A Randomized, Double-Blind, Placebo-Controlled, Single-Dose Escalation Study to Evaluate the Pharmacokinetics and the Effect on Cardiac Repolarization of Odalasvir Administered as a Tablet Formulation Under Fed Conditions in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 主要终点
- The Relationship Between the Plasma Concentrations of Odalasvir and Changes in the QT/QTc Interval Using Exposure-response (ER) Analysis
研究概览
简要总结
The purpose of this study is to determine the relationship between the plasma concentrations of odalasvir and changes in the QT interval / QTc interval (QT corrected for heart rate) using exposure-response (ER) analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
- •Participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
- •Participant must be healthy on the basis of physical examination, medical history, and vital signs performed at screening
- •Participant must have a blood pressure (after the participant is supine for 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic
- •Participant must have normal 12-lead electrocardiogram (ECG) and echocardiogram and must be healthy on the basis of clinical laboratory tests performed at screening
- •Participant must be nonsmoker for at least 6 months prior to study drug administration
排除标准
- •Participant with a history of clinically relevant heart rhythm disturbances including atrial, junctional, re-entry, and ventricular tachycardia, and heart blocks
- •Participant with unusual T wave morphology (such as bifid T wave) likely to interfere with QTc measurements
- •Participant with a past history of: Sick sinus syndrome, Cardiac arrhythmia (example, extrasystolic rhythms or tachycardia at rest). Isolated extrasystolic beats are not exclusionary, Risk factors associated with Torsade de Pointes (TdP) such as hypokalemia, Family history of short/long QT syndrome, Sudden unexplained death (including sudden infant death syndrome) in a first-degree relative (that is, sibling, offspring, or biological parent)
- •Participant with any skin condition likely to interfere with ECG electrode placement or adhesion
- •Participant with a breast implant or a history of thoracic surgery likely to cause abnormality of the electrical conduction through thoracic tissues
- •Participant with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
- •Participant has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 30 days or within a period less than 10 times the drug's half-life, whichever is longer, before the planned administration of study drug, or is currently enrolled in an investigational study
- •Participant has a history of human immunodeficiency virus (HIV)-1 or HIV-2 infection positive, or tests positive for HIV-1 or HIV-2 at screening
研究组 & 干预措施
Treatment A
Participants will receive odalasvir 100 milligram (mg) or odalasvir matching placebo once on Day 1.
干预措施: Odalasvir 100 mg (Drug)
Treatment A
Participants will receive odalasvir 100 milligram (mg) or odalasvir matching placebo once on Day 1.
干预措施: Placebo (Drug)
Treatment B
Participants will receive odalasvir 500 mg or odalasvir matching placebo once on Day 1.
干预措施: Placebo (Drug)
Treatment B
Participants will receive odalasvir 500 mg or odalasvir matching placebo once on Day 1.
干预措施: Odalasvir 500 mg (Drug)
Treatment C
Participants will receive odalasvir (dose to be determined based on pharmacokinetic data from treatment A and B but no more than 1000 mg) or odalasvir matching placebo once on Day 1.
干预措施: Placebo (Drug)
Treatment C
Participants will receive odalasvir (dose to be determined based on pharmacokinetic data from treatment A and B but no more than 1000 mg) or odalasvir matching placebo once on Day 1.
干预措施: Odalasvir (Up to maximum 1000 mg) (Drug)
结局指标
主要结局
The Relationship Between the Plasma Concentrations of Odalasvir and Changes in the QT/QTc Interval Using Exposure-response (ER) Analysis
时间窗: Baseline up to Day 4
A linear mixed-effects model will assess the effect of dose and treatment on the change from baseline in QTc over time.
次要结局
- Maximum Plasma Concentration (Cmax) of Odalasvir(0 hour (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 30, 36, 48, 72 and 120 hours post-dose on Day 1)
- Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Odalasvir(0 hour (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 30, 36, 48, 72 and 120 hours post-dose on Day 1)
- Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Odalasvir(0 hour (pre-dose) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 30, 36, 48, 72 and 120 hours post-dose on Day 1)
- PR Interval Changes and the Relationship Between the Plasma Concentrations of Odalasvir and PR Interval Changes Using ER Analysis(Baseline up to Day 4)
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability(up to Day 65)