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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Drug Cocktail:Midazolam (2mg)/Omeprazole (20mg)/Dextromethorphan (30mg); Drug: JNJ-55308942 High Dose; Drug: JNJ-55308942 Low Dose; Drug: Levonorgestrel/Ethinyl Estradiol Fixed Dose combination (FDC)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03547024

55308942EDI1003 (Other Identifier)

2018-000194-75 (EudraCT Number)

CR108486

Details and patient eligibility

About

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).

Enrollment: 14 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

14 participants in 3 patient groups

Part 1: JNJ-55308942 + Drug Cocktail

Experimental group

Description:

Participants will receive a single dose of drug cocktail on Day 1 followed by JNJ-55308942 high dose once daily from Day 3 to Day 14 and a single dose of drug cocktail on Day 12.

Treatment:

Drug: JNJ-55308942 High Dose

Drug: Drug Cocktail:Midazolam (2mg)/Omeprazole (20mg)/Dextromethorphan (30mg)

Part 2: JNJ-55308942 + Levonorgestrel/Ethinyl Estradiol

Experimental group

Description:

Participants will receive a single dose of levonorgestrel/ethinyl estradiol alone on Day 1 followed by JNJ-55308942 high dose once daily on Days 5 to 18 and a single dose of levonorgestrel/ethinyl estradiol on Day 14.

Treatment:

Drug: Levonorgestrel/Ethinyl Estradiol Fixed Dose combination (FDC)

Drug: JNJ-55308942 High Dose

Drug: Drug Cocktail:Midazolam (2mg)/Omeprazole (20mg)/Dextromethorphan (30mg)

Part 3: JNJ-55308942 + Drug Cocktail

Experimental group

Description:

Participants will receive a single dose of drug cocktail alone on Day 1 followed by JNJ-55308942 low dose once daily on Days 3 to Day 14 and a single dose drug cocktail on Day 12.

Treatment:

Drug: JNJ-55308942 Low Dose

Drug: Drug Cocktail:Midazolam (2mg)/Omeprazole (20mg)/Dextromethorphan (30mg)