Clinical trial NCT04776135: Comparative Bioavailability Study of Oral Edaravone Administered Orally and Via a Nasogastric Tube
Official title: A Phase I, Randomized, Open-Label, Crossover-Design, Single-Dose Study to Investigate the Safety, Tolerability and Comparative Bioavailability of Oral Edaravone Administered Orally and Via a Nasogastric Tube (NGT) in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adult Subjects
Lead sponsor: Mitsubishi Tanabe Pharma Corporation
Sponsor class: INDUSTRY
First posted: 2021-03-01
Enrollment: 36
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: To investigate the comparative bioavailability of edaravone oral suspension administered orally and via a nasogastric tube in healthy adult subjects


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 meet any of the following criteria between screening and investigational product administration will be 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 antigen, serological test for syphilis, hepatitis C virus antibody, or human immunodeficiency virus antigen/antibody, subject has a positive COVID-19 virus test on Day -1
6. Any clinically significant 12-lead ECG abnormality or 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, or blood donation and transfusion from informed consent to the start of investigational product administration
9. Subjects who have undergone any surgery known to affect the gastrointestinal absorption of drugs (except for appendectomy and herniotomy)
10. Female subjects of childbearing potential 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 alcohol or any products containing xanthin or caffeine within 24 hours before screening and visit on Day -1
15. Use of any nutritional supplement(s) within 7 days before the initiation of investigational product administration
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 with a history of reconstructive nasal surgery, or any evidence of deformities or asymmetry of the nose, non-patent nares/obstructed nasal airway, or the presence of nasal ulcers or polyps that would prevent an adequate NGT insertion.
20. 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 (AUC) of Edaravone
timeFrame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hours after administration.
measure: Maximum Plasma Concentration (Cmax) of Edaravone
timeFrame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Edaravone
timeFrame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
measure: Terminal Elimination Half-life (t1/2) of Edaravone
timeFrame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
measure: Apparent Terminal Elimination Rate Constant (Kel) of Edaravone
timeFrame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
measure: Mean Residence Time (MRT) of Edaravone
timeFrame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
measure: Apparent Total Clearance (CL/F) of Edaravone
timeFrame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
measure: Apparent Distribution Volume at Elimination Phase (Vz/F) of Edaravone
timeFrame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
measure: Apparent Distribution Volume at Steady State (Vss/F) of Edaravone
timeFrame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
Secondary outcomes:
measure: Number of Participants With Adverse Events and Adverse Drug Reactions
timeFrame: Day 1 to 11
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: Investigational site
state: Toshima-ku
Study officials:
affiliation: Mitsubishi Tanabe Pharma Corporation
name: General Manager
role: STUDY_DIRECTOR
References:
citation: Shimizu H, Nishimura Y, Shiide Y, Ueda M, Yokota S, Kato Y, Hirai M. Edaravone Administered Orally and Via Nasogastric Tube in Healthy Adults: A Comparative Bioavailability Phase 1 Study. Clin Pharmacol Drug Dev. 2023 Jan;12(1):77-84. doi: 10.1002/cpdd.1175. Epub 2022 Oct 12.