Clinical trial NCT02729467: A Study to Assess the Effects of Itraconazole and Rifampicin on the Single-Dose Pharmacokinetics of JNJ-53718678 in Healthy Adults
Official title: An Open-Label Fixed-Sequence Study to Assess the Effects of Itraconazole and Rifampicin on the Single-Dose Pharmacokinetics of JNJ-53718678 in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
JNJ-53718678
Itraconazole
Rifampicin
Pharmacokinetics
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-04-06
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effects of itraconazole, a strong cytochrome P (CYP)3A4 and p-glycoprotein (PgP) inhibitor, and rifampicin, a CYP3A4, uridine 5'-diphospho-glucuronosyltransferase (UGT), and PgP inducer, and an inhibitor of organic anion-transporting polypeptide (OATP), on the single-dose pharmacokinetics (PK) of JNJ-53718678 in healthy adult participants.

Detailed description: This is a single-center, open-label, fixed sequence, Phase 1 study in healthy adult participants to study the effects of itraconazole and rifampicin on the pharmacokinetics, safety, and tolerability of a single dose of JNJ-53718678. This study will be conducted in 2 separate panels, with 14 participants in Panel 1 and 16 participants in Panel 2. The study consists of following phases: Screening (28 days), Treatment phase (11 days) and Follow-up (10 to 14 days after the last study drug intake). Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. Participants will be assessed for safety and tolerability throughout the study.

Eligibility criteria: Inclusion Criteria:

* Female participants must have a negative serum beta human chorionic gonadotropin (beta hCG) pregnancy test at Screening
* At Screening, a female participant must be of non-childbearing potential
* Participant must have a Body Mass Index (BMI; weight in kilogram (kg) divided by the square of height in meters) of 18.0 to 30.0 kilogram per meter square (kg/m2), extremes included
* Participant must have a blood pressure (after the participant is supine for 5 minutes) between 90 and 140 millimeters of mercury (mmHg) systolic, inclusive, and not higher than 90 mm Hg diastolic
* Participants must be healthy on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination (including height and body weight measurement and skin examination), medical history, vital signs, and the results of blood biochemistry, blood coagulation, and hematology tests, and a urinalysis performed at Screening

Exclusion Criteria:

* Participant with a history of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders, lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic insufficiency, renal dysfunction, 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
* Participants with abnormal values for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (greater than \[\>\]1.00 \* upper limit of laboratory normal range \[ULN\])
* Participants with lack of good/reasonable venous access
* Participants with a past history of heart arrhythmias (extrasystoli, tachycardia at rest) or, history of risk factors for Torsade de Pointes syndrome (example - hypokalemia, family history of long QT Syndrome)
* Participants with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, and urticaria

Primary outcomes:
measure: Maximum Observed Analyte Concentration (Cmax)
timeFrame: Up to 11 days
measure: Area Under the Analyte Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC [0-last])
timeFrame: Up to 11 days
measure: Area Under the Analyte Concentration-Time Curve From Time 0 to Infinite Time (AUC [0-infinity])
timeFrame: Up to 11 days
measure: Area Under the Analyte Concentration-time curve From Time 0 to 24h (AUC24h)
timeFrame: Up to 11 days
measure: Ratio of Individual Cmax Values Between Test and Reference Treatment (Ratio Cmax, test/reference)
timeFrame: Up to 11 days
measure: Ratio of Individual AUC24h Values Between Test and Reference Treatment (Ratio AUC24h, test/reference)
timeFrame: Up to 11 days
measure: Ratio of Individual AUClast Values Between Test and Reference Treatment (Ratio AUClast, test/reference)
timeFrame: Up to 11 days
measure: Ratio of Individual AUC(infinity) Values Between Test and Reference Treatment (Ratio AUC[infinity], test/reference)
timeFrame: Up to 11 days
Secondary outcomes:
measure: Number of Participants With Adverse Events and Serious Adverse Events
timeFrame: Screening up to Follow-up (30 to 35 days after last study drug intake)
Other outcomes:
Locations:
city: Overland Park
country: United States
state: Kansas
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: