Clinical trial NCT03058419: A Study to Evaluate the Effect of Oral Doses of JNJ-54175446 on the Inhibition of Cytochrome P450 CYP3A4, CYP2C9, CYP1A2 and CYP2D6 Activity and the Induction of CYP2B6 and CYP2C19 Activity Using a Multiple Probe Substrate Cocktail in Healthy Subjects
Official title: An Open-label Drug Interaction Study in Healthy Subjects to Evaluate the Effect of Oral Doses of JNJ-54175446 on the Inhibition of Cytochrome P450 CYP3A4, CYP2C9, CYP1A2 and CYP2D6 Activity and the Induction of CYP2B6 and CYP2C19 Activity Using a Multiple Probe Substrate Cocktail
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-02-20
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to determine the potential inhibitory/inducing effects of JNJ-54175446 after single and repeated dosing on the single-dose pharmacokinetics (PK) of a cocktail, containing selective probes of cytochrome P450 (CYP) enzymes (CYP3A4/A5, CYP2C9, CYP1A2, CYP2D6, CYP2B6, and CYP2C19) in healthy adult subjects.


Eligibility criteria: Inclusion Criteria:

* Subject must have a body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m\^2), inclusive (BMI = weight/height\^2)
* Subject must be healthy on the basis of physical examination, medical history, vital signs, and triplicate 12-lead electrocardiograms (ECGs), including QTc according to Fridericia's formula (QTcF) less than or equal to (\</=) 450 milliseconds (ms) for males and \</= 470 ms for females, performed at screening and first admission to the study site
* Subject must be healthy on the basis of clinical laboratory tests performed at screening and Day -1. If the results of the hematology, serology, serum chemistry (excluding liver function tests, which must be in normal range of 1.25 \* upper limit of normal laboratory range), and coagulation panel, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities to be not clinically significant
* During the study and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study drug, a male subject: Who is sexually active with a woman of childbearing potential and has not had vasectomy must agree to use a barrier method of contraception (eg, condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap \[diaphragm or cervical/vault caps\] with spermicidal foam/gel/film/cream/suppository). In addition, their female partner should also use a highly effective method of birth control (example, hormonal contraception) for at least the same duration. Who is sexually active with a woman who is pregnant must use a condom and Must agree not to donate sperm
* A female subject must be of non-childbearing potential at screening

Exclusion Criteria:

* Subject has a history of or current liver or renal insufficiency (estimated creatinine clearance below 60 milliliter per minute (mL/min), significant skin disease such as, but not limited to, dermatitis, eczema, Stevens-Johnson Syndrome, drug rash, psoriasis or urticaria, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic (including coagulation disorders), rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the investigator considers should exclude the subject
* Subject has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening
* Subject has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at screening
* Subject has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that, in the opinion of the investigator, with written concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence)
* Subject has a history of drug or alcohol use disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria within 6 months before screening

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Up to Day 17
measure: Plasma Trough Concentration (Ctrough)
timeFrame: Up to Day 17
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Up to Day 17
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last])
timeFrame: Up to Day 17
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
timeFrame: Up to Day 17
measure: Elimination Rate Constant (Lambda [z])
timeFrame: Up to Day 17
measure: Elimination Half-Life (t1/2)
timeFrame: Up to Day 17
measure: Apparent Total Clearance (CL/F)
timeFrame: Up to Day 17
measure: Apparent Volume of Distribution (Vd/F)
timeFrame: Up to Day 17
measure: Parent to Metabolite Ratio (Cmax)
timeFrame: Up to Day 17
measure: Parent to Metabolite Ratio (AUC [Last])
timeFrame: Up to Day 17
measure: Parent to Metabolite Ratio (AUC [infinity])
timeFrame: Up to Day 17
Secondary outcomes:
measure: Number of Subjects With Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to follow up (14 to 21 days after last dose)
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical trial
role: STUDY_DIRECTOR
References: