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

NCT03547024 | Completed Phase 1

• 3 other identifiers: CR1084862018-000194-7555308942EDI1003
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy

Outcome Measures

Primary Outcomes (6)

• Parts 1 and 3: Maximum Observed Analyte Concentration (Cmax) of Each Probe Substrate in Cocktail

  Cmax of probe substrates in cocktail containing selective probes of CYP enzymes (CYP3A, CYP2D6 and CYP2C19) will be determined.

  Predose, 15 minute (min), 30min, 45min, 1 hour (h), 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h on Days 1 and 12

• 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

  AUC(0-last) of probe substrates in cocktail containing selective probes of CYP enzymes (CYP3A, CYP2D6 and CYP2C19) will be determined.

  Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h on Days 1 and 12

• 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

  AUC (0-infinity) of probe substrates in cocktail containing selective probes of CYP enzymes (CYP3A, CYP2D6 and CYP2C19) will be determined.

  Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h on Days 1 and 12

• Part 2: Cmax of Levonorgestrel and Ethinyl Estradiol

  Cmax is the maximum observed analyte concentration.

  Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h on Days 1 and 14

• Part 2: AUC(0-last) of Levonorgestrel and Ethinyl Estradiol

  AUC(0-last) is defined as the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentration.

  Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h on Days 1 and 14

• Part 2: AUC(0-infinity) of Levonorgestrel and Ethinyl Estradiol

  AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the analyte concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.

  Predose, 15min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 18h on Days 1 and 14

Secondary Outcomes (2)

• Parts 1, 2 and 3: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability

  Approximately 10 weeks

• 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

  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)

Study Arms (3)

Part 1: JNJ-55308942 + Drug Cocktail

EXPERIMENTAL

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.

Drug: JNJ-55308942 High Dose; Drug: Drug Cocktail:Midazolam (2mg)/Omeprazole (20mg)/Dextromethorphan (30mg)

Part 2: JNJ-55308942 + Levonorgestrel/Ethinyl Estradiol

EXPERIMENTAL

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.

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

Part 3: JNJ-55308942 + Drug Cocktail

EXPERIMENTAL

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.

Drug: JNJ-55308942 Low Dose; Drug: Drug Cocktail:Midazolam (2mg)/Omeprazole (20mg)/Dextromethorphan (30mg)

Interventions

JNJ-55308942 High Dose DRUG

Participants will receive high dose of JNJ-55308942 orally once daily.

Part 1: JNJ-55308942 + Drug Cocktail; Part 2: JNJ-55308942 + Levonorgestrel/Ethinyl Estradiol

JNJ-55308942 Low Dose DRUG

Participants will receive low dose of JNJ-55308942 orally once daily.

Part 3: JNJ-55308942 + Drug Cocktail

Levonorgestrel/Ethinyl Estradiol Fixed Dose combination (FDC) DRUG

Participants will receive 0.150 milligram (mg) levonorgestrel and 0.030 mg ethinyl estradiol FDC tablet orally.

Also known as: Microgynon 30

Part 2: JNJ-55308942 + Levonorgestrel/Ethinyl Estradiol

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

Participants will receive single dose of drug cocktail consisting of midazolam (2 mg), dextromethorphan (30mg) and omeprazole (20 mg) orally.

Part 1: JNJ-55308942 + Drug Cocktail; Part 2: JNJ-55308942 + Levonorgestrel/Ethinyl Estradiol; Part 3: JNJ-55308942 + Drug Cocktail

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen-Cilag International NV: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

MeSH Terms

Interventions

JNJ-55308942; Levonorgestrel; Ethinyl Estradiol; Omeprazole; Dextromethorphan

Intervention Hierarchy (Ancestors)

Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Norpregnatrienes; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons

Study Officials

• Janssen-Cilag International NV Clinical Trial

  Janssen-Cilag International NV

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: June 6, 2018
• Study Start: June 8, 2018
• Primary Completion: August 30, 2018
• Study Completion: August 30, 2018
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

BE (1)