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

Study Overview
=================
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.

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

Conditions
-----------------
Healthy Volunteers

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


Participation Criteria
=================
Eligibility Criteria
-----------------
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
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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 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<br>* 5 mg to 80 mg oral solution<br>|
| Placebo Comparator: Placebo<br>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<br>* Matched Placebo oral solution<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TS-134, multiple dose, titration