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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Change From Baseline in QTcF(ΔQTcF) With Placebo Adjustment (ΔΔQTcF) at Cmax of MCI-186
研究概览
简要总结
To evaluate the effect of MCI-186 on the QT interval corrected for heart rate using Fridericia's formula (QTcF)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
This study is a single-blind study. Subjects and Electrocardiogram (ECG) reviewer will be blinded. Investigator and Sponsor will be unblinded.
入排标准
- 年龄范围
- 20 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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 -
- •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 -
- •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.
排除标准
- •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 -
- •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-
- •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 -
- •Consumption of alcohol, xanthines, or grapefruit containing products for 24 hours before each visit of screening or Day -1.
研究组 & 干预措施
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)
干预措施: MCI-186 (Drug)
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)
干预措施: Placebo (Drug)
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)
干预措施: Placebo (Drug)
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)
干预措施: Placebo (Drug)
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)
干预措施: MCI-186 (Drug)
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)
干预措施: MCI-186 (Drug)
结局指标
主要结局
Change From Baseline in QTcF(ΔQTcF) With Placebo Adjustment (ΔΔQTcF) at Cmax of MCI-186
时间窗: 45 min pre-dose to 24 h post-dose
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.
次要结局
- 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)
- Number of Participants With Adverse Events (AEs)(Day 1 to 9)