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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: TS-134
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TS-134<br>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<br>* 5 mg, 10 mg, or 20 mg oral solution<br>|
| Placebo Comparator: Placebo<br>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<br>* Matched Placebo oral solution<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TS-134, CSF