Pharmacokinetics Study of MCI-186 in Subjects With Mild or Moderate Hepatic Impairment

A Multi-Center, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MCI-186 in Subjects With Mild or Moderate Hepatic Impairment Compared to Subjects With Normal Hepatic Function

To assess the pharmacokinetics of MCI-186 after a single intravenous infusion of 30mg/hour in subjects with mild or moderate Hepatic impairment compared to subjects with normal hepatic function

Study Overview

• Status: Completed
• Conditions: Healthy; Hepatic Impairment
• Intervention / Treatment: Drug: MCI-186

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Investigational Site
  • Tokyo, Japan
    • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All subjects

• Able to provide written informed consent to participate in this study after reading the ICF
• Subjects is able to understand and willing to cooperate and comply with the Protocol restrictions and requirements.
• A body weight of ≥45 kg in males or ≥40 kg in females and a body mass index ranging from 18 to 30 kg/m2

Hepatic impaired subjects (in addition)

• A Child-Pugh score of 5 or 6 for subjects with mild hepatic impairment, and between 7 and 9, inclusive, for subjects with moderate hepatic impairment
• Chronic and stable hepatic impairment

Healthy subjects (in addition)

• Subject with normal hepatic function
• Good health and free from clinically significant illness or disease

Exclusion Criteria:

All subjects

• Presence or history of severe allergy to food, or any medicinal product or relevant excipient that is of clinical significance
• Subjects were previously administered MCI-186.
• Positive urine drug screen (if not due to concomitant medication) or alcohol test
• History of drug abuse
• Presence of alcohol abuse
• Presence of active infection requiring antibiotics
• Positive test for human immunodeficiency virus (HIV) antigen/antibody
• Uncontrolled, or untreated hypertension defined as systolic blood pressure (SBP)>160 mmHg and/or diastolic blood pressure (DBP)>100 mmHg
• eGFR <60 mL/min/1.73m2

Hepatic impairment subject (in addition)

• Subjects with severe ascites

Healthy subject (in addition)

• History or presence of any parenchymal hepatic disease
• Positive test for hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mild hepatic impairment	Drug: MCI-186; 30 mg of edaravone will be administered intravenously over 60 minutes; Other Names: Edaravone; Radicut
Experimental: moderate hepatic impairment	Drug: MCI-186; 30 mg of edaravone will be administered intravenously over 60 minutes; Other Names: Edaravone; Radicut
Experimental: normal hepatic function	Drug: MCI-186; 30 mg of edaravone will be administered intravenously over 60 minutes; Other Names: Edaravone; Radicut

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax	pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h and 48h post-dose
AUC0-last	pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h and 48h post-dose
AUC0-∞	pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h and 48h post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
t½	pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h and 48h post-dose

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Nakamaru Y, Kakubari M, Yoshida K, Akimoto M, Todorovic V, Greis T, Kondo K. Open-label, Single-dose Studies of the Pharmacokinetics of Edaravone in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared to Subjects with Normal Hepatic Functioning. Clin Ther. 2020 Aug;42(8):1467-1482.e4. doi: 10.1016/j.clinthera.2020.06.016. Epub 2020 Aug 14.

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2016
• Primary Completion (Actual): July 20, 2018
• Study Completion (Actual): July 24, 2018

Study Registration Dates

• First Submitted: September 19, 2017
• First Submitted That Met QC Criteria: September 19, 2017
• First Posted (Actual): September 20, 2017

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neuroprotective Agents; Protective Agents; Antioxidants; Free Radical Scavengers; Edaravone
• Other Study ID Numbers: MCI-186-J23

Drug and device information, study documents

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