A Randomized, Double-Blind, Parallel, Nested Crossover Study to Investigate the Effect of JNJ-64565111 on Cardiac Repolarization (Corrected QT Interval) Compared With Placebo in Healthy Adults: a Thorough ECG Study Employing Placebo, JNJ-64565111, and a Positive Control (Moxifloxacin)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 188
- 试验地点
- 1
- 主要终点
- Placebo-Corrected Change from Baseline in QT Interval Corrected for Individual Heart Rate (QTcI) on Day 26 Time-Matched Time Points
研究概览
简要总结
The purpose of this study is to assess the effects on placebo-corrected change from baseline QT interval corrected for individual heart rate (QTcI) of JNJ-64565111 close to steady state on Day 26 and on electrocardiogram morphology at supratherapeutic exposures in otherwise healthy overweight/obese adults after 4 weeks of treatment with JNJ 64565111 administered subcutaneously once weekly.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Body mass index (BMI) between 25.0 and 40.0 kilogram per square meter ( kg/m^2), inclusive, and a body weight of not less than 80 kg
- •Blood pressure (BP) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic
- •If a woman, must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening
- •If a woman, must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study (from screening through Day 56) or until 30 days after the last dose of study drug for participants that withdraw early from the study
- •QRS interval of less than or equal to (<=) 110 milliseconds (ms)
- •An average of triplicate 12-lead safety electrocardiogram (ECG) recording, completed within 4 minutes total, consistent with normal cardiac conduction and function at screening, including
- •Normal sinus rhythm (heart rate between 45 and 100 beats per minute [inclusive])
- •QT interval corrected for heart rate according to Fridericia's formula (QTcF) interval between 350 to 450 ms (inclusive)
- •PR interval <= 200 ms
- •ECG morphology consistent with healthy cardiac conduction and function
排除标准
- •Taken any disallowed therapies as defined in a protocol before the planned first dose of study drug
- •Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or at admission to the study
- •Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram at screening or at admission to the study site
- •Known allergies, hypersensitivity, or intolerance to JNJ-64565111, moxifloxacin, or its excipients
- •Hepatitis B or C infection
- •History of additional risk factors for torsade de pointes or the presence of a family history of Short QT Syndrome, Long QT Syndrome, sudden unexplained death at a young age (<= 40 years), or sudden infant death syndrome in a first-degree relative (that is biological parent, sibling, or child)
研究组 & 干预措施
Treatment Group 1: JNJ-64565111+Moxifloxacin Placebo
Participant will receive JNJ-64565111 on days 2, 9, 16, and 23 and moxifloxacin-matching placebo on days 1 and 27.
干预措施: JNJ-64565111 (Drug)
Treatment Group 1: JNJ-64565111+Moxifloxacin Placebo
Participant will receive JNJ-64565111 on days 2, 9, 16, and 23 and moxifloxacin-matching placebo on days 1 and 27.
干预措施: Moxifloxacin-matching Placebo (Drug)
Treatment Group 2: JNJ-64565111 Matching Placebo+Moxifloxacin
Participant will receive JNJ-64565111-matching placebo on days 2, 9, 16, and 23. Participants will also receive moxifloxacin on day 1 and moxifloxacin-matching placebo on day 27 (sequence 2a) or moxifloxacin-matching placebo on day 1 and moxifloxacin on day 27 (sequence 2b) in a nested crossover manner.
干预措施: Moxifloxacin (Drug)
Treatment Group 2: JNJ-64565111 Matching Placebo+Moxifloxacin
Participant will receive JNJ-64565111-matching placebo on days 2, 9, 16, and 23. Participants will also receive moxifloxacin on day 1 and moxifloxacin-matching placebo on day 27 (sequence 2a) or moxifloxacin-matching placebo on day 1 and moxifloxacin on day 27 (sequence 2b) in a nested crossover manner.
干预措施: JNJ-64565111-matching Placebo (Drug)
Treatment Group 2: JNJ-64565111 Matching Placebo+Moxifloxacin
Participant will receive JNJ-64565111-matching placebo on days 2, 9, 16, and 23. Participants will also receive moxifloxacin on day 1 and moxifloxacin-matching placebo on day 27 (sequence 2a) or moxifloxacin-matching placebo on day 1 and moxifloxacin on day 27 (sequence 2b) in a nested crossover manner.
干预措施: Moxifloxacin-matching Placebo (Drug)
结局指标
主要结局
Placebo-Corrected Change from Baseline in QT Interval Corrected for Individual Heart Rate (QTcI) on Day 26 Time-Matched Time Points
时间窗: Baseline and Day 26
Placebo-corrected change from baseline in QT interval corrected for individual heart rate (QTcI) on day 26 time-matched time points will be determined. The mean change from baseline in QTcI for participants who receive placebo will be subtracted from the mean change from baseline in QTcI for participants on JNJ-64565111 at the same time point to generate placebo-corrected change from baseline in QTcI, which will be presented.
Change from Time-Matched Baseline in QTc Interval
时间窗: Up to Day 27
The QT interval corrected for heart rate (QTc interval) using Fridericia method will be measured by electrocardiograms (ECG).
Change from Time-Matched Baseline in Heart Rate (HR)
时间窗: Up to Day 27
The HR will be measured by ECG.
Change from Time-Matched Baseline in QRS Interval
时间窗: Up to Day 27
The QRS Intervals will be measured by ECG.
Change from Time-Matched Baseline in PR Interval
时间窗: Up to Day 27
The PR intervals will be measured by ECG.
次要结局
- Cardiac Repolarization as Determined by Mean Change from Time-Matched Baseline in QT Interval Corrected for Individual HR (QTcI) on Day 5(Baseline and Day 5)
- Cardiac Repolarization as Determined by Mean Change from Time-Matched Baseline in QT Interval Corrected For HR Using Fridericia's Formula (QTcF) on Day 5 and Day 26(Baseline, Day 5 and Day 26)
- Maximum Observed Serum Concentration (Cmax)(Days 1, 5, 26 and 27)
- Time to Reach Maximum Observed Serum Concentration (Tmax)(Days 1, 5, 26 and 27)
- Average Serum Analyte Concentration (Cavg)(Days 1, 5, 26 and 27)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(From signing of the informed consent form (ICF) to end of study (approximately 12 weeks))
- QTcI Changes Evaluated Using ECG Assessments versus Serum Concentrations of JNJ-64565111(Up to Day 27)