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

A Randomized, Single-Blind, Placebo-Controlled, Three-Way Crossover Study to Evaluate the Effect of MCI-186 at Therapeutic and Supra-Therapeutic Doses on the QT/QTc Interval in Healthy Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy Adult Subjects
• Intervention / Treatment: Drug: MCI-186; Drug: MCI-186; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Use of tobacco or nicotine containing products for 24 hours before each visit of screening or Day -1.
• Consumption of alcohol, xanthines, or grapefruit containing products for 24 hours before each visit of screening or Day -1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sequence 1; 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; A single dose of 60 mg MCI-186 over 60 min will be intravenously administered.; Other Names: Edaravone; Drug: MCI-186; A single dose of 300 mg MCI-186 over 60 min will be intravenously administered.; Other Names: Edaravone; Drug: Placebo; A single dose of 0.9% w/v saline over 60 min will be intravenously administered.
EXPERIMENTAL: Sequence 2; 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; A single dose of 60 mg MCI-186 over 60 min will be intravenously administered.; Other Names: Edaravone; Drug: MCI-186; A single dose of 300 mg MCI-186 over 60 min will be intravenously administered.; Other Names: Edaravone; Drug: Placebo; A single dose of 0.9% w/v saline over 60 min will be intravenously administered.
EXPERIMENTAL: Sequence 3; 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; A single dose of 60 mg MCI-186 over 60 min will be intravenously administered.; Other Names: Edaravone; Drug: MCI-186; A single dose of 300 mg MCI-186 over 60 min will be intravenously administered.; Other Names: Edaravone; Drug: Placebo; A single dose of 0.9% w/v saline over 60 min will be intravenously administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Relationship of change from baseline in QTcF (ΔQTcF) with placebo adjustment (ΔΔQTcF) and concentration of MCI-186	45 min pre-dose to 24 h post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Pharmacokinetic(PK) parameters - Area under the concentration versus time curve from time zero to infinity (AUC 0-inf) of MCI-186	Pre-dose to 24h post-dose
PK parameters - Maximum plasma concentration (Cmax) of MCI-186	Pre-dose to 24h post-dose
Incidence of adverse events (AEs)	Day 1 to 9

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 18, 2018
• Primary Completion (ACTUAL): October 20, 2018
• Study Completion (ACTUAL): October 23, 2018

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (ACTUAL): July 23, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neuroprotective Agents; Protective Agents; Antioxidants; Free Radical Scavengers; Edaravone
• Other Study ID Numbers: MCI-186-J25

Drug and device information, study documents

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