Safety, Tolerability and Pharmacokinetics of Single Doses of TS-134 in Healthy Volunteers

A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Effects of Food on the Absorption of TS-134 Administered Orally to Healthy Male and Female Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: TS-134

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • PAREXEL - Early Phase Clinical Unit-Los Angeles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TS-134; Healthy adult subjects will be prospectively assigned to 1 of 4 cohorts. Within each cohort, 8 subjects will be randomized in a 3:1 ratio (6 active + 2 placebo) per cohort to receive TS-134 or placebo as a single oral dose solution. All cohorts will be dosed in a fasted state except for the 2nd and 4th (food effect) cohorts, which will be dosed first in a fasted state, and then in a fed state, in a single crossover design conducted with a washout between two periods. In the 3rd (CSF) cohort, 8 subjects will receive one dose level of TS-134 as a single-blind dosing assignment; there will be no placebo dosing.	Drug: TS-134; 5 mg, 10 mg, or 20 mg oral solution
Placebo Comparator: Placebo; Healthy adult subjects will be prospectively assigned to 1 of 4 cohorts. Within each cohort, 8 subjects will be randomized in a 3:1 ratio (6 active + 2 placebo) per cohort to receive TS-134 or placebo as a single oral dose solution. All cohorts will be dosed in a fasted state except for the 2nd and 4th (food effect) cohorts, which will be dosed first in a fasted state, and then in a fed state, in a single crossover design conducted with a washout between two periods. In the 3rd (CSF) cohort, the 8 subjects will receive one dose level of TS-134 as a single-blind dosing assignment; there will be no placebo dosing.	Drug: Placebo; Matched Placebo oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Adverse Events		Day 1 to Day 7
TS-134 Plasma Pharmacokinetic Profile - Cmax	Maximum plasma concentration	Day 1: predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose
TS-134 Plasma Pharmacokinetic Profile - AUC(0-last)	Area under the concentration vs. time curve from time zero to last measurable concentration	Day 1: predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose
TS-134 Plasma Pharmacokinetic Profile - tmax	Time to maximum plasma concentration	Day 1: predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose
TS-134 Plasma Pharmacokinetic Profile - t1/2	Apparent terminal elimination half-life	Day 1: predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose
TS-134 Plasma Pharmacokinetic Profile - CL/F	Apparent clearance following oral administration	Day 1: predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose
TS-134 Plasma Pharmacokinetic Profile - Vd/F	Apparent volumes of distribution following oral administration	Day 1: predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TS-134 Cerebral Spinal Fluid (CSF) Pharmacokinetic Profile - Cmax	Maximum CSF concentration	Day 1: predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose
TS-134 CSF Pharmacokinetic Profile - AUC(0-last)	Area under the CSF concentration vs. time curve from time zero to last measurable concentration	Day 1: predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose
TS-134 CSF Pharmacokinetic Profile - tmax	Time to maximum CSF concentration	Day 1: predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose
TS-134 CSF Pharmacokinetic Profile - t1/2	Apparent terminal elimination half-life (CSF)	Day 1: predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose
TS-134 CSF Pharmacokinetic Profile - CL/F	Apparent clearance (CSF) following oral administration	Day 1: predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose
TS-134 CSF Pharmacokinetic Profile - Vd/F	Apparent volumes of distribution (CSF) following oral administration	Day 1: predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose

Collaborators and Investigators

• Sponsor: Taisho Pharmaceutical R&D Inc.
• Investigators: Study Director: Taisho Director, Taisho Pharmaceutical R&D Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2015
• Primary Completion (Actual): January 13, 2016
• Study Completion (Actual): January 13, 2016

Study Registration Dates

• First Submitted: October 18, 2018
• First Submitted That Met QC Criteria: November 14, 2018
• First Posted (Actual): November 19, 2018

Study Record Updates

• Last Update Posted (Actual): November 19, 2018
• Last Update Submitted That Met QC Criteria: November 14, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: TS-134, CSF
• Other Study ID Numbers: TS134-US101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No