Study of Oral Edaravone in Healthy Adult Males

Phase 1

Completed

• Conditions: Healthy Adult Subjects
• Interventions: Drug: MT-1186; Drug: MT-1186-matching placebo

• Registration Number: NCT04481750
• Lead Sponsor: Mitsubishi Tanabe Pharma Corporation

Brief Summary

To evaluate the pharmacokinetics safety, and tolerability of single and multiple doses of edaravone solution and suspension in healthy adult males

Detailed Description

Not available

Study Timeline

• Study Start: 2018-03-20
• Primary Completion: 2018-08-03
• Study Completion: 2018-08-03
• Study First Submitted: 2020-07-17
• Study First Submitted QC: 2020-07-17
• Study First Posted: 2020-07-22
• Results First Submitted: 2023-05-12
• Status Verified: 2024-02
• Results First Submitted QC: 2024-02-15
• Last Update Submitted: 2024-02-15
• Results First Posted: 2024-08-02
• Last Update Posted: 2024-08-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 74

Inclusion Criteria

Additional screening criteria check may apply for qualification:

• Healthy adult male volunteers
• 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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A single dose MT-1186 (Part 1, Cohort S1)	MT-1186-matching placebo	Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S1)	MT-1186	Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S3-2)	MT-1186-matching placebo	Healthy Japanese male subjects receive doses of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S4)	MT-1186	Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S4)	MT-1186-matching placebo	Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S5)	MT-1186	Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S5)	MT-1186-matching placebo	Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S6)	MT-1186	Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S6)	MT-1186-matching placebo	Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S7)	MT-1186	Healthy Caucasian male subjects receive a single dose of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S7)	MT-1186-matching placebo	Healthy Caucasian male subjects receive a single dose of MT-1186 or matching placebo.
Multiple doses MT-1186 (Part 2, Cohort M1)	MT-1186	Healthy Japanese male subjects receive multiple doses of MT-1186 or matching placebo.
Multiple doses MT-1186 (Part 2, Cohort M1)	MT-1186-matching placebo	Healthy Japanese male subjects receive multiple doses of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S2)	MT-1186	Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S2)	MT-1186-matching placebo	Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S3-1)	MT-1186	Healthy Japanese male subjects receive doses of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S3-1)	MT-1186-matching placebo	Healthy Japanese male subjects receive doses of MT-1186 or matching placebo.
A single dose MT-1186 (Part 1, Cohort S3-2)	MT-1186	Healthy Japanese male subjects receive doses of MT-1186 or matching placebo.
Multiple doses MT-1186 (Part 2, Cohort M2)	MT-1186	Healthy Japanese male subjects receive multiple doses of MT-1186 or matching placebo
Multiple doses MT-1186 (Part 2, Cohort M2)	MT-1186-matching placebo	Healthy Japanese male subjects receive multiple doses of MT-1186 or matching placebo

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs)	Day 1 to 8 in Part 1, up to 12 days in Part 2
Area Under the Concentration Versus Time Curve (AUC) of Unchanged Edaravone	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5	Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of unchanged edaravone.
Area Under the Concentration Versus Time Curve (AUC) of Sulfate Conjugate	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5	Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of sulfate conjugate.
Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Part 2: Minimum Plasma Concentration at Steady State (Ctrough, ss)	Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5	Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of glucuronide conjugate.
Maximum Plasma Concentration (Cmax) of Unchanged Edaravone	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Maximum Plasma Concentration (Cmax) of Sulfate Conjugate	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Lambda-z of Unchanged Edaravone	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Lambda-z of Sulfate Conjugate	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Lambda-z of Glucuronide Conjugate	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Mean Residence Time (MRT) of Unchanged Edaravone	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Apparent Total Clearance (CL/F) of Unchanged Edaravone	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Terminal Elimination Half-life (t1/2) of Unchanged Edaravone	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5
Terminal Elimination Half-life (t1/2) of Sulfate Conjugate	Part 1: Pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs post-dose, Part 2: Day 1 and 5 at pre-dose, 0.25, 0.5, 1.5, 2, 4, 6, 8, 12 hrs post-dose; Day 2 to 4 at pre-dose; Day 6 at 24 hrs post-dose on Day 5; Day 7 at 48 hrs post-dose on Day 5

Secondary Outcome Measures

Name	Time	Method
Change of QTcF Interval (QTcF) From Baseline	0.75, 0.5, and 0.25 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose.	Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6. Baseline is calculated as average HR from 0.75, 0.5, and 0.25 hours pre-dose.
Change of QRS Duration (QRS) From Baseline	0.75, 0.5, and 0.25 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose.	Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6.
Change of Heart Rate (HR) From Baseline	0.75, 0.5, and 0.25 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose.	Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6. Baseline is calculated as average HR from 0.75, 0.5, and 0.25 hours pre-dose.
Change of PR Interval (PR) From Baseline	0.75, 0.5, and 0.25 hours pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose.	Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6. Baseline is calculated as average HR from 0.75, 0.5, and 0.25 hours pre-dose.

Trial Locations

Locations (1)

Investigational Site; 🇯🇵 Osaka, Japan