An Open-Label, Randomized, Multi-panel, Crossover Study to Evaluate the Relative Oral Bioavailability and Food Effect of Seltorexant (JNJ-42847922) After Single-Dose Administration in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 151
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-Time Curve Extrapolated to Infinite Time (AUC[0-infinity])
研究概览
简要总结
The purpose of this study is to compare the rate and extent of absorption (relative bioavailability) of seltorexant Phase 3 test formulation(s) relative to a reference Phase 2b tablet formulation dosed in the evening under fasted and semi-fasted conditions (3 hours after meal); to assess the effect of type and timing of the meal on the rate and extent of absorption of seltorexant Phase 3 tablet formulation (low dose and high dose strength) in healthy male and female participants; and to assess the pharmacokinetic of single-dose administration of low dose and high dose of seltorexant in healthy male and female participants 3 hours after meal.
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
- None
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
- •Be healthy on the basis of medical history (screening only), physical examination, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and Day 1 (predose)
- •Be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
- •All female participants (regardless of childbearing potential), must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening and a negative urine pregnancy test on Day -1 of each treatment period
- •A woman 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 man, 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 (for example, abstinence, vasectomy, barrier method, partner using effective contraception)
排除标准
- •History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic (Child-Pugh Score greater than or equal to [>=] 7) or renal insufficiency (estimated glomerular filtration rate [eGFR] less than [<] 60 milliliter per minute per 1.73 meter square [mL/min/1.73m^2] based on the modified diet renal disease [MDRD] formula at screening only), thyroid disease, neurologic (including seizure disorders) or psychiatric disease (depression or anxiety disorder in remission is acceptable), infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results. Significant past gastrointestinal medical history, or any disease/surgery that would with interfere drug absorption
- •Clinically significant abnormal values for hematology, clinical chemistry (including thyroid stimulating hormone [TSH] at screening only) or urinalysis at screening or at admission to the study site. It is expected that laboratory values will generally be within the normal range for the laboratory, though minor deviations, which are not considered to be of clinical significance to the investigator, are acceptable
- •Clinically significant abnormal physical examination, vital signs, or 12-lead ECG at screening or at admission to the study site though minor deviations, which are not considered to be of clinical significance to the investigator are acceptable
- •Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for acetaminophen, oral contraceptives, and hormonal replacement therapy within 14 days before the first dose of the study drug is scheduled. Or has used any systemic herbal medications or dietary supplements including products containing Hypericum perforatum (for example, St. John's Wort) from 21 days before the first dose of study drug is scheduled
- •Received a known inhibitor of Cytochrome P450 3A4 (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
研究组 & 干预措施
Part 1: Seltorexant High Dose
In Part 1, participants will receive the following treatments: Treatment A: Two low doses of seltorexant tablets (reference formulation), Treatment B: High dose of seltorexant tablet (Test formulation 1), Treatment C: High dose of seltorexant tablet (Test formulation 2), Treatment D: Two low doses of seltorexant tablets (Test formulation 3), Treatment E: Two low doses of seltorexant tablets (Test formulation 4), Treatment F: Two low doses of seltorexant tablets (Test formulation 5), as one of 6 possible treatment sequences on Day 1 in each treatment Periods (Period 1-6). There will be a washout Period of 7 to 14 days from dosing on Day 1 of each treatment period.
干预措施: Seltorexant High Dose (Drug)
Part 2: Seltorexant High Dose
Participants will receive the following treatments: Treatment G: Two low doses of seltorexant tablets (Reference formulation), Treatment H: High dose or two low doses of seltorexant tablet (Test formulation 1), Treatment I: High dose of seltorexant tablet (Test formulation 2), as one of 6 possible treatment sequences on Day 1 in each treatment Periods (Period 1-3). There will be a washout period of 7 to 14 days from dosing on Day 1 of each treatment period.
干预措施: Seltorexant High Dose (Drug)
Part 3: Seltorexant Low Dose or High Dose
Part 3 will have 3 subparts (Part 3A, Part 3B, and Part 3C). In Part 3A and 3B, participants will receive high dose of seltorexant (selected formulation 6) and two low doses of seltorexant (selected formulation 7) respectively in a different food conditions on Day 1 in each treatment Periods (Periods 1-5). In Part 3C, participants will receive high dose of seltorexant (selected formulation 6) and two low doses of seltorexant (selected formulation 7 ) on Day 1 in each period (Period 1 and 2). There will be a washout period of 7 to 14 days from dosing on Day 1 of each treatment period.
干预措施: Seltorexant High Dose (Drug)
Part 3: Seltorexant Low Dose or High Dose
Part 3 will have 3 subparts (Part 3A, Part 3B, and Part 3C). In Part 3A and 3B, participants will receive high dose of seltorexant (selected formulation 6) and two low doses of seltorexant (selected formulation 7) respectively in a different food conditions on Day 1 in each treatment Periods (Periods 1-5). In Part 3C, participants will receive high dose of seltorexant (selected formulation 6) and two low doses of seltorexant (selected formulation 7 ) on Day 1 in each period (Period 1 and 2). There will be a washout period of 7 to 14 days from dosing on Day 1 of each treatment period.
干预措施: Seltorexant Low Dose (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve Extrapolated to Infinite Time (AUC[0-infinity])
时间窗: Predose, up to 48 hours postdose
AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated using the observed value of the last non-zero plasma concentration.
Maximum Observed Plasma Concentration (Cmax)
时间窗: Predose up to 48 hours postdose
Cmax is the maximum observed plasma concentration.
Area Under the Plasma Concentration-Time Curve from the Time of Dosing to the Last Measurable Plasma Concentration (AUC[0-last])
时间窗: Predose up to 48 hours postdose
AUC(0-last) is the area under the plasma concentration-time curve from the time of dosing to the last measurable plasma concentration.
次要结局
- Dose-Proportionality of Seltorexant Based on AUC(0-last)(Predose up to 48 hours postdose)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(Part 1: approximately 16 weeks; Part 2: approximately 10 weeks; Part 3: approximately 39 weeks)
- Dose-Proportionality of Seltorexant Based on Cmax(Predose up to 48 hours postdose)
- Change from Baseline in Karolinska Sleepiness Scale (KSS) Score(Baseline, Day 1, and Day 2)
- Dose-Proportionality of Seltorexant Based on AUC(0-infinity)(Predose up to 48 hours postdose)
- Plasma Protein Binding (PPB) of Seltorexant and Its Metabolites (M12 and M16)(Predose up to 12 hours postdose)