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

Sponsor

Taisho Pharmaceutical R&D Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03742791

Collaborator

(none)

Enrollment

Location

Arms

5.5

Actual Duration (Months)

10.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: TS-134 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

Double-blind (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Titration Study to Evaluate the Safety, Tolerability and Pharmacokinetics of TS-134 Administered Orally to Healthy Male and Female Subjects

Actual Study Start Date :

Jun 28, 2016

Actual Primary Completion Date :

Dec 12, 2016

Actual Study Completion Date :

Dec 12, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TS-134 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 5 mg to 80 mg oral solution
Placebo Comparator: Placebo 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 Matched Placebo oral solution

Arm

Intervention/Treatment

Experimental: TS-134

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

5 mg to 80 mg oral solution

Placebo Comparator: Placebo

Drug: Placebo

Matched Placebo oral solution

Outcome Measures

Primary Outcome Measures

Incidence and Severity of Adverse Events [Day 1 to Day 21]
TS-134 Plasma Pharmacokinetic Profile - Cmax [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]
Maximum plasma concentration
TS-134 Plasma Pharmacokinetic Profile - AUC(0-tau) [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]
Area under the plasma concentration vs time curve over a dosing interval
TS-134 Plasma Pharmacokinetic Profile - tmax [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]
Time to maximum plasma concentration
TS-134 Plasma Pharmacokinetic Profile - t1/2 [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]
Apparent terminal elimination half-life
TS-134 Plasma Pharmacokinetic Profile - CL/F [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]
Apparent clearance following oral administration
TS-134 Plasma Pharmacokinetic Profile - Vd/F [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]
Apparent volumes of distribution following oral administration

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Taisho Pharmaceutical R&D Inc.

ClinicalTrials.gov Identifier:

NCT03742791

Other Study ID Numbers:

TS134-US102

First Posted:

Nov 15, 2018

Last Update Posted:

Nov 15, 2018

Last Verified:

Nov 1, 2018

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Taisho Pharmaceutical R&D Inc.

TS-134, multiple dose, titration

Study Results

No Results Posted as of Nov 15, 2018