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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03547024
• Other study ID #: CR108486
• Secondary ID: 2018-000194-7555
• Status: Completed
• Phase: Phase 1
• Start date: June 8, 2018
• Est. completion date: August 30, 2018

Study information

• Verified date: September 2018
• Source: Janssen-Cilag International NV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: August 30, 2018
• Est. primary completion date: August 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-55308942 High Dose
Participants will receive high dose of JNJ-55308942 orally once daily.
• JNJ-55308942 Low Dose
Participants will receive low dose of JNJ-55308942 orally once daily.
• Levonorgestrel/Ethinyl Estradiol Fixed Dose combination (FDC)
Participants will receive 0.150 milligram (mg) levonorgestrel and 0.030 mg ethinyl estradiol FDC tablet orally.
• 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.

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology Unit	Merksem

Sponsors (1)

Lead Sponsor	Collaborator
Janssen-Cilag International NV

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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)