Clinical trial NCT02230033: Study to Assess Drug-Drug Interaction Between Itraconazole or Gemfibrozil and JNJ-56021927
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: JNJ-56021927
Itraconazole
Gemfibrozil
Lead sponsor: Aragon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-09-03
Enrollment: 45
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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)

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, 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

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax)
timeFrame: Up to Day 57 or Day 60
measure: Time to Reach Maximum Concentration (tmax)
timeFrame: Up to Day 57 or Day 60
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to 672 Hours (AUC [0-672])
timeFrame: Up to Day 57 or Day 60
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
timeFrame: Up to Day 57 or Day 60
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
timeFrame: Up to Day 57 or Day 60
measure: Percentage of Extrapolated AUC (0-infinity)
timeFrame: Up to Day 57 or Day 60
measure: Elimination Half-Life (t [1/2] Lambda)
timeFrame: Up to Day 57 or Day 60
measure: Rate Constant (Lambda[z])
timeFrame: Up to Day 57 or Day 60
measure: Time to last quantifiable plasma concentration (tlast)
timeFrame: Up to Day 57 or Day 60
measure: Total Plasma Clearance (CL/F) of JNJ-56021927
timeFrame: Up to Day 57 or Day 60
measure: Metabolite to Parent Drug Ratio for maximum observed plasma concentration (MPR Cmax)
timeFrame: Up to Day 57 or Day 60
measure: Metabolite to Parent Drug Ratio for AUC (0 to last) (MPR AUC [0-last])
timeFrame: Up to Day 57 or Day 60
measure: Metabolite to Parent Drug Ratio for AUC (0-infinity) (MPR AUC [0-infinity])
timeFrame: Up to Day 57 or Day 60
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Screening up to Day 57 for treatment A or up to Day 60 for treatment B or C or early withdrawal
Other outcomes:
Locations:
city: Tempe
country: United States
state: Arizona
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: