Healthy
Conditions
Keywords
Healthy, JNJ-53718678, Itraconazole, Rifampicin, Pharmacokinetics
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.
Interventions
DRUGJNJ-53718678
JNJ-53718678 will be applied twice at doses of 250 mg (in Panel 1, Day 1 and Day 9) and 3 times at 500 mg (Panel 2, Day 1, 4 and 9).
DRUGItraconazole
Participants will receive itraconazole 200 mg (2 capsules of 100 mg) from Day 4-11.
DRUGRifampicin
Participants will receive 600 mg rifampicin (2 capsules of 300 mg) from Day 4-11.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of Individual AUC(infinity) Values Between Test and Reference Treatment (Ratio AUC[infinity], test/reference) | Up to 11 days | Ratio AUC(infinity), test/reference is the ratio of individual AUC(infinity) values between test (JNJ-53718678 with itraconazole or rifampicin, on Day 9) and reference (without itraconazole or rifampicin, on Day 1) treatments. |
| Maximum Observed Analyte Concentration (Cmax) | Up to 11 days | The Cmax is the maximum observed analyte concentration after the JNJ-53718678 doses on Day 1, Day 4 (Panel 2 only) and Day 9. |
| Area Under the Analyte Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC [0-last]) | Up to 11 days | The (AUC \[0-last\]) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentration after the JNJ-53718678 doses on Day 1 and Day 9. |
| Area Under the Analyte Concentration-Time Curve From Time 0 to Infinite Time (AUC [0-infinity]) | Up to 11 days | The AUC (0-infinity) is the area under the Analyte concentration-time curve from time 0 to infinite time after the JNJ-53718678 doses on Day 1 and Day 9, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z), wherein AUC(0-last) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentrations; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant. |
| Area Under the Analyte Concentration-time curve From Time 0 to 24h (AUC24h) | Up to 11 days | The AUC24h is the area under the analyte concentration-time curve from time 0 to 24h after dosing on Day 1 and Day 4 (Panel 2 only). |
| Ratio of Individual Cmax Values Between Test and Reference Treatment (Ratio Cmax, test/reference) | Up to 11 days | Ratio Cmax, test/reference is the ratio of individual Cmax values between test (JNJ-53718678 with itraconazole, on Day 9, or JNJ-53718678 with rifampicin, on Day 4 and Day 9) and reference (without itraconazole or rifampicin, on Day 1) treatments. |
| Ratio of Individual AUC24h Values Between Test and Reference Treatment (Ratio AUC24h, test/reference) | Up to 11 days | Ratio AUC24h, test/reference is the ratio of individual AUC24h values between test (JNJ-53718678 with rifampicin, on Day 4) and reference (without rifampicin, on Day 1) treatments. |
| Ratio of Individual AUClast Values Between Test and Reference Treatment (Ratio AUClast, test/reference) | Up to 11 days | Ratio AUClast, test/reference is the ratio of individual AUClast values between test (JNJ-53718678 with itraconazole or rifampicin, on Day 9) and reference (without itraconazole or rifampicin, on Day 1) treatments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events and Serious Adverse Events | Screening up to Follow-up (30 to 35 days after last study drug intake) | 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. |
Countries
United States
Outcome results
None listed