A Phase 1, Randomized, Double-blind, Sponsor-Open, Placebo- and Positive-Controlled Crossover Study to Investigate the Effect of Multiple Doses of Sisunatovir on QTc Interval in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Placebo-Adjusted Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) at Expected Maximum Concentration (Cmax) on Day 3 for Sisunatovir
研究概览
简要总结
The purpose of the study is to investigate the effects of multiple oral doses of sisunatovir on QTc Interval.
This study is seeking participants who:
- are male or female of 18 years of age or older
- are examined to be healthy All participants will receive Treatment A, B, and C in a randomized order based on 6 possible sequences. All treatments will be taken by mouth. Participants assigned to treatment A will receive 5 oral doses of sisunatovir administered Q12 hours over 3 days in a fed state. Participants assigned to treatment B will receive 5 oral doses of matching placebo administered Q12 hours over 3 days in a fed state. Participants assigned to treatment C will receive 4 oral doses of placebo administered Q12 hours for 2 days followed by a single dose of 400 mg moxifloxacin on the morning of Day 3.
All participants will remain in the study clinic for 4 days for each treatment, for safety review, laboratory collections, and to assess how the study medicine affects QTc intervals.
All participants selected in the study will be required to go through a screening period up to 28 days. A screening period is the time during which a few participants are examined to see whether they are fit for the study. During this period, the participant's medical history and past and current medications will be reviewed. A series of tests will also be performed to see if they are good to be selected for the study. If the participant meets all required criteria and are interested in continuing, the participant will be brought into the study clinic to stay overnight for 4 days for each treatment. On day 4, the participant will be discharged. About 28 to 35 days after discharge following the final treatment, the participant will be contacted for a follow up visit either in person or by telephone. This is to check up on how the participant is doing and to conclude the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Sisunatovir and placebo oral capsules will be prepared in the CRU by 2 operators, 1 of whom is an unblinded pharmacist. Sisunatovir and placebo will be administered in blinded fashion to the subject.
Moxifloxacin 400 mg tablets will be packaged in an open-label manner at the CRU in the individual dosing containers by 2 operators, 1 of whom is an appropriately qualified and experienced member of the study staff (eg, physician, nurse, physician's assistant, practitioner, or pharmacist).
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for healthy volunteers:
- •Body Mass Index (BMI) of 17.5 to 32 kg/m2, inclusive, and a total body weight >50 kg (110 lb).
- •Capable of giving signed informed consent.
- •At screening, no clinically relevant abnormalities identified by a detailed medical history, complete physical examination, including blood pressure (BP) and pulse rate measurement, standard 12-lead electrocardiogram (ECG) and clinical laboratory tests.
- •-Exclusion criteria for all participants:
- •Any condition or surgery possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection)
- •Those with increased risk if dosed with moxifloxacin
- •Self-reported history or risk factors for QT prolongation or torsades de pointes, congenital deafness, family history of cardiac arrest or suggest death, and family history of long QT syndrome
- •Positive human immunodeficiency virus (HIV) antibodies
- •Positive drug or alcohol test
- •Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility-estimated glomerular filtration rate (GFR) <60 mL/min/1.73m2 at screening
- •Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF >450 ms, complete LBBB, signs of an acute or indeterminate- age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third- degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT interval is >450 ms, this interval should be rate-corrected using the Fridericia method only and the resulting QTcF should be used for decision making and reporting. If QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice and the average of the 3 QTcF or QRS values used to determine the participant's eligibility. Participants with an average QTc interval >450 milliseconds (ms) will not be allowed to participate in the study. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding a participant.
- •GFR <60 mL/min/1.73m2 based on CKD-EPI equation
- •AST or ALT level ≥1.5 x upper limit normal (ULN)
- •Gamma-GT> 1.2 x ULN
- •Alkaline phosphatase > 1.2 x ULN
- •Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN
- •History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine).
排除标准
- 未提供
研究组 & 干预措施
Treatment A
6 capsules of sisunatovir administered Q12 hours for 5 doses
干预措施: sisunatovir (Drug)
Treatment B
6 capsules of placebo administered Q12 hours for 5 doses
干预措施: placebo (Drug)
Treatment C
6 capsules of placebo administered Q12 hours for 4 doses, followed by a single tablet of moxifloxacin
干预措施: moxifloxacin (Drug)
Treatment D
7 capsules of sisunatovir administered Q12 hours for 5 doses
干预措施: sisunatovir (Drug)
结局指标
主要结局
Placebo-Adjusted Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) at Expected Maximum Concentration (Cmax) on Day 3 for Sisunatovir
时间窗: Baseline, Day 3
The relationship between sisunatovir plasma concentration and change from baseline in Fridericia's heart-rate corrected QT interval were analyzed using a model-based concentration-QTc analysis consistent with the Scientific White Paper on Concentration-QT Modeling. Baseline was defined as the mean of the 3 averages of the triplicate electrocardiogram (ECG) measurements taken before dosing on Day 1 within each period. Mean and CI statistics were based on the individual (within subject) corrected differences between sisunatovir and placebo exposures.
次要结局
- Number of Participants With Treatment Emergent Adverse Events(From start of treatment on Day 1 up to 38 days after last dose of study drug (maximum up to 10 weeks))
- Number of Participants With Clinically Significant Changes in Electrocardiogram Parameters(From Baseline up to Day 23)
- Number of Participants Meeting Pre-defined Criteria for Vital Signs(From Baseline up to Day 23)
- Number of Participants With Clinically Significant Changes in Laboratory Abnormalities(From Baseline up to Day 23)
- Change From Baseline in QTcF of Moxifloxacin and Placebo at 3, 4 and 5 Hours Post-Dose of Day 3(Baseline, 3, 4 and 5 hours post-dose on Day 3)