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

Healthy Adult Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04029090
• Other study ID #: MCI-186-J25
• Status: Completed
• Phase: Phase 1
• Start date: September 18, 2018
• Est. completion date: October 23, 2018

Study information

• Verified date: July 2019
• Source: Mitsubishi Tanabe Pharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: October 23, 2018
• Est. primary completion date: October 20, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Adult Subjects

Intervention

Drug:
• MCI-186
A single dose of 60 mg MCI-186 over 60 min will be intravenously administered.
• MCI-186
A single dose of 300 mg MCI-186 over 60 min will be intravenously administered.
• Placebo
A single dose of 0.9% w/v saline over 60 min will be intravenously administered.

Locations

Country	Name	City	State
Japan	Investigational site	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma Corporation

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relationship of change from baseline in QTcF (?QTcF) with placebo adjustment (??QTcF) and concentration of MCI-186		45 min pre-dose to 24 h post-dose
Secondary	Change from baseline of heart rate(HR) by timepoint		Pre-dose to 24h post-dose
Secondary	Change from baseline of PR interval by timepoint		Pre-dose to 24h post-dose
Secondary	Change from baseline of QRS interval by timepoint		Pre-dose to 24h post-dose
Secondary	Change from baseline of QTcF by timepoint		Pre-dose to 24h post-dose
Secondary	Plasma concentration of MCI-186		Pre-dose to 24h post-dose
Secondary	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
Secondary	PK parameters - Maximum plasma concentration (Cmax) of MCI-186		Pre-dose to 24h post-dose
Secondary	Incidence of adverse events (AEs)		Day 1 to 9