Healthy
Conditions
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.
Interventions
A single dose of drospirenone/ethinylestradiol 3 mg/0.02 mg (OC) tablets on Days 1 and 21.
DRUGMidazolam
Midazolam 2 mg orally on Days 1 and 21.
DRUGJNJ-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.
Sponsors
Janssen Sciences Ireland UC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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]) | Day 1 and 21: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose | The AUC (0-last) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentration. |
| Area Under the Analyte Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration of Ethinylestradiol (AUC [0-last]) | Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose | The AUC (0-last) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentration. |
| Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time of Ethinylestradiol (AUC [0-infinity]) | Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose | 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. |
| Maximum Observed Plasma Concentration of Midazolam and its Metabolite 1-OH-Midazolam (Cmax) | Day 1 and 21: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose on Day 1 | The Cmax is the maximum observed plasma analyte concentration. |
| Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time of Midazolam and its Metabolite 1-OH-Midazolam (AUC [0-infinity]) | Day 1 and 21: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose | 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. |
| Maximum Observed Plasma Concentration of Drospirenone (Cmax) | Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose | The Cmax is the maximum observed plasma analyte concentration. |
| Area Under the Analyte Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration of Drospirenone (AUC [0-last]) | Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose | The AUC (0-last) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentration. |
| Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time of Drospirenone (AUC [0-infinity]) | Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose | 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. |
| Maximum Observed Plasma Concentration of Ethinylestradiol (Cmax) | Day 1 and 21: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours postdose | The Cmax is the maximum observed plasma analyte concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration of JNJ-56136379 (Cmax) | 1, 2, 4, 9 and 12 hours postdose on Day 21 | The Cmax is the maximum observed plasma analyte concentration. |
| 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 | AUCtau is area under concentration-time curve from time 0 to tau hours postdose, calculated by linear-linear trapezoidal summation. |
| Steady-state Plasma Concentration of JNJ-56136379 After Multiple Dosing | Days 16, 19, 20 and 21 (predose) | Steady-state plasma concentration of JNJ-56136379 will be evaluated after multiple dosing. |
| 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) | 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. |
Countries
Belgium
Outcome results
None listed