Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Subjects (Food Effect Study)

Study Overview
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Brief Summary
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To evaluate the effect of food on the pharmacokinetics of oral edaravone in healthy adult subjects. In this study, we determined 5 different dietary conditions including 4 diffrerent meal contents and fasting condition.

Official Title
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Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Subjects (Food Effect Study)

Conditions
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Healthy Adult Subjects

Intervention / Treatment
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* Drug: MT-1186


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who meet all of the following criteria and who have the capability of giving informed consent will be included in the study. Healthy adult male or female volunteers Japanese 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: Subjects who met any of the following exclusion criteria between screening and investigational product administration were excluded from the study: 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 History of drug or food allergies History of alcohol or drug abuse or dependence Body mass index (BMI) of < 18.0 or > 30.0, or a body weight of < 50 kg [BMI formula: body weight (kg)/height (m)2, rounded to one decimal place] Positive test for any of the following at screening: hepatitis B surface (HBs) antigen, serological test for syphilis, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen/antibody Any clinically significant 12-lead ECG abnormality or corrected QT interval (QTc) using Fridericia's formula (QTcF) interval ≥ 450 msec Blood donation or sampling with a total volume of ≥ 400 mL within 12 weeks, ≥ 200 mL within 4 weeks, or ≥ 800 mL within one year before providing informed consent Blood component donation or blood sampling within 2 weeks before providing informed consent Subjects who have undergone any surgery known to affect the gastrointestinal absorption of drugs (except for appendectomy and herniotomy) Female subjects who do not agree to use an effective method of contraception from screening or 2 weeks before the start of investigational product administration, whichever comes earlier, to 14 days after the completion (or discontinuation) of investigational product administration. Male subjects who do not agree to use an effective method of contraception from the start of investigational product administration to 14 days after the completion (or discontinuation) of investigational product administration Subjects who have previously received edaravone Subjects who have participated in another clinical study and received an investigational product within 12 weeks before providing informed consent Subjects who have used any drugs other than the single use of acetylsalicylic acid within 7 days before the initiation of investigational product administration Use of any nutritional supplement(s) within 7 days before the initiation of investigational product administration Use of alcohol or any products containing xanthin or caffeine within 24 hours before screening and visit on Day -1 Use of grapefruit, grapefruit juice, or any processed food(s) containing these substances within 24 hours before screening and visit on Day -1 Use of any tobacco or nicotine-containing product(s) within 24 hours before screening and visit on Day -1 Female subjects who have a positive pregnancy test at screening and on Day -1, are pregnant or breast feeding, or plan to get pregnant during the study Subjects judged by the investigator (or subinvestigator) to be unsuitable for the study for any other reason

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>A single oral dose of MT-1186 with fasted condition in period 1, meal 1 condition in period 2, meal 2 condition in period 3, meal 3 condition in period 4, and meal 4 condition in period 5. | Drug: MT-1186<br>* A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence.<br>* Other names: Edaravone;|
| Experimental: Group B<br>A single oral dose of MT-1186 with meal 1 condition in period 1, meal 2 condition in period 2, meal 3 condition in period 3, fasted condition in period 4, and meal 4 condition in periond 5. | Drug: MT-1186<br>* A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence.<br>* Other names: Edaravone;|
| Experimental: Group C<br>A single oral dose of MT-1186 with meal 2 condition in period 1, meal 3 condition in period 2, fasted condition in period 3, meal 1 condition in period 4, and meal 4 condition in period 5. | Drug: MT-1186<br>* A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence.<br>* Other names: Edaravone;|
| Experimental: Group D<br>A single oral dose of MT-1186 with meal 3 condition in period 1, fasted condition in period 2, meal 1 condition in period 3, meal 2 in period 4, and meal 4 condition in period 5. | Drug: MT-1186<br>* A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence.<br>* Other names: Edaravone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug concentration of edaravone, sulfate conjugate, and glucuronide conjugate in plasma and urine |  | Day 1 to 9, Day 24 to 26 | 
| Area under the concentration versus time curve (AUC) of edaravone, sulfate conjugate, and glucuronide conjugate |  | Day 1 to 9, Day 24 to 26 | 
| Maximum plasma concentration (Cmax) of edaravone, sulfate conjugate, and glucuronide conjugate |  | Day 1 to 9, Day 24 to 26 | 
| Time to reach maximum plasma concentration (tmax) of edaravone, sulfate conjugate, and glucuronide conjugate |  | Day 1 to 9, Day 24 to 26 | 
| Terminal elimination half-life (t1/2) of edaravone, sulfate conjugate, and glucuronide conjugate |  | Day 1 to 9, Day 24 to 26 | 
| Apparent terminal elimination rate constant (Kel) of edaravone, sulfate conjugate, and glucuronide conjugate |  | Day 1 to 9, Day 24 to 26 | 
| Mean residence time (MRT) of edaravone |  | Day 1 to 9, Day 24 to 26 | 
| Apparent total clearance (CL/F) of edaravone |  | Day 1 to 9, Day 24 to 26 | 
| Apparent distribution volume at elimination phase (Vz/F) of edaravone |  | Day 1 to 9, Day 24 to 26 | 
| Apparent distribution volume at steady state (Vss/F) of edaravone |  | Day 1 to 9, Day 24 to 26 | 
| Cumulative urinary excretion amount (Ae) of edaravone, sulfate conjugate, and glucuronide conjugate |  | Day 1 to 9, Day 24 to 26 | 
| Urinary excretion ratio (Ae%) of edaravone, sulfate conjugate, and glucuronide conjugate |  | Day 1 to 9, Day 24 to 26 | 
| Renal clearance (CLr) of edaravone |  | Day 1 to 9, Day 24 to 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse events and adverse drug reactions |  | The provision of informed consent to Day 31 |