; Day 1 to Day 14 except above days: predose

• TS-134 Plasma Pharmacokinetic Profile - Vd/F

  Apparent volumes of distribution following oral administration

  Cohort 1: Day 1, Day 7, Day 8, Day 14, Cohort 2-3: Day 7, Day 14, Cohort 4-5: Day 9, Day 14, Cohort 6: Day 5, Day 14: predose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12h post-dose; Day 1 to Day 14 except above days: predose

Study Arms (2)

TS-134

EXPERIMENTAL

Healthy adult subjects will be prospectively assigned to 1 of 6 cohorts. Within each cohort, 10 subjects per cohort will be randomized in a 4:1 ratio (8 active + 2 placebo) to receive daily doses of TS-134 or placebo for 14 days in a fed state, with ascending titrated dose levels ranging from 5 mg to 80 mg, depending on the assigned cohort. The maximum daily dose shall not exceed 80 mg.

Drug: TS-134

Placebo

PLACEBO COMPARATOR

Healthy adult subjects will be prospectively assigned to 1 of 6 cohorts. Within each cohort, 10 subjects per cohort will be randomized in a 4:1 ratio (8 active + 2 placebo) to receive daily doses of TS-134 or placebo for 14 days in a fed state, with ascending titrated dose levels ranging from 5 mg to 80 mg, depending on the assigned cohort. The maximum daily dose shall not exceed 80 mg.

Drug: Placebo

Interventions

TS-134 DRUG

5 mg to 80 mg oral solution

TS-134

Placebo DRUG

Matched Placebo oral solution

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult male and female participants between 18 and 55 years of age
• Body weight greater than or equal to 45 kg
• Body Mass Index (BMI) greater than or equal to 18 and less than or equal to 30 kg/m\^2

You may not qualify if:

• Female participants who are pregnant, intend to become pregnant, or are breastfeeding
• Clinically significant abnormal physical examination, 12-lead electrocardiogram (ECG) OR cardiac telemetry prior to dosing.
• Significant history or presence of hepatic, renal, cardiovascular, pulmonary, gastrointestinal, hematological, locomotor, immunologic, ophthalmologic, metabolic or oncological disease.
• History or presence of psychiatric or neurologic disease or condition
• History of alcohol or drug abuse
• Any participant who currently uses or has used tobacco or tobacco-containing products for at least one month prior to screening
• Participated in strenuous exercise within 48 hours prior to study start (initial dosing) and/or are unwilling to avoid strenuous exercise at any time throughout the study.

Sponsors & Collaborators

• Taisho Pharmaceutical R&D Inc.: lead

Study Sites (1)

PAREXEL - Early Phase Clinical Unit-Los Angeles

Glendale, California, 91206, United States

Location

Study Officials

• Taisho Director

  Taisho Pharmaceutical R&D Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind (Participant, Investigator)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: November 15, 2018
• Study Start: June 28, 2016
• Primary Completion: December 12, 2016
• Study Completion: December 12, 2016
• Last Updated: November 15, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)