A Study to Evaluate the Effect of MCI-186 at Therapeutic and Supra-Therapeutic Doses on the QT Interval(QT)/Corrected QT Interval(QTc) Interval in Healthy Subjects

NCT04029090 | Completed Phase 1 Results FDA Drug

• 1 other identifier: MCI-186-J25
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the effect of MCI-186 on the QT interval corrected for heart rate using Fridericia's formula (QTcF)

Conditions

Healthy Adult Subjects

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in QTcF(ΔQTcF) With Placebo Adjustment (ΔΔQTcF) at Cmax of MCI-186

  The primary outcome endpoint was based on an analysis of the regression relationship between ΔQTcF and the concentration of MCI-186 at matching times post-dose, including adjustment for placebo treatments.

  45 min pre-dose to 24 h post-dose

Secondary Outcomes (8)

• Change From Baseline of Heart Rate(HR) by Timepoint

  Pre-dose to 24h post-dose

• Change From Baseline of PR Interval by Timepoint

  Pre-dose to 24h post-dose

• Change From Baseline of QRS Interval by Timepoint

  Pre-dose to 24h post-dose

• Change From Baseline of QTcF by Timepoint

  Pre-dose to 24h post-dose

• Plasma Concentration of MCI-186

  Pre-dose to 24h post-dose

Study Arms (3)

Sequence 1

EXPERIMENTAL

Subjects will receive a single intravenous dose of MCI-186 as a 1-hour infusion in the treatment sequence: first Treatment A, then Treatment C, then Treatment B (Treatment A= 60 mg of MCI-186, Treatment B= 300 mg of MCI-186, treatment C=0.9% w/v saline)

Drug: MCI-186; Drug: Placebo

Sequence 2

EXPERIMENTAL

Subjects will receive a single intravenous dose of MCI-186 as a 1-hour infusion in the treatment sequence: first Treatment B, then Treatment A, then Treatment C (Treatment A= 60 mg of MCI-186, Treatment B= 300 mg of MCI-186, treatment C=0.9% w/v saline)

Drug: MCI-186; Drug: Placebo

Sequence 3

EXPERIMENTAL

Subjects will receive a single intravenous dose of MCI-186 as a 1-hour infusion in the treatment sequence: first Treatment C, then Treatment B, then Treatment A (Treatment A= 60 mg of MCI-186, Treatment B= 300 mg of MCI-186, treatment C=0.9% w/v saline)

Drug: MCI-186; Drug: Placebo

Interventions

Placebo DRUG

A single dose of 0.9% w/v saline over 60 min will be intravenously administered.

Sequence 1; Sequence 2; Sequence 3

MCI-186 DRUG

A single dose of 60 mg MCI-186 over 60 min will be intravenously administered.

Also known as: Edaravone

Sequence 1; Sequence 2; Sequence 3

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males aged 20 to 55 years (both inclusive) at signature of the Informed Consent Form (ICF).
• Able to provide written informed consent to participate in this study after reading the ICF, and after having the opportunity to discuss the study with the Investigator or designee, before any screening or study related procedures take place.
• In the Investigator's opinion, subject is able to understand the nature of the study and any risks involved in participation, and willing to cooperate and comply with the protocol restrictions and requirements.
• A body weight of ≥45 kg and a body mass index (BMI) ranging from 18 to 30 kg/m2 (both inclusive) at screening and Day -1.
• Good health and free from clinically significant illness or disease in the opinion of the investigator on the basis of a physical examination, medical history, ECG, vital sign, and clinical laboratory test (biochemistry, hematology, coagulation and urinalysis) at screening and Day -1.
• Male subjects must practice effective contraception during the study, from the time of the first dose of Investigational Medicinal Product (IMP) until 14 days after the last dose of IMP.

You may not qualify if:

• Subjects with PR \>240 msec, QRS ≥120 msec, or QTcF \>450 msec on the screening or Day -1 ECG, or any clinically significant electrocardiographic abnormality in the opinion of the Investigator.
• Subject who has a history of cardiac disease or arrhythmias that can cause QTc prolongation.
• Subject who has a family history of Torsade de Pointes, long-QT syndrome, hypokalemia or sudden death.
• Subjects with potassium levels outside of the laboratory reference ranges at screening or Day -1.
• Subjects with clinically significant deviations from normal in physical examination, vital signs, ECG or clinical laboratory test at screening or Day -1 in the opinion of the Investigator.
• Presence or history of any clinically significant disease or organ dysfunction in the opinion of the Investigator.
• Presence or history of allergy to food, any medical product or relevant excipient that is of clinical significant.
• Subjects were previously administered MCI-186.
• Presence or history of alcohol abuse or a positive alcohol test.
• Presence or history of drug abuse or a positive drug screen test.
• Positive test for hepatitis C virus antibody, hepatitis B surface antigen, human immunodeficiency virus (HIV) antigen/antibody or syphilis test at screening.
• Participation in another trial within 12 weeks or 5 times the half-life of the drug whichever is longer before providing a signed ICF. For biologics, the minimum period is at least 24 weeks or the period of the pharmacodynamic effect, or 10 times the half-life of the drug, whichever is longer before providing a signed ICF.
• Donate blood more than 200 mL within 4 weeks, 400 mL within 12 weeks or 1000 mL within 52 weeks, respectively before providing a signed ICF.
• Donate plasma or platelet component within 2 weeks before providing a signed ICF.
• Use of any prescription or non-prescription medications including herbal remedies and vitamin/mineral/protein supplements, except for acetylsalicylic acid, within 7 days prior to IMPs dosing.

Sponsors & Collaborators

• Tanabe Pharma Corporation: lead

Study Sites (1)

Investigational site

Tokyo, Japan

Location

Related Publications (1)

• Shimizu H, Inoue S, Endo M, Nakamaru Y, Yoshida K, Natori T, Kakubari M, Akimoto M, Kondo K. A Randomized, Single-Blind, Placebo-Controlled, 3-Way Crossover Study to Evaluate the Effect of Therapeutic and Supratherapeutic Doses of Edaravone on QT/QTc Interval in Healthy Subjects. Clin Pharmacol Drug Dev. 2021 Jan;10(1):46-56. doi: 10.1002/cpdd.814. Epub 2020 Jun 15.

  PMID: 32543120 RESULT

MeSH Terms

Interventions

Edaravone

Intervention Hierarchy (Ancestors)

Antipyrine; Pyrazolones; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Clinical Trials, Information Desk
• Organization: Tanabe Pharma Corporation

cti-inq-ml.JP@ml.tanabe-pharma.com

+81-120-753-280

Study Officials

• General Manager

  Tanabe Pharma Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: This study is a single-blind study. Subjects and Electrocardiogram (ECG) reviewer will be blinded. Investigator and Sponsor will be unblinded.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 23, 2019
• Study Start: September 18, 2018
• Primary Completion: October 20, 2018
• Study Completion: October 23, 2018
• Last Updated: March 17, 2026
• Results First Posted: November 21, 2024

Record last verified: 2026-03

Locations

JP (1)