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)

A Phase 1, Open-label Study in Healthy Female Subjects 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)

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Drospirenone/Ethinylestradiol; Drug: Midazolam; Drug: JNJ-56136379

• Study Type: Interventional
• Enrollment (Actual): 18
• 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 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Drospirenone/Ethinylestradiol + Midazolam + JNJ-56136379; 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; A single dose of drospirenone/ethinylestradiol 3 mg/0.02 mg (OC) tablets on Days 1 and 21.; Other Names: Betadex clathrate (Yaz); Drug: Midazolam; Midazolam 2 mg orally on Days 1 and 21.; Drug: JNJ-56136379; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events 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.	Up to 30-35 days after last study drug administration (approximately 70 days)
Maximum Observed Plasma Concentration of JNJ-56136379 (Cmax)	The Cmax is the maximum observed plasma analyte concentration.	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)	AUCtau is area under concentration-time curve from time 0 to tau hours postdose, calculated by linear-linear trapezoidal summation.	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	Steady-state plasma concentration of JNJ-56136379 will be evaluated after multiple dosing.	Days 16, 19, 20 and 21 (predose)

Collaborators and Investigators

• Sponsor: Janssen Sciences Ireland UC

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2017
• Primary Completion (Actual): August 23, 2017
• Study Completion (Actual): August 23, 2017

Study Registration Dates

• First Submitted: March 20, 2017
• First Submitted That Met QC Criteria: April 7, 2017
• First Posted (Actual): April 12, 2017

Study Record Updates

• Last Update Posted (Actual): September 6, 2017
• Last Update Submitted That Met QC Criteria: September 1, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Antiviral Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Natriuretic Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Diuretics; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Sequestering Agents; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Midazolam; Ethinyl Estradiol; JNJ-56136379; Betadex; Drospirenone; Drospirenone and ethinyl estradiol combination
• Other Study ID Numbers: CR108309; 56136379HPB1004 (Other Identifier: Janssen Sciences Ireland UC); 2017-000365-70 (EudraCT Number)

Drug and device information, study documents

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