Clinical trial NCT05342597: Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Subjects (Food Effect Study)
Official title: Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Subjects (Food Effect Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adult Subjects
Lead sponsor: Mitsubishi Tanabe Pharma Corporation
Sponsor class: INDUSTRY
First posted: 2022-04-22
Enrollment: 16
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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 different meal contents and fasting condition.


Eligibility criteria: 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.

  1. Healthy adult male or female volunteers
  2. Japanese
  3. Subjects aged between 20 and 45 years at the time of informed consent
  4. 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:

  1. 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
  2. History of drug or food allergies
  3. History of alcohol or drug abuse or dependence
  4. Body mass index (BMI) of \< 18.0 or \> 30.0, or a body weight of \< 50 kg \[BMI formula: body weight (kg)/height (m)2, rounded to one decimal place\]
  5. 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
  6. Any clinically significant 12-lead ECG abnormality or corrected QT interval (QTc) using Fridericia's formula (QTcF) interval ≥ 450 msec
  7. 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
  8. Blood component donation or blood sampling within 2 weeks before providing informed consent
  9. Subjects who have undergone any surgery known to affect the gastrointestinal absorption of drugs (except for appendectomy and herniotomy)
  10. 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
  11. Subjects who have previously received edaravone
  12. Subjects who have participated in another clinical study and received an investigational product within 12 weeks before providing informed consent
  13. Subjects who have used any drugs other than the single use of acetylsalicylic acid within 7 days before the initiation of investigational product administration
  14. Use of any nutritional supplement(s) within 7 days before the initiation of investigational product administration
  15. Use of alcohol or any products containing xanthin or caffeine within 24 hours before screening and visit on Day -1
  16. Use of grapefruit, grapefruit juice, or any processed food(s) containing these substances within 24 hours before screening and visit on Day -1
  17. Use of any tobacco or nicotine-containing product(s) within 24 hours before screening and visit on Day -1
  18. 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
  19. Subjects judged by the investigator (or subinvestigator) to be unsuitable for the study for any other reason

Primary outcomes:
measure: Area Under the Concentration Versus Time Curve From Zero up to Infinity (AUC0-inf) of Edaravone
timeFrame: Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration
measure: Maximum Plasma Concentration (Cmax) of Edaravone
timeFrame: Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration
measure: AUC0-inf of Sulfate Conjugate and Glucuronide Conjugate
timeFrame: Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration
measure: Cmax of Sulfate Conjugate and Glucuronide Conjugate
timeFrame: Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate
timeFrame: Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration
measure: Terminal Elimination Half-life (t1/2) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate
timeFrame: Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration
measure: Apparent Terminal Elimination Rate Constant (Kel) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate
timeFrame: Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration
measure: Mean Residence Time (MRT) of Unchanged Edaravone
timeFrame: Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration
measure: Apparent Total Clearance (CL/F) of Unchanged Edaravone
timeFrame: Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration
measure: Apparent Distribution Volume at Elimination Phase (Vz/F) of Unchanged Edaravone
timeFrame: Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration
measure: Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone
timeFrame: Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration
measure: Cumulative Urinary Excretion Amount (Ae 0-24h) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate
timeFrame: Day 1 to 9, Day 24 to 26
measure: Urinary Excretion Ratio (Ae% 0-24h) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate
timeFrame: Day 1 to 9, Day 24 to 26
measure: Renal Clearance (CLr) of Unchanged Edaravone
timeFrame: Day 1 to 9, Day 24 to 26
Secondary outcomes:
measure: Number of Participants With Adverse Events and Adverse Drug Reactions
timeFrame: Day 1 to Day 31
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.