Clinical trial NCT02692677: A Study to Assess the Absorption, Metabolism, and Routes of Excretion Following Oral Administration of (14C) Radiolabeled JNJ--42756493 to Healthy Male Participants
Official title: An Open-Label Phase 1 Study to Determine the Absorption, Metabolism, and Routes of Excretion Following Oral Administration of (14C) Radiolabeled JNJ-42756493 to Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
JNJ-42756493
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-02-26
Enrollment: 8
Sex: MALE
Minimum age (years): 30
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to assess the absorption, metabolism, and excretion of JNJ-42756493 in healthy male adult participants after administration of a single oral dose of 12 milligram (mg) of unlabeled JNJ-42756493 admixed with 14C JNJ-42756493.

Detailed description: This is a single--center, open--label (The researchers and participants know the treatment the participant is receiving) study. The study consists of 3 parts: Screening (35 days ), Open-label Treatment Phase (Day 1 up to Day 14 or 28); and Follow-up (up to 30 days). Total duration of the study is approximately 79 to 93 days. Plasma and urine will be collected for determination of JNJ-42756493 concentrations. Participants will be primarily evaluated for absorption, the metabolic pathways and the excretion of JNJ-42756493. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Willing to adhere to the prohibitions and restrictions specified in the protocol
* A man who is sexually active must agree to use a condom; and a man who is sexually active with a woman of childbearing potential and has not had a vasectomy, must agree to use a condom in combination with an adequate contraception method as deemed appropriate by the investigator (example, double-barrier method, partner using effective contraception \[defined as hormonal contraception (pill, patch, injection), intrauterine device, surgical sterilization\] and to not donate sperm for 5 months after receiving the study drug
* Body mass index (BMI; weight \[kg\]/height2 \[m\]2) between 18 and 30 kilogram per square meter (kg/m2) (inclusive), and body weight not less than 50 kg

Exclusion Criteria:

* 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 or renal insufficiency \[creatinine clearance below 90 milliliter per minute (mL/min)\], 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
* History or current evidence of ophthalmic disorder, such as central serous retinopathy or retinal vein occlusion, active wet age related macular degeneration, diabetic retinopathy with macular edema, uncontrolled glaucoma, corneal pathology such as keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation or ulceration
* Clinically significant abnormal physical examination, vital signs, or 12 lead electrocardiogram (ECG) and clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or at screening or at admission to the study center as deemed appropriate by the investigator
* Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for acetaminophen, within 14 days before dosing is scheduled until End-of-Study procedures
* History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV) criteria within 5 years before screening or positive test result(s) for alcohol and/or drugs of abuse (such as barbiturates, opiates, cocaine, cannabinoids, amphetamines, and benzodiazepines) at screening and Day -2 of the treatment period.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Apparent Clearance (CL/F)
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Apparent Volume of Distribution (Vd/F)
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Elimination Rate Constant
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Unbound Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Unbound Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Amount of Drug Excreted in Urine (Ae)
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Renal Clearance (CLR)
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Area Under First Moment Plasma Concentration-Time Curve (AUMC)
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Elimination Half-Life Associated With the Terminal Slope
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Percentage of Drug Excreted in Urine (Ae%dose)
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Amount of Drug Excreted in Urine (Ae) from t1 to t2
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
measure: Percentage of Extrapolated Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (Percentage AUCinfinity, extrapolated [%AUCinf,ex])
timeFrame: Pre-dose,0.5,1,2,3,4,8,12 hour post-dose(pd) on Day 1;24,36 h pd on Day 2;48 h pd on Day 3,72 h pd on Day 4; 96 h pd on Day 5;192 h pd on Day 9,216 h pd on Day 10,240 h pd on Day 11,264 h pd on Day 12,288 h pd on Day 13 and 312 h pd on Day 14
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Baseline up to follow up (79 to 93 days)
Other outcomes:
Locations:
city: Madison
country: United States
state: Wisconsin
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: