Clinical trial NCT04481789: Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Males (Drug Interaction Study and Preliminary Regimen-Finding Study)
Official title: Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Males (Drug Interaction Study and Preliminary Regimen-Finding Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adult Subjects
Lead sponsor: Mitsubishi Tanabe Pharma Corporation
Sponsor class: INDUSTRY
First posted: 2020-07-22
Enrollment: 84
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: OTHER

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


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)

Primary outcomes:
measure: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Rosuvastatin, Sildenafil and Furosemide.
timeFrame: Before rosuvastatin dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before sildenafil dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before furosemide dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose
measure: Maximum Plasma Concentration (Cmax) of Rosuvastatin, Sildenafil and Furosemide.
timeFrame: Before rosuvastatin dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before sildenafil dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before furosemide dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose
measure: Tmax of Rosuvastatin, Sildenafil and Furosemide.
timeFrame: Before rosuvastatin dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before sildenafil dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before furosemide dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose
measure: T1/2 of Rosuvastatin, Sildenafil and Furosemide.
timeFrame: Before rosuvastatin dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before sildenafil dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before furosemide dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose
measure: AUC0-inf of Unchanged Edaravone.
timeFrame: Group 1 (Day 6, 9 and 12) and Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
measure: Cmax of Unchanged Edaravone.
timeFrame: Group 1 (Day 6, 9 and 12) and Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
measure: Tmax of Unchanged Edaravone.
timeFrame: Group 1 (Day 6, 9 and 12) and Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
measure: T1/2 of Unchanged Edaravone.
timeFrame: Group 1 (Day 6, 9 and 12) and Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
measure: AUC0-inf of Sulfate Conjugate.
timeFrame: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
measure: Cmax of Sulfate Conjugate.
timeFrame: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
measure: Tmax of Sulfate Conjugate.
timeFrame: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
measure: T1/2 of Sulfate Conjugate.
timeFrame: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
measure: AUC0-inf of Glucuronide Conjugate.
timeFrame: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
measure: Cmax of Glucuronide Conjugate.
timeFrame: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
measure: Tmax of Glucuronide Conjugate.
timeFrame: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
measure: T1/2 of Glucuronide Conjugate.
timeFrame: Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
measure: AUC0-inf of Unchanged Edaravone.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
measure: Cmax of Unchanged Edaravone.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
measure: Tmax of Unchanged Edaravone.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
measure: T1/2 of Unchanged Edaravone.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
measure: AUCinf of Sulfate Conjugate and Glucuronide Conjugate.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
measure: Cmax of Sulfate Conjugate and Glucuronide Conjugate.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
measure: Tmax of Sulfate Conjugate and Glucuronide Conjugate.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
measure: T1/2 of Sulfate Conjugate and Glucuronide Conjugate.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
measure: T1/2 of Glucuronide Conjugate.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
measure: Number of Participants With Adverse Events and Adverse Drug Reactions
timeFrame: 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
Secondary outcomes:
measure: AUCinf of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
measure: Cmax of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
measure: Tmax of Unchanged Edaravone.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
measure: T1/2 of Unchanged Edaravone.
timeFrame: Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: Investigational site
Study officials:
affiliation: Mitsubishi Tanabe Pharma Corporation
name: General Manager
role: STUDY_DIRECTOR
References:
citation: Shimizu H, Nishimura Y, Shiide Y, Akimoto M, Matsuda H, Kato Y, Hirai M. Food Effect Study to Assess the Impact on Edaravone Pharmacokinetic Profiles in Healthy Participants. Clin Ther. 2022 Dec;44(12):1552-1565. doi: 10.1016/j.clinthera.2022.10.001. Epub 2022 Nov 12.
citation: Shimizu H, Nishimura Y, Shiide Y, Matsuda H, Akimoto M, Matsuda M, Nakamaru Y, Kato Y, Kondo K. Evaluation of Pharmacokinetics, Safety, and Drug-Drug Interactions of an Oral Suspension of Edaravone in Healthy Adults. Clin Pharmacol Drug Dev. 2021 Oct;10(10):1174-1187. doi: 10.1002/cpdd.925. Epub 2021 Mar 11.