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

Janssen (J&J Innovative Medicine)

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: Omeprazole 20 mg

Drug: JNJ-54175446 150 mg

Drug: Caffeine 50 mg

Drug: Warfarin 10 mg

Drug: Midazolam 2 mg

Drug: JNJ-54175446 600 mg

Drug: Dextromethorphan 30 mg

Drug: Bupropion 150 mg

Study type

Interventional

Funder types

Industry

Identifiers

NCT03058419

CR108283

54175446EDI1006 (Other Identifier)

2016-004167-39 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment

16 patients

Sex

All

Ages

18 to 60 years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

16 participants in 1 patient group

Drug Cocktail + JNJ-54175446

Experimental group

Description:

All subjects will receive a single dose of drug cocktail (consisting of midazolam \[2 milligram (mg)\], warfarin \[10 mg\], caffeine \[50 mg\], dextromethorphan \[30 mg\], bupropion \[150 mg\] and omeprazole \[20 mg\]) on Day 1, 7 and 11; JNJ-54175446 150 mg on Day 7, 9, 10 and 11 and JNJ-54175446 600 mg on Day 8.

Treatment: