A Study in Healthy Female Participants to Investigate the Effect of JNJ-56136379 at Steady-state on the Single-dose Pharmacokinetics of Ethinylestradiol and Drospirenone (Oral Contraceptive) and on the Single-dose Pharmacokinetics of Midazolam (Probe Substrate for Cytochrome P450 3A4)

NCT03111511 | Completed Phase 1

• 3 other identifiers: CR10830956136379HPB10042017-000365-70
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to evaluate the effect of steady-state concentrations of JNJ-56136379 on the single-dose pharmacokinetics (PK) of drospirenone and ethinylestradiol (oral contraceptive \[OC\]) in healthy female participants and to evaluate the effect of steady-state concentrations of JNJ-56136379 on the single-dose PK of midazolam (sensitive probe substrate for CYP3A4) in healthy female participants.

Conditions

Healthy

Outcome Measures

Primary Outcomes (9)

• Maximum Observed Plasma Concentration of Drospirenone (Cmax)

  The Cmax is the maximum observed plasma analyte concentration.

  Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose

• Area Under the Analyte Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration of Drospirenone (AUC [0-last])

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

  Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose

• Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time of Drospirenone (AUC [0-infinity])

  The AUC (0-infinity) is the area under the plasma 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 plasma 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.

  Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose

• Maximum Observed Plasma Concentration of Ethinylestradiol (Cmax)

  The Cmax is the maximum observed plasma analyte concentration.

  Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose

• Area Under the Analyte Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration of Ethinylestradiol (AUC [0-last])

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

  Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose

• Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time of Ethinylestradiol (AUC [0-infinity])

  The 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.

  Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose

• Maximum Observed Plasma Concentration of Midazolam and its Metabolite 1-OH-Midazolam (Cmax)

  The Cmax is the maximum observed plasma analyte concentration.

  Day 1 and 21: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose on Day 1

• Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time of Midazolam and its Metabolite 1-OH-Midazolam (AUC [0-infinity])

  The 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.

  Day 1 and 21: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose

• Area Under the Analyte Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration of Midazolam and its Metabolite 1-OH-Midazolam (AUC [0-last])

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

  Day 1 and 21: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose

Secondary Outcomes (4)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  Up to 30-35 days after last study drug administration (approximately 70 days)

• Maximum Observed Plasma Concentration of JNJ-56136379 (Cmax)

  1, 2, 4, 9 and 12 hours postdose on Day 21

• Area Under the Concentration-time Curve From Time Zero to tau Hours Postdose of JNJ-56136379 (AUCtau)

  Predose, 1, 2, 4, 9 and 12 hours postdose on Day 21; predose on Day 22

• Steady-state Plasma Concentration of JNJ-56136379 After Multiple Dosing

  Days 16, 19, 20 and 21 (predose)

Study Arms (1)

Drospirenone/Ethinylestradiol + Midazolam + JNJ-56136379

EXPERIMENTAL

Participants will receive single dose of drospirenone/ethinylestradiol 3 milligram (mg)/0.02 mg (oral contraceptive \[OC\]) and single dose of midazolam 2 mg under fasted conditions on Day 1. JNJ-56136379 250 mg twice daily will be administered on Days 6, 7 and JNJ-56136379 170 mg once daily on Days 8 to 25 under fed conditions, except on Day 21 on which Single dose of JNJ-56136379 170 mg + single dose of OC and single dose of midazolam 2 mg will be administered on fasted state. A single dose of drospirenone/ethinylestradiol 3 mg/0.02 mg and midazolam 2 mg on Day 21 under fasted conditions.

Drug: Drospirenone/Ethinylestradiol; Drug: Midazolam; Drug: JNJ-56136379

Interventions

Drospirenone/Ethinylestradiol DRUG

A single dose of drospirenone/ethinylestradiol 3 mg/0.02 mg (OC) tablets on Days 1 and 21.

Also known as: Betadex clathrate (Yaz)

Drospirenone/Ethinylestradiol + Midazolam + JNJ-56136379

Midazolam DRUG

Midazolam 2 mg orally on Days 1 and 21.

Drospirenone/Ethinylestradiol + Midazolam + JNJ-56136379

JNJ-56136379 DRUG

JNJ-56136379 dose will be administered orally at a dose of 250 mg (as 2 tablets of 100 mg + 2 tablets of 25 mg) on Days 6 and 7 and at a dose of 170 mg (as 1 tablet of 100 mg+ 2 tablets of 25 mg + 4 tablets of 5 mg) on Days 8 to 25.

Drospirenone/Ethinylestradiol + Midazolam + JNJ-56136379

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy on the basis of physical examination, medical history, and vital signs performed at screening. If there are abnormalities, the participant may be included only if the investigator judges the abnormalities to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator
• healthy on the basis of clinical laboratory tests performed at screening
• must have a normal 12-lead electrocardiogram (ECG) at screening including: normal sinus rhythm (heart rate between 45 and 100 beats per minute \[bpm\], extremes included); QT interval corrected for heart rate (QTc) according to Fridericia (QTcF) less than equal to (\<=)470 milliseconds (ms); QRS interval less than (\<)120 ms; PR interval \<=220 ms
• must have a blood pressure (after the participant is supine for 5 minutes) between 90 and 140 millimeters of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic. If blood pressure is out of range, up to 2 repeated assessments are permitted
• must have a body mass index (BMI; weight in kg divided by the square of height in meters) between 18.0 and 30.0 kilogram per square meter (kg/m\^2), extremes included, and a body weight not less than 50.0 kilogram (kg)

You may not qualify if:

• any evidence of heart block or bundle branch block
• history of liver or renal dysfunction (estimated creatinine clearance \<60 milliliters per minute (mL/min) at screening, calculated by the Modification of Diet in Renal Disease \[MDRD\] formula12), significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances
• past history of cardiac arrhythmias (example \[eg\], extrasystoli, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family history of long QT Syndrome)
• current human immunodeficiency virus type 1 (HIV-1) or HIV-2 infection (confirmed by antibodies) at screening
• any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, and urticaria

Sponsors & Collaborators

• Janssen Sciences Ireland UC: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

MeSH Terms

Interventions

drospirenone; Ethinyl Estradiol; drospirenone and ethinyl estradiol combination; Midazolam; JNJ-56136379

Intervention Hierarchy (Ancestors)

Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Janssen Sciences Ireland UC Clinical Trial

  Janssen Sciences Ireland UC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2017
• First Posted: April 12, 2017
• Study Start: March 27, 2017
• Primary Completion: August 23, 2017
• Study Completion: August 23, 2017
• Last Updated: September 6, 2017

Record last verified: 2017-09

Locations

BE (1)