An Open-Label, Randomized, Parallel-Group Drug-Drug Interaction Study to Assess the Effect of Multiple Doses of Itraconazole or Gemfibrozil on the Pharmacokinetics of a Single Dose of JNJ-56021927 in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 主要终点
- Maximum Plasma Concentration (Cmax)
研究概览
简要总结
The purpose of this study is to assess the effect of multiple doses of itraconazole or gemfibrozil on the pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time) of JNJ-56021927 and its metabolites (JNJ 56142060 and JNJ-56142021) in healthy male participants.
详细描述
This is a single-dose, single-center, open-label (all people know the identity of the intervention), 3-treatment, randomized (study medication assigned to participants by chance) and parallel-group (a medical research study comparing the response in two or more groups of participants receiving different interventions [treatments]) study. The study consists of Screening Phase (that is, 21 days before study commences on Day 1); open-label treatment Phase and end-of-study or early withdrawal assessment. All participants will be randomly assigned to 1 of 3 treatments, that is, Treatment A (single dose of JNJ-56021927 on Day 1), Treatment B (200 milligram [mg] itraconazole once daily from Day 1 up to Day 32 along with single dose of JNJ-56021927 on Day 4), and Treatment C (600 mg gemfibrozil twice daily from Day 1 up to Day 32 along with single dose of JNJ-56021927 on Day 4). Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. The maximum duration of participation in the study per participant will be approximately 78 days (Treatment A) or 81 days (Treatment B and C). Participants' safety will be monitored throughout the study.
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
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Must agree to use an adequate contraception method as deemed appropriate by the Investigator and specified in protocol, always use a condom during sexual intercourse, and to not donate sperm during the study and for 3 months after receiving the study drug
- •Body mass index between 18 and 30 kilogram (kg) per square meter, and body weight not less than 50 kg
- •Blood pressure (supine for 5 minutes) between 90 and 140 millimeter of mercury (mm Hg) systolic, and no higher than 90 mm Hg diastolic
- •A 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function at Screening, including: Pulse rate between 45 and 99 beats per minute (bpm); QTc interval less than or equal to (<=) 450 milliseconds; QRS interval of less than (<) 120 milliseconds; PR interval <220 milliseconds; and morphology consistent with healthy cardiac conduction and function
- •Nonsmoker within the previous 2 months (calculated from first dosing)
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, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the Investigator considers should exclude the participant or that could interfere with the interpretation of the study results
- •Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at Screening or at admission to the study center as deemed appropriate by the Investigator
- •Medical history of gallbladder disease (cholecystitis, cholelithiasis, cholecystectomy)
- •Presence of sexual dysfunction or any medical condition that would affect sexual function
- •Screening serum testosterone level of < 200 nanogram/deciliter (ng/dL)
- •Previous history of photoallergy or phototoxic reaction during treatment with fibrates
研究组 & 干预措施
Treatment A
Single oral dose of JNJ-56021927 240 milligram (mg) capsule will be administered on Day 1.
干预措施: JNJ-56021927 (Drug)
Treatment B
Itraconazole 200 mg (2 capsules of 100 mg) will be administered once daily orally from Day 1 until Day 32, along with single oral dose of JNJ-56021927 240 mg capsule on Day 4.
干预措施: JNJ-56021927 (Drug)
Treatment B
Itraconazole 200 mg (2 capsules of 100 mg) will be administered once daily orally from Day 1 until Day 32, along with single oral dose of JNJ-56021927 240 mg capsule on Day 4.
干预措施: Itraconazole (Drug)
Treatment C
Gemfibrozil 600 mg oral tablet will be administered twice daily from Day 1 until Day 32, along with single oral dose of JNJ-56021927 240 mg capsule on Day 4.
干预措施: JNJ-56021927 (Drug)
Treatment C
Gemfibrozil 600 mg oral tablet will be administered twice daily from Day 1 until Day 32, along with single oral dose of JNJ-56021927 240 mg capsule on Day 4.
干预措施: Gemfibrozil (Drug)
结局指标
主要结局
Maximum Plasma Concentration (Cmax)
时间窗: Up to Day 57 or Day 60
The Cmax is the maximum observed plasma concentration. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
Time to Reach Maximum Concentration (tmax)
时间窗: Up to Day 57 or Day 60
The tmax is time to reach the maximum observed plasma concentration. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
Metabolite to Parent Drug Ratio for maximum observed plasma concentration (MPR Cmax)
时间窗: Up to Day 57 or Day 60
Metabolite to parent drug ratio for maximum observed plasma concentration will be calculated. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
Metabolite to Parent Drug Ratio for AUC (0-infinity) (MPR AUC [0-infinity])
时间窗: Up to Day 57 or Day 60
Metabolite to parent drug ratio for AUC (0-infinity) will be calculated. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
Total Plasma Clearance (CL/F) of JNJ-56021927
时间窗: Up to Day 57 or Day 60
Total plasma clearance of drug after extravascular administration, uncorrected for absolute bioavailability, calculated as Dose/AUC (0-infinity) (JNJ-56021927 only). Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
Area Under the Plasma Concentration-Time Curve From Time Zero to 672 Hours (AUC [0-672])
时间窗: Up to Day 57 or Day 60
The AUC (0-672) is the area under the plasma concentration-time curve from time zero to 672 hours. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
时间窗: Up to Day 57 or Day 60
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
时间窗: Up to Day 57 or Day 60
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
Percentage of Extrapolated AUC (0-infinity)
时间窗: Up to Day 57 or Day 60
The percentage of AUC (0-infinity) that is due to extrapolation from Tlast to infinity (AUC%Extrapolation) is calculated by using the formula AUC_%extrapolation = 100\*(AUC \[0-infinity\] minus (AUC \[0-last\])/(AUC (0-infinity). Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
Elimination Half-Life (t [1/2] Lambda)
时间窗: Up to Day 57 or Day 60
Elimination half-life (t \[1/2\] Lambda) is associated with the terminal slope (lambda \[z\]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z). Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
Rate Constant (Lambda[z])
时间窗: Up to Day 57 or Day 60
Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
Time to last quantifiable plasma concentration (tlast)
时间窗: Up to Day 57 or Day 60
The tlast is the time to last observed quantifiable plasma concentration. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
Metabolite to Parent Drug Ratio for AUC (0 to last) (MPR AUC [0-last])
时间窗: Up to Day 57 or Day 60
Metabolite to parent drug ratio for AUC (0 to last) will be calculated. Blood samples will be collected up to Day 57 (for Treatment A) or Day 60 (for Treatment B and C).
次要结局
- Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)(Screening up to Day 57 for treatment A or up to Day 60 for treatment B or C or early withdrawal)