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

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

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).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-55308942 High Dose; Drug: Drug Cocktail:Midazolam (2mg)/Omeprazole (20mg)/Dextromethorphan (30mg); Drug: Levonorgestrel/Ethinyl Estradiol Fixed Dose combination (FDC); Drug: JNJ-55308942 Low Dose

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium, 2170
    • Clinical Pharmacology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: JNJ-55308942 + Drug Cocktail; 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; Participants will receive high dose of JNJ-55308942 orally once daily.; Drug: Drug Cocktail:Midazolam (2mg)/Omeprazole (20mg)/Dextromethorphan (30mg); Participants will receive single dose of drug cocktail consisting of midazolam (2 mg), dextromethorphan (30mg) and omeprazole (20 mg) orally.
Experimental: Part 2: JNJ-55308942 + Levonorgestrel/Ethinyl Estradiol; 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; Participants will receive high dose of JNJ-55308942 orally once daily.; Drug: Drug Cocktail:Midazolam (2mg)/Omeprazole (20mg)/Dextromethorphan (30mg); Participants will receive single dose of drug cocktail consisting of midazolam (2 mg), dextromethorphan (30mg) and omeprazole (20 mg) orally.; Drug: Levonorgestrel/Ethinyl Estradiol Fixed Dose combination (FDC); Participants will receive 0.150 milligram (mg) levonorgestrel and 0.030 mg ethinyl estradiol FDC tablet orally.; Other Names: Microgynon 30
Experimental: Part 3: JNJ-55308942 + Drug Cocktail; 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: Drug Cocktail:Midazolam (2mg)/Omeprazole (20mg)/Dextromethorphan (30mg); Participants will receive single dose of drug cocktail consisting of midazolam (2 mg), dextromethorphan (30mg) and omeprazole (20 mg) orally.; Drug: JNJ-55308942 Low Dose; Participants will receive low dose of JNJ-55308942 orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts 1, 2 and 3: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	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	Ctrough is the observed analyte concentration just prior to the beginning or at the end of a dosing interval in a multiple dosing regimen.	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)

Collaborators and Investigators

• Sponsor: Janssen-Cilag International NV

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2018
• Primary Completion (Actual): August 30, 2018
• Study Completion (Actual): August 30, 2018

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (Actual): June 6, 2018

Study Record Updates

• Last Update Posted (Actual): October 1, 2018
• Last Update Submitted That Met QC Criteria: September 27, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Respiratory System Agents; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Anti-Ulcer Agents; Proton Pump Inhibitors; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Antitussive Agents; Purinergic P2X Receptor Antagonists; Midazolam; Levonorgestrel; Estradiol; Ethinyl Estradiol; Dextromethorphan; Omeprazole; Ethinyl estradiol, levonorgestrel drug combination; JNJ-55308942
• Other Study ID Numbers: CR108486; 2018-000194-75 (EudraCT Number); 55308942EDI1003 (Other Identifier: Janssen-Cilag International NV)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No