Clinical Study of TS-143 in Healthy Adult Male Subjects (Multiple-Dose Administration)

Study Overview
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Brief Summary
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To investigate the safety, pharmacokinetics and pharmacodynamics of TS-143 when administered 3 times a day for 10 days to healthy Japanese adult males using placebo-controlled, double-blind, dose escalation study design.

Official Title
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Phase I Clinical Study of TS-143 in Healthy Adult Male Subjects (Multiple-Dose Administration)

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: TS-143
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a BMI of 18.5 to less than 25.0 at the time of the screening tests Subjects judged by the principal investigator or a subinvestigator to be appropriate for participation in the study based on the results of the screening tests and the tests conducted before the investigational drug treatment on Day 1 Subjects capable of receiving an explanation of this study before participation, understanding the details, and providing written informed consent themselves Exclusion Criteria: Subjects meeting any of the following criteria in the results of screening tests, tests conducted on the day before the first investigational treatment (Day -1), and tests conducted before the investigational drug treatment on the morning of Day 1: Red blood cell count: ≥535 × 10^4 /μL Hemoglobin: ≥16.2 g/dL Hematocrit: ≥47.5% Reticulocyte rate: Outside of the reference value range Subjects meeting any of the following criteria in the screening tests: Serum EPO concentration: Outside of the reference value range Ferritin: ≤30 ng/mL or >upper limit of the reference value Subjects meeting any of the following criteria in the vital signs in the screening tests and the tests conducted before the investigational drug treatment on the morning of Day 1: Blood pressure: Systolic blood pressure ≥140 mmHg, or diastolic blood pressure ≥90 mmHg Pulse rate: <40 bpm, or ≥100 bpm Body temperature: ≥37.5°C

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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Male

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: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Step1:4㎎ TID<br>TS-143 12mg total dose/day or Placebo | Drug: TS-143<br>* Subjects should take 4 capsules once and 3 times per day in step 1. Subjects should take 2 capsules once and 3 times per day in step 2.<br>Drug: Placebo<br>* Subjects should take 4 capsules once and 3 times per day in step 1. Subjects should take 2 capsules once and 3 times per day in step 2.<br>|
| Other: Step2:11㎎ TID<br>TS-143 33mg total dose/day or Placebo | Drug: TS-143<br>* Subjects should take 4 capsules once and 3 times per day in step 1. Subjects should take 2 capsules once and 3 times per day in step 2.<br>Drug: Placebo<br>* Subjects should take 4 capsules once and 3 times per day in step 1. Subjects should take 2 capsules once and 3 times per day in step 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of subjects with adverse events | To evaluate the safety of TS-143 given single administration in healthy volunteers by incidence of subjects with adverse events which include abnormal electrocardiograms, vital signs, and clinical laboratory parameters. | 18 days | 
| Plasma concentrations of unchanged form (ng/mL) |  | 13 days | 
| Urinary excretions of unchanged form (ng/mL) |  | 12 days | 
| Serum EPO concentration |  | 13 days | 
| Reticulocyte count |  | 13 days | 
| Plasma vascular endothelial growth factor (VEGF) concentration |  | 13 days | 
| Serum iron (μg／dL) |  | 13 days | 
| Total iron binding capacity（μg／dL） |  | 13 days |