Study of Oral Edaravone in Healthy Adult Males

Study Overview
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Brief Summary
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To evaluate the pharmacokinetics safety, and tolerability of single and multiple doses of edaravone solution and suspension in healthy adult males

Official Title
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Phase I Study of Oral Edaravone in Healthy Adult Males (Single- and Multiple-dose Study)

Conditions
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Healthy Adult Subjects

Intervention / Treatment
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* Drug: MT-1186
* Drug: MT-1186-matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Additional screening criteria check may apply for qualification: Healthy adult male volunteers Japanese or Caucasian Subjects aged between 20 and 45 years at the time of informed consent Subjects who have thoroughly understood the contents of the study and voluntarily provided written informed consent to participate in the study Exclusion Criteria: Additional screening criteria check may apply for qualification: Subjects with a current or previous history of cardiac, hepatic, renal, gastrointestinal, respiratory, psychiatric/nervous, hematopoietic, or endocrine diseases, and those whom the investigator (or subinvestigator) deems unsuitable for the study Body mass index (BMI) of <18.0 or >30.0, or body weight of <50 kg (BMI formula: body weight [kg]/height [m]2, rounded to one decimal place) Subjects who have undergone any surgery known to affect the gastrointestinal absorption of drugs Subjects who do not agree to use an effective method of contraception from initiation of study drug administration to 14 days after completion (discontinuation) of study drug administration Subjects who have previously received edaravone Subjects who have participated in another clinical study and received a study drug within 12 weeks before providing informed consent

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A single dose MT-1186 (Part 1, Cohort S1)<br>Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo. | Drug: MT-1186<br>* Solution or suspension<br>* Other names: Edaravone;Drug: MT-1186-matching placebo<br>* Solution or suspension<br>|
| Experimental: A single dose MT-1186 (Part 1, Cohort S2)<br>Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo. | Drug: MT-1186<br>* Solution or suspension<br>* Other names: Edaravone;Drug: MT-1186-matching placebo<br>* Solution or suspension<br>|
| Experimental: A single dose MT-1186 (Part 1, Cohort S3-1)<br>Healthy Japanese male subjects receive doses of MT-1186 or matching placebo. | Drug: MT-1186<br>* Solution or suspension<br>* Other names: Edaravone;Drug: MT-1186-matching placebo<br>* Solution or suspension<br>|
| Experimental: A single dose MT-1186 (Part 1, Cohort S3-2)<br>Healthy Japanese male subjects receive doses of MT-1186 or matching placebo. | Drug: MT-1186<br>* Solution or suspension<br>* Other names: Edaravone;Drug: MT-1186-matching placebo<br>* Solution or suspension<br>|
| Experimental: A single dose MT-1186 (Part 1, Cohort S4)<br>Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo. | Drug: MT-1186<br>* Solution or suspension<br>* Other names: Edaravone;Drug: MT-1186-matching placebo<br>* Solution or suspension<br>|
| Experimental: A single dose MT-1186 (Part 1, Cohort S5)<br>Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo. | Drug: MT-1186<br>* Solution or suspension<br>* Other names: Edaravone;Drug: MT-1186-matching placebo<br>* Solution or suspension<br>|
| Experimental: A single dose MT-1186 (Part 1, Cohort S6)<br>Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo. | Drug: MT-1186<br>* Solution or suspension<br>* Other names: Edaravone;Drug: MT-1186-matching placebo<br>* Solution or suspension<br>|
| Experimental: A single dose MT-1186 (Part 1, Cohort S7)<br>Healthy Caucasian male subjects receive a single dose of MT-1186 or matching placebo. | Drug: MT-1186<br>* Solution or suspension<br>* Other names: Edaravone;Drug: MT-1186-matching placebo<br>* Solution or suspension<br>|
| Experimental: Multiple doses MT-1186 (Part 2, Cohort M1)<br>Healthy Japanese male subjects receive multiple doses of MT-1186 or matching placebo. | Drug: MT-1186<br>* Solution or suspension<br>* Other names: Edaravone;Drug: MT-1186-matching placebo<br>* Solution or suspension<br>|
| Experimental: Multiple doses MT-1186 (Part 2, Cohort M2)<br>Healthy Japanese male subjects receive multiple doses of MT-1186 or matching placebo | Drug: MT-1186<br>* Solution or suspension<br>* Other names: Edaravone;Drug: MT-1186-matching placebo<br>* Solution or suspension<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse events and adverse drug reactions |  | Day 1 to 8 in part 1, day1 to 12 in part 2 | 
| Plasma concentrations | Plasma concentrations of unchanged edaravone, sulfate, and glucuronide for PK analysis | Day 1 to 3 in part 1, day 1 to 7 in part 2 | 
| PK parameters - Area under the concentration versus time curve (AUC) of unchanged edaravone, sulfate, and glucuronide | AUC from time zero to the last measured time point (AUC 0-last), AUC from time zero to 12 hours (AUC 0-12), from time zero to 24 hours (AUC 0-24), and AUC from time zero to infinity (AUC 0-inf) | Day 1 to 3 in part 1, day 1 to 7 in part 2 | 
| PK parameters - Maximum plasma concentration (Cmax) of unchanged edaravone, sulfate, and glucuronide |  | Day 1 to 3 in part 1, day 1 to 7 in part 2 | 
| PK parameters - Minimum plasma concentration (Ctrough) of unchanged edaravone, sulfate, and glucuronide |  | Day 1 to 7 in part 2 | 
| PK parameters - Time to reach maximum plasma concentration (tmax) of unchanged edaravone, sulfate, and glucuronide |  | Day 1 to 3 in part 1, day 1 to 7 in part 2 | 
| PK parameters - Terminal elimination half-life (t1/2) of unchanged edaravone, sulfate, and glucuronide |  | Day 1 to 3 in part 1, day 1 to 7 in part 2 | 
| PK parameters - Lambda-z of unchanged edaravone, sulfate, and glucuronide |  | Day 1 to 3 in part 1, day 1 to 7 in part 2 | 
| PK parameters - Mean residence time (MRT) of unchanged edaravone |  | Day 1 to 3 in part 1, day 1 to 7 in part 2 | 
| PK parameters - Apparent total clearance (CL/F) of unchanged edaravone |  | Day 1 to 3 in part 1, day 1 to 7 in part 2 | 
| PK parameters - Apparent distribution volume at elimination phase (Vz/F) of unchanged edaravone |  | Day 1 to 3 in part 1, day 1 to 7 in part 2 | 
| PK parameters - Apparent distribution volume at steady state (Vss/F) of unchanged edaravone |  | Day 1 to 3 in part 1, day 1 to 7 in part 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate |  | Day 1 to 3 in cohort 4, 5 and 6 in part 1 | 
| PR interval |  | Day 1 to 3 in cohort 4, 5 and 6 in part 1 | 
| QT interval |  | Day 1 to 3 in cohort 4, 5 and 6 in part 1 | 
| QTcF |  | Day 1 to 3 in cohort 4, 5 and 6 in part 1 | 
| QRS interval |  | Day 1 to 3 in cohort 4, 5 and 6 in part 1 |