Clinical trial NCT03547024: A Study in Healthy Participants to Evaluate the Effects of Multiple Doses of JNJ-55308942 on Cytochrome P450 Substrate Activity and on the Pharmacokinetics of Levonorgestrel/Ethinyl Estradiol
Official title: An Open-Label Drug Interaction Study in Healthy Subjects to Evaluate the Effects of Multiple Doses of JNJ55308942 on the Cytochrome P450 CYP3A4, CYP2D6 and CYP2C19 Activity and on the Pharmacokinetics of Levonorgestrel/Ethinyl Estradiol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2018-06-06
Enrollment: 14
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: OTHER

Brief summary: The purpose of this study is to determine the effect of JNJ-55308942: 1) high dose at steady state on the single dose pharmacokinetics of a cocktail containing selective probes of cytochrome P450 (CYP) enzymes (CYP3A, CYP2D6 and CYP2C19) in healthy adult participants (Part 1); 2) high dose at steady state on the single dose pharmacokinetics of a combination oral contraceptive containing levonorgestrel and ethinyl estradiol in healthy female participants (Part 2); and 3) low dose at steady state on the single dose pharmacokinetics of a cocktail containing selective probes of CYP enzymes (CYP3A, CYP2D6 and CYP2C19) in healthy adult participants (Part 3).


Eligibility criteria: Inclusion Criteria:

* A body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m\^2), inclusive (BMI = weight/height\^2)
* Healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and first admission (Day -1) to the clinical unit. Minor abnormalities in ECG, which are not considered to be of clinical significance by the physician investigator, are acceptable
* Healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel \[excluding liver function tests\], hematology \[including coagulation\], or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the participant's source documents and initialed/signed by the physician investigator
* All women of child-bearing potential must have a negative highly sensitive serum (beta human chorionic gonadotropin \[beta hCG\]) at screening and a negative urine pregnancy test on Day -1
* A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 1 month after the last study drug administration

Exclusion Criteria:

* History of or current liver or renal insufficiency; 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 participant
* History of or current positive testing for hepatitis B surface antigen (HBsAg), Hepatitis B core (HBcAb) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening
* History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at screening
* 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)
* History of at least drug or alcohol use disorder according to Diagnostic and Statistical Manual of Mental Disorders (latest edition DSM-5) criteria within 6 months before screening

Primary outcomes:
measure: Parts 1 and 3: Maximum Observed Analyte Concentration (Cmax) of Each Probe Substrate in Cocktail
timeFrame: Predose, 15 minute (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h on Days 1 and 12
measure: Parts 1 and 3: Area Under the Analyte Concentration-Time Curve from Time Zero to the Time of the Last Measurable Concentration (AUC[0-last]) of Each Probe Substrate in Cocktail
timeFrame: Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h on Days 1 and 12
measure: Parts 1 and 3: Area Under the Analyte Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Each Probe Substrate in Cocktail
timeFrame: Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h on Days 1 and 12
measure: Part 2: Cmax of Levonorgestrel and Ethinyl Estradiol
timeFrame: Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h on Days 1 and 14
measure: Part 2: AUC(0-last) of Levonorgestrel and Ethinyl Estradiol
timeFrame: Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h on Days 1 and 14
measure: Part 2: AUC(0-infinity) of Levonorgestrel and Ethinyl Estradiol
timeFrame: Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h on Days 1 and 14
Secondary outcomes:
measure: Parts 1, 2 and 3: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Approximately 10 weeks
measure: Parts 1, 2 and 3: Observed Analyte Concentration Just Prior to the Beginning or at the end of a Dosing Interval (Ctrough) of JNJ-55308942
timeFrame: Predose on Days 4 to 11, predose, up to 72 hours postdose on Day 12 (Parts 1 and 3); Predose on Days 5 to 13, predose, up to 120 hour postdose on Day 14 (Part 2)
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References: