Comparative Bioavailability Study of Oral Edaravone Administered Orally and Via a Nasogastric Tube

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Adult Subjects
• Intervention / Treatment: Drug: MT-1186

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Toshima-ku
    • Tokyo, Toshima-ku, Japan, 171-0014
      • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MT-1186 orally; Subjects receive the edaravone oral suspension orally.	Drug: MT-1186; Suspension; Other Names: Edaravone
Experimental: MT-1186 via a nasogastric tube; Subjects receive the edaravone oral suspension via a nasogastric tube	Drug: MT-1186; Suspension; Other Names: Edaravone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration Versus Time Curve (AUC) of Edaravone	Area under the plasma concentration versus time curve from time zero up to the last quantifiable concentration time-point (AUC0-t) of edaravone, and Area under the plasma concentration versus time curve from time zero up to infinity with extrapolation of the terminal phase (AUC0-inf) of edaravone.	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.
Maximum Plasma Concentration (Cmax) of Edaravone		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.
Time to Reach Maximum Plasma Concentration (Tmax) of Edaravone		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.
Terminal Elimination Half-life (t1/2) of Edaravone		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.
Apparent Terminal Elimination Rate Constant (Kel) of Edaravone		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.
Mean Residence Time (MRT) of Edaravone		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.
Apparent Total Clearance (CL/F) of Edaravone		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.
Apparent Distribution Volume at Elimination Phase (Vz/F) of Edaravone		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.
Apparent Distribution Volume at Steady State (Vss/F) of Edaravone		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 Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events and Adverse Drug Reactions	Day 1 to 11

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation
• Investigators: Study Director: General Manager, Mitsubishi Tanabe Pharma Corporation

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2021
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): April 16, 2021

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neuroprotective Agents; Protective Agents; Antioxidants; Free Radical Scavengers; Edaravone
• Other Study ID Numbers: MT-1186-Z-101; jRCT2031200361 (Registry Identifier: Japan Registry of Clinical Trials (jRCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No