Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Males (Drug Interaction Study and Preliminary Regimen-Finding Study)

Study Overview
=================
Brief Summary
-----------------
Cohort 1: To evaluate the drug interactions, safety, and tolerability of oral edaravone when coadministered with rosuvastatin, sildenafil or furosemide in healthy adult males Cohort 2: To evaluate the pharmacokinetics, safety, and tolerability of oral edaravone in healthy Japanese and Caucasian adult males

Official Title
-----------------
Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Males (Drug Interaction Study and Preliminary Regimen-Finding Study)

Conditions
-----------------
Healthy Adult Subjects

Intervention / Treatment
-----------------
* Drug: MT-1186
* Drug: Rosuvastatin
* Drug: Sildenafil
* Drug: Furosemide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adult male volunteers Cohort 1: Japanese, Cohort 2: 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 Use of any drug(s) other than the study drug or as-needed use of acetylsalicylic acid within 7 days before the initiation of study drug or victim drug administration Use of any alcohol, xanthine, or caffeine-containing product(s) within 24 hours before screening and Day -1 visiting Use of any supplement(s) within 7 days before the initiation of study drug or victim drug administration Use of grapefruit, grapefruit juice, or any processed food(s) containing these substances during the following periods (Cohort 1: within 7 days before the initiation of victim drug administration, Cohort 2: within 24 hours before each Day -1 visiting) Use of any tobacco or nicotine-containing product(s) (Cohort 1: within 12 weeks before the initiation of victim drug administration during the following periods, Cohort 2: within 24 hours before each Day -1 visiting) Use of any health food(s) containing St John's Wort (Hypericum perforatum) within 2 weeks before the initiation of victim drug administration (only in Cohort 1)

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

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

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

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Cohort 1 is open-label, non-randomized, sequential, and add-on study. Cohort 2 is single-dose, open-label, randomized, and cross-over study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rosuvastatin, Sildenafil, and MT-1186<br>Group 1 of Cohort 1: A single-sequence study in which healthy male subjects receive a single dose of rosuvastatin on Day 1 followed by a single dose of sildenafil on Day 4. MT-1186 will be administered from Day 6 to 13 with co-administration of rosuvastatin and sildenafil on Day 9 and 12, respectively. | Drug: MT-1186<br>* Suspension<br>* Other names: Edaravone;Drug: Rosuvastatin<br>* Tablets<br>* Other names: Crestor;Drug: Sildenafil<br>* Tablets<br>* Other names: Viagra;|
| Experimental: Furosemide and MT-1186<br>Group 2 of Cohort 1: A single-sequence study in which healthy male subjects receive a single dose of furosemide on Day 1. MT-1186 will be administered from Day 3 to 7 with co-administration of furosemide on Day 6. | Drug: MT-1186<br>* Suspension<br>* Other names: Edaravone;Drug: Furosemide<br>* Tablets<br>* Other names: Lasix;|
| Experimental: MT-1186<br>Cohort 2: A three-way crossover study in which Japanese healthy male subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 4, and 7 according to their treatment sequence with 3-day wash out between doses. Caucasian healthy male subjects receive a single dose of MT-1186 at the same period with Japanese subjects under the corresponding condition on Day 1, 4, or 7 according to their treatment schedule. | Drug: MT-1186<br>* Suspension<br>* Other names: Edaravone;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters - Area under the concentration versus time curve from time zero to infinity (AUC 0-inf) of rosuvastatin, sildenafil, furosemide, and unchanged edaravone, sulfate, glucuronide |  | Day 1 to 14 in group 1 of cohort 1, Day 1 to 8 in group 2 of cohort 1, Day 1 to 9 in cohort 2 | 
| PK parameters - Maximum plasma concentration (Cmax) of rosuvastatin, sildenafil, furosemide, and unchanged edaravone, sulfate, glucuronide |  | Day 1 to 14 in group 1 of cohort 1, Day 1 to 8 in group 2 of cohort 1, Day 1 to 9 in cohort 2 | 
| PK parameters - Time to reach maximum plasma concentration (tmax) of rosuvastatin, sildenafil, furosemide, and unchanged edaravone, sulfate, glucuronide |  | Day 1 to 14 in group 1 of cohort 1, Day 1 to 8 in group 2 of cohort 1, Day 1 to 9 in cohort 2 | 
| PK parameters - Terminal elimination half-life (t1/2) of rosuvastatin, sildenafil, furosemide, and unchanged edaravone, sulfate, glucuronide |  | Day 1 to 14 in group 1 of cohort 1, Day 1 to 8 in group 2 of cohort 1, Day 1 to 9 in cohort 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse events and adverse drug reactions |  | Day 1 to 20 in group 1 of cohort 1, Day 1 to 14 in group 2 of cohort 1, Day 1 to 14 of cohort 2 |