A Study to Assess the Effects of Itraconazole and Rifampicin on the Single-Dose Pharmacokinetics of JNJ-53718678 in Healthy Adults

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-53718678; Drug: Itraconazole; Drug: Rifampicin

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel 1; Participants will receive a single 250 milligram (mg) dose of JNJ-53718678 on Day 1 and 200 mg itraconazole once a day on Days 4 to 11 along with a single 250-mg dose of JNJ-53718678 on Day 9.	Drug: JNJ-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).; Drug: Itraconazole; Participants will receive itraconazole 200 mg (2 capsules of 100 mg) from Day 4-11.
Experimental: Panel 2; Participants will receive a single 500-mg dose of JNJ-53718678 on Day 1; a single 600-mg dose of rifampicin along with a single 500-mg dose of JNJ-53718678 on Day 4 and 600 mg rifampicin once daily on Days 5 to 11 along with a single 500-mg dose of JNJ-53718678 on Day 9.	Drug: JNJ-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).; Drug: Rifampicin; Participants will receive 600 mg rifampicin (2 capsules of 300 mg) from Day 4-11.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Analyte Concentration (Cmax)	The Cmax is the maximum observed analyte concentration after the JNJ-53718678 doses on Day 1, Day 4 (Panel 2 only) and Day 9.	Up to 11 days
Area Under the Analyte Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC [0-last])	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.	Up to 11 days
Area Under the Analyte Concentration-Time Curve From Time 0 to Infinite Time (AUC [0-infinity])	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.	Up to 11 days
Area Under the Analyte Concentration-time curve From Time 0 to 24h (AUC24h)	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).	Up to 11 days
Ratio of Individual Cmax Values Between Test and Reference Treatment (Ratio Cmax, test/reference)	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.	Up to 11 days
Ratio of Individual AUC24h Values Between Test and Reference Treatment (Ratio AUC24h, test/reference)	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.	Up to 11 days
Ratio of Individual AUClast Values Between Test and Reference Treatment (Ratio AUClast, test/reference)	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.	Up to 11 days
Ratio of Individual AUC(infinity) Values Between Test and Reference Treatment (Ratio AUC[infinity], test/reference)	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.	Up to 11 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events and Serious Adverse Events	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.	Screening up to Follow-up (30 to 35 days after last study drug intake)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: March 18, 2016
• First Submitted That Met QC Criteria: March 31, 2016
• First Posted (Estimated): April 6, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Healthy; Pharmacokinetics; Itraconazole; JNJ-53718678; Rifampicin
• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Antibiotics, Antitubercular; Antitubercular Agents; Cytochrome P-450 CYP3A Inhibitors; Leprostatic Agents; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inducers; 14-alpha Demethylase Inhibitors; Rifampin; Itraconazole
• Other Study ID Numbers: CR108127; 53718678RSV1006 (Other Identifier: Janssen Research & Development, LLC)