Study of Oral Edaravone in Healthy Adult Males

Shionogi74 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

SINGLE

Enrollment

Conditions

Healthy Adult Subjects

Interventions

MT-1186DRUG

Solution or suspension

MT-1186-matching placeboDRUG

Solution or suspension

Eligibility

Sex: MALEMin age: 20 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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 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

Locations (1)

Investigational Site

Osaka, Japan

Outcomes

Primary Outcomes

Number of Participants With Adverse Events (Aes) and Adverse Drug Reactions (ADRs)

Time frame: 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

Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of unchanged edaravone.

Time frame: 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 Sulfate Conjugate

Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of sulfate conjugate.

Area Under the Concentration Versus Time Curve (AUC) of Glucuronide Conjugate

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

Maximum Plasma Concentration (Cmax) of Sulfate Conjugate

Data from ClinicalTrials.gov

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Maximum Plasma Concentration (Cmax) of Glucuronide Conjugate

Part 2: Minimum Plasma Concentration at Steady State (Ctrough, ss)

Time frame: 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

Time to Reach Maximum Plasma Concentration (Tmax) of Sulfate Conjugate

Time to Reach Maximum Plasma Concentration (Tmax) of Glucuronide Conjugate

Terminal Elimination Half-life (t1/2) of Unchanged Edaravone

Terminal Elimination Half-life (t1/2) of Sulfate Conjugate

Terminal Elimination Half-life (t1/2) of Glucuronide Conjugate

Lambda-z of Unchanged Edaravone

Lambda-z of Sulfate Conjugate

Lambda-z of Glucuronide Conjugate

Mean Residence Time (MRT) of Unchanged Edaravone

Time frame: 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

Apparent Distribution Volume at Elimination Phase (Vz/F) and Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone

Secondary Outcomes

Change of Heart Rate (HR) From Baseline

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.

Time frame: 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.

Change of PR Interval (PR) From Baseline

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.

Time frame: 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.

Change of QTcF Interval (QTcF) From Baseline

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.

Time frame: 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.

Change of QRS Duration (QRS) From Baseline

Holter ECG data were recorded in part 1, Cohorts S4, S5, and S6.

Time frame: 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.