A Randomized, Double-blind, Placebo- and Positive-controlled, Single-dose, 4-way Crossover Study to Evaluate the Effects of Seltorexant (JNJ-42847922) on Electrocardiogram Intervals in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Percentage of Participants with Change from Baseline in T-wave Morphology
研究概览
简要总结
The purpose of this study is to assess the effects of single dose seltorexant on QT/QTc intervals and electrocardiogram (ECG) morphology at therapeutic and supratherapeutic exposures in healthy adult participants.
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
- Quadruple (Participant, Care Provider, 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
- •Have signed informed consent form (ICF) indicating they understand the purpose of and procedures required for the study, including the required pharmacogenomic component (which specifies testing of genes predisposing to long or short QT and related cardiac syndromes), and are willing to participate in the study. Consent for sample storage will be obtained in the ICF
- •Be Willing to adhere to the prohibitions and restrictions specified in the protocol
- •A female participant must be either not of childbearing potential (ie, postmenopausal, permanently sterile) or of childbearing potential and practicing a highly effective method of contraception (failure rate of less than [<]1 percent [%] per year when used consistently and correctly)
- •A female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 1 month after the last study drug administration
- •A male participant, who is sexually active with a woman of childbearing potential and has not had a vasectomy, must agree to use an adequate contraception method as deemed appropriate by the investigator (eg, vasectomy, double-barrier, partner using effective contraception) and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
- •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. Heart rate between 45 and 100 beats per minute (bpm), inclusive
排除标准
- •Clinically significant abnormal values for hematology, serum chemistry (including thyroid stimulating hormone [TSH] at screening only) or urinalysis at screening or at admission to the study site
- •Clinically significant abnormal physical examination, vital signs, or 12-lead electrocardiogram (ECG) at screening or at admission to the study site as deemed appropriate by the investigator
- •Received a known inhibitor of CYP3A4 or CYP2C9 activity within 14 days or a period less than 5 times the drugs' half-life; whichever is longer, before the first dose of the study drug is scheduled
- •Known allergy to the study drug or any of the excipients of the formulation
- •Received an experimental drug or used an experimental medical device within 1 month or within a period less than 10 times the drug's half-life, whichever is longer, before the first dose of the study drug is scheduled
- •A woman who is pregnant, breast-feeding, or planning to become pregnant during the study
研究组 & 干预措施
Seltorexant (Low and high dose)
Participants will receive seltorexant tablets orally in 2 of 4 treatment arms (A,B,C,D) in a cross-over design, with 7 days wash-out phase between each treatment period.
干预措施: Seltorexant (Drug)
Moxifloxacin
Participants will receive moxifloxacin tablets orally in 1 of 4 treatment arms (A,B,C,D) in a cross-over design, with 7 days wash-out phase between each treatment period.
干预措施: Moxifloxacin Dose 1 (Drug)
Placebo Matched to Seltorexant
Participants will receive seltorexant placebo tablets orally in 3 of 4 treatment arms (A,B,C,D) in a cross-over design, with 7 days wash-out phase between each treatment period.
干预措施: Placebo Matched to Seltorexant (Other)
Placebo Matched to Moxifloxacin
Participants will receive moxifloxacin placebo tablets orally in 3 of 4 treatment arms (A,B,C,D) in a cross-over design, with 7 days wash-out phase between each treatment period.
干预措施: Placebo Matched to Moxifloxacin (Other)
结局指标
主要结局
Percentage of Participants with Change from Baseline in T-wave Morphology
时间窗: Baseline up to Day 3
The percentage of participants in each treatment having T-wave morphology changes from baseline that represent the appearance or worsening of the morphological abnormality will be reported.
Change From Baseline in QT/QTc Intervals
时间窗: Baseline up to Day 3
Change from baseline in QT and QTc interval will be assessed. QT interval will be measured in triplicates from 12 lead Holter extracted triplicate ECG recordings and corrected QT (QTc) interval will be calculated based on Fridericia (QTcF), Bazett (QTcB), and/or study specific power (QTcP) equations.
Percentage of Participants with Change from Baseline in U-wave Morphology
时间窗: Baseline up to Day 3
The percentage of participants with change from baseline with abnormal U-waves morphology that represent the appearance or worsening of the morphological abnormality will be reported.
次要结局
- Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])(Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose)
- Total Apparent Clearance (CL/F)(Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose)
- Apparent Volume of Distribution (Vd/F)(Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose)
- Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])(Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose)
- Elimination Half-Life (t1/2)(Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose)
- Metabolite to Parent (M/P) Ratio for AUC[infinity](Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose)
- Maximum Observed Plasma Concentration (Cmax)(Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose)
- Number of Participants with Adverse Events and Serious Edverse Events as a Measure of Safety and Tolerability(Approximately 11 weeks)
- Metabolite to Parent (M/P) Ratio for AUC[last](Pre-dose; 0.33, 0.5, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Post-dose)
- Relationship Between the Plasma Concentrations of Seltorexant and Changes in the QT/QTc Interval(Up to Day 3)