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

Healthy Adult Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05342597
• Other study ID #: MT-1186-J06
• Status: Completed
• Phase: Phase 1
• Start date: June 10, 2019
• Est. completion date: July 24, 2019

Study information

• Verified date: March 2023
• Source: Mitsubishi Tanabe Pharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: July 24, 2019
• Est. primary completion date: July 24, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Adult Subjects

Intervention

Drug:
• MT-1186
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.

Locations

Country	Name	City	State
Japan	Investigational site	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma Corporation

Country where clinical trial is conducted

Japan, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration Versus Time Curve From Zero up to Infinity (AUC0-inf) of Edaravone		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
Primary	Maximum Plasma Concentration (Cmax) of Edaravone		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
Primary	AUC0-inf of Sulfate Conjugate and Glucuronide Conjugate		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
Primary	Cmax of Sulfate Conjugate and Glucuronide Conjugate		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
Primary	Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate		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
Primary	Terminal Elimination Half-life (t1/2) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate		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
Primary	Apparent Terminal Elimination Rate Constant (Kel) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate		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
Primary	Mean Residence Time (MRT) of Unchanged Edaravone		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
Primary	Apparent Total Clearance (CL/F) of Unchanged Edaravone		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
Primary	Apparent Distribution Volume at Elimination Phase (Vz/F) of Unchanged Edaravone		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
Primary	Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone		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
Primary	Cumulative Urinary Excretion Amount (Ae 0-24h) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate		Day 1 to 9, Day 24 to 26
Primary	Urinary Excretion Ratio (Ae% 0-24h) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate		Day 1 to 9, Day 24 to 26
Primary	Renal Clearance (CLr) of Unchanged Edaravone		Day 1 to 9, Day 24 to 26
Secondary	Number of Participants With Adverse Events and Adverse Drug Reactions		Day 1 to Day 31