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

• Sponsor: Taisho Pharmaceutical R&D Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03746067
• Collaborator: (none)
• Enrollment: 33
• Location: 1
• Arms: 2
• Actual Duration (Months): 4.8
• Patients Per Site Per Month: 6.9

Study Details

Study Description

Brief Summary

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.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double-blind
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Aug 21, 2015
• Actual Primary Completion Date: Jan 13, 2016
• Actual Study Completion Date: Jan 13, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Incidence and severity of Adverse Events [Day 1 to Day 7]

2. TS-134 Plasma Pharmacokinetic Profile - Cmax [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]

   Maximum plasma concentration

3. TS-134 Plasma Pharmacokinetic Profile - AUC(0-last) [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]

   Area under the concentration vs. time curve from time zero to last measurable concentration

4. TS-134 Plasma Pharmacokinetic Profile - tmax [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]

   Time to maximum plasma concentration

5. TS-134 Plasma Pharmacokinetic Profile - t1/2 [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]

   Apparent terminal elimination half-life

6. TS-134 Plasma Pharmacokinetic Profile - CL/F [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]

   Apparent clearance following oral administration

7. TS-134 Plasma Pharmacokinetic Profile - Vd/F [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]

   Apparent volumes of distribution following oral administration

Secondary Outcome Measures

1. TS-134 Cerebral Spinal Fluid (CSF) Pharmacokinetic Profile - Cmax [Day 1: predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose]

   Maximum CSF concentration

2. TS-134 CSF Pharmacokinetic Profile - AUC(0-last) [Day 1: predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose]

   Area under the CSF concentration vs. time curve from time zero to last measurable concentration

3. TS-134 CSF Pharmacokinetic Profile - tmax [Day 1: predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose]

   Time to maximum CSF concentration

4. TS-134 CSF Pharmacokinetic Profile - t1/2 [Day 1: predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose]

   Apparent terminal elimination half-life (CSF)

5. TS-134 CSF Pharmacokinetic Profile - CL/F [Day 1: predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose]

   Apparent clearance (CSF) following oral administration

6. TS-134 CSF Pharmacokinetic Profile - Vd/F [Day 1: predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose]

   Apparent volumes of distribution (CSF) 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: NCT03746067
• Other Study ID Numbers: TS134-US101
• First Posted: Nov 19, 2018
• Last Update Posted: Nov 19, 2018
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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-134, CSF

Study Results

No Results Posted as of Nov 19, 2018