A Phase I Single Centre, Randomized, Double Blind (Except For Moxifloxacin), Placebo And Active Controlled, Four Way Cross Over Study Investigating The Effect Of Single Therapeutic And Supra Therapeutic Doses Of Fedovapagon On The QT/QTC Interval In Healthy Volunteers Using Oral Moxifloxacin To Confirm Assay Sensitivity
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Vantia Ltd
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Time-matched change from baseline in QTc, placebo-adjusted and corrected for heart rate
研究概览
简要总结
The purpose of this study is to assess the electrocardiogram (ECG) effects of fedovapagon dose administration relative to placebo in healthy adult male and female subjects.
详细描述
Regulatory guidance (ICH E14) has emphasized the need to obtain clear robust data on the effect of new chemical entities on ECG parameters with focus on cardiac repolarization as measured by the QTc duration. Though many Phase 1, 2 and 3 trials may be conducted they usually have insufficient sample size, infrequent sampling of ECG data, or the use of inadequate controls to overcome the high rate of spontaneous change in QTc duration. This has resulted in regulatory guidance recommending a dedicated or thorough trial to define the ECG effects of new drugs.
This study will be conducted in healthy volunteers to eliminate variables known to have an effect on ECG parameters (concomitant drugs, diseases, etc.). A supra-therapeutic dose of fedovapagon is required to mimic the exposure in healthy volunteers that may occur in the target population under the worst of circumstances (e.g., concomitant use of CYP3A4 inhibitor, concomitant liver disease, presence of heart disease, taking more than the clinical dose prescribed, etc.) and to allow for PK to QTc modeling to assess the effect of drug concentration on cardiac repolarization.
A cross-over trial is the preferred design as subjects act as their own controls and since there is no accumulation of any clinical relevance and the plasma concentration of parent dissipates before 24 hours, a single dose trial will be employed. During the course of the study each subject will be administered fedovapagon at both a clinical and supra-therapeutic dose, placebo and moxifloxacin (as a positive control).
The sample size is driven by the need to do a time-matched statistical analysis on the primary endpoint as per ICH E14 guidance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provide signed and dated informed consent before any study-specific procedures are conducted.
- •Healthy males and females 18 to 55 years of age (inclusive).
- •No clinically significant abnormal physical findings.
- •No clinically significant abnormal values for hematology, clinical chemistry or urinalysis at screening or admission.
- •Have a body mass index (BMI) ≥18.0 to ≤29.9 kg/m2 (weight: ≥50 kg and ≤100 kg) at the Screening visit.
- •Be judged by the Investigator to be in good health based on medical history, physical examination, vital sign measurements and laboratory safety tests performed at the Screening visit and before the first administration of fedovapagon, moxifloxacin or placebo.
- •Have no clinically significant abnormality on an ECG performed at the Screening visit and on admission to the study center.
- •Have a normal resting blood pressure.
- •Must be able to understand and be willing to comply with study procedures, restrictions and requirements.
- •Agree to refrain from the consumption of grapefruit or grapefruit juice beginning 1 week prior to administration of the initial administration fedovapagon, moxifloxacin or placebo, throughout the trial.
- •Agree to refrain from the consumption of alcohol and/or methylxanthines e.g., caffeine (coffee, tea and cola) beginning 96 hours prior to administration of the initial administration of fedovapagon, moxifloxacin or placebo, throughout the trial.
- •Current non-smokers who have not used any nicotine-containing products (chewed or smoked) or replacement products including electronic cigarettes in the 45 days prior to screening.
- •Woman of child-bearing potential must be using effective methods (failure rate <1%) of birth control at least 4 weeks prior to Screening until 4 weeks after the administration of fedovapagon, moxifloxacin or placebo.
- •Male subjects should be willing to use a condom with spermicide during sexual activity with female partners of child-bearing potential and must not donate sperm. Female sexual partners of male subjects should be willing to avoid pregnancy.
排除标准
- 未提供
研究组 & 干预措施
Moxifloxacin 400 mg (open label)
One dose of moxifloxacin 400 mg (open label)
干预措施: Moxifloxacin (Drug)
Placebo matched to fedovapagon
One dose of placebo (matched to fedovapagon)
干预措施: Placebo (for fedovapagon) (Drug)
Fedovapagon 2 mg
One dose of 2 mg fedovapagon
干预措施: Fedovapagon (Drug)
Fedovapagon 20 mg
One dose of 20 mg fedovapagon
干预措施: Fedovapagon (Drug)
结局指标
主要结局
Time-matched change from baseline in QTc, placebo-adjusted and corrected for heart rate
时间窗: 0-48 hours
次要结局
- Heart rate(0-48 hours)
- PR interval(0-48 hours)
- QRS interval(0-48 hours)
- Uncorrected QT interval(0-48 hours)
- ECG morphology especially on repolarization(0-48 hours)
- Correlation between the QTc change from baseline and plasma concentrations of fedovapagon(0-48 hours)
- Number and type of adverse events(0-48 hours)
- The observed maximum plasma concentration (Cmax)(0-48 hours)
- Time to reach maximum plasma concentration (tmax)(0-48 hours)
- Apparent terminal half-life (t½)(0-48 hours)
- Area under the plasma concentration-time curve (AUC0-t), (AUC0-24h) and (AUC0-∞)(0-48 hours)