A Randomized, Placebo- and Comparator-controlled, Double-blind, Multiple (Ascending) Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-54175446 in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 76
- 主要终点
- Number of Participants with Adverse Events
研究概览
简要总结
The purpose of this study is to investigate the safety, tolerability and pharmacodynamics of JNJ-54175446 after multiple consecutive dose administrations
详细描述
This will be a randomized, placebo-and comparator-controlled, double-blind, multiple dose study with JNJ-54175446 in healthy male participants. The study will consist of a Screening examination (28 to 6 days prior to dose administration), a baseline 20 mg amphetamine (AMPH) challenge at least 5 days before first dose administration, a double-blind treatment period (18 days; 11 days of dosing with JNJ-54175446, minocycline or placebo; amphetamine (AMPH)/AMPH placebo challenge sequence on Day 7 and Day 10 for each participant), and a follow-up examination between 14 and 21 days after last dose administration. The maximal study duration for each participant will not exceed 9 weeks. Safety, pharmacokinetics (PK) and pharmacodynamics of JNJ-54175446 will be primarily assessed. 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
- Double (Participant, Investigator)
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
- •Participant must have a body mass index (BMI) between 18 and 32 kilogram/meter^2 (kg/m^2), inclusive (BMI = weight/height^2)
- •Participants must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) [including QTcF less than or equal to 450 millisecond (ms) (triplicate ECG)] performed at screening and admission to the clinical unit. Minor abnormalities in ECG, which are not considered to be of clinical significance by the investigator, are acceptable. The presence of Left Bundle Branch Block (LBBB), atrioventricular (AV) Block (second degree or higher), or a permanent pacemaker or implantable cardioverter defibrillator [ICD] will lead to exclusion
- •Participants must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel [including liver enzymes], hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the investigator
- •A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug. In addition, their female partner should also use an appropriate method of birth control for at least the same duration
排除标准
- •Participant has a history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the Investigator considers should exclude the subject
- •Participant has a clinically significant (history of) psychiatric illnesses or (history of) psychotic symptoms
- •Participant has a family history of relevant psychiatric disorders (first degree) and/or psychotic disorders (first and second degree)
- •Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening
- •Participant has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening
研究组 & 干预措施
Cohort 1
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ-54175446 (Drug)
Cohort 1
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: Minocycline (Drug)
Cohort 1
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ 54175446 Matching Placebo (Drug)
Cohort 1
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine (Drug)
Cohort 1
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine Matching Placebo (Drug)
Cohort 2
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ-54175446 (Drug)
Cohort 2
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: Minocycline (Drug)
Cohort 2
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ 54175446 Matching Placebo (Drug)
Cohort 2
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine (Drug)
Cohort 2
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine Matching Placebo (Drug)
Cohort 3
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ-54175446 (Drug)
Cohort 3
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: Minocycline (Drug)
Cohort 3
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ 54175446 Matching Placebo (Drug)
Cohort 3
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine (Drug)
Cohort 3
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine Matching Placebo (Drug)
Cohort 4
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ-54175446 (Drug)
Cohort 4
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: Minocycline (Drug)
Cohort 4
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ 54175446 Matching Placebo (Drug)
Cohort 4
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine (Drug)
Cohort 4
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine Matching Placebo (Drug)
Cohort 5
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ-54175446 (Drug)
Cohort 5
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: Minocycline (Drug)
Cohort 5
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ 54175446 Matching Placebo (Drug)
Cohort 5
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine (Drug)
Cohort 5
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine Matching Placebo (Drug)
Cohort 6
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ-54175446 (Drug)
Cohort 6
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: Minocycline (Drug)
Cohort 6
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ 54175446 Matching Placebo (Drug)
Cohort 6
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine (Drug)
Cohort 6
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine Matching Placebo (Drug)
Cohort 7
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ-54175446 (Drug)
Cohort 7
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ 54175446 Matching Placebo (Drug)
Cohort 7
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine (Drug)
Cohort 7
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine Matching Placebo (Drug)
Cohort 8
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ-54175446 (Drug)
Cohort 8
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: JNJ 54175446 Matching Placebo (Drug)
Cohort 8
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine (Drug)
Cohort 8
Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17.
干预措施: D Amphetamine Matching Placebo (Drug)
结局指标
主要结局
Number of Participants with Adverse Events
时间窗: Baseline up to 14 or 21 days after study drug administration
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Maximum Observed Plasma Concentration (Cmax)
时间窗: Baseline up to Day 17
The Cmax is the maximum observed concentration.
Minimum Observed Plasma Concentration (Cmin)
时间窗: Baseline up to Day 17
The Cmin is the minimum observed plasma concentration.
Trough Plasma Concentration (Ctrough)
时间窗: Baseline up to Day 17
The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.
Average Plasma Concentration at Steady State (Cavg,ss)
时间窗: Baseline up to Day 17
The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC\[tau\]) divided by the dosing interval (tau).
Time to Reach Maximum Observed Plasma Concentration (Tmax)
时间窗: Baseline up to Day 17
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t])
时间窗: Baseline up to Day 17
The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
时间窗: Baseline up to Day 17
The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
Elimination Half-Life (t1/2)
时间窗: Baseline up to Day 17
The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
次要结局
未报告次要终点