Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 100 for:    DROSPIRENONE AND ETHINYL ESTRADIOL

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03111511
Recruitment Status : Completed
First Posted : April 12, 2017
Last Update Posted : September 6, 2017
Sponsor:
Information provided by (Responsible Party):
Janssen Sciences Ireland UC

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Drospirenone/Ethinylestradiol Drug: Midazolam Drug: JNJ-56136379 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: 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)
Actual Study Start Date : March 27, 2017
Actual Primary Completion Date : August 23, 2017
Actual Study Completion Date : August 23, 2017

Resource links provided by the National Library of Medicine


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 Name: 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.




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration of Drospirenone (Cmax) [ Time Frame: 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.

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

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

  4. Maximum Observed Plasma Concentration of Ethinylestradiol (Cmax) [ Time Frame: 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.

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

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

  7. Maximum Observed Plasma Concentration of Midazolam and its Metabolite 1-OH-Midazolam (Cmax) [ Time Frame: 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.

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

  9. 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]) [ Time Frame: 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.


Secondary Outcome Measures :
  1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 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.

  2. Maximum Observed Plasma Concentration of JNJ-56136379 (Cmax) [ Time Frame: 1, 2, 4, 9 and 12 hours postdose on Day 21 ]
    The Cmax is the maximum observed plasma analyte concentration.

  3. Area Under the Concentration-time Curve From Time Zero to tau Hours Postdose of JNJ-56136379 (AUCtau) [ Time Frame: 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.

  4. Steady-state Plasma Concentration of JNJ-56136379 After Multiple Dosing [ Time Frame: Days 16, 19, 20 and 21 (predose) ]
    Steady-state plasma concentration of JNJ-56136379 will be evaluated after multiple dosing.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03111511


Locations
Layout table for location information
Belgium
Clinical Pharmacology Unit
Merksem, Belgium, 2170
Sponsors and Collaborators
Janssen Sciences Ireland UC
Investigators
Layout table for investigator information
Study Director: Janssen Sciences Ireland UC Clinical Trial Janssen Sciences Ireland UC

Layout table for additonal information
Responsible Party: Janssen Sciences Ireland UC
ClinicalTrials.gov Identifier: NCT03111511     History of Changes
Other Study ID Numbers: CR108309
56136379HPB1004 ( Other Identifier: Janssen Sciences Ireland UC )
2017-000365-70 ( EudraCT Number )
First Posted: April 12, 2017    Key Record Dates
Last Update Posted: September 6, 2017
Last Verified: September 2017

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Ethinyl Estradiol
Drospirenone
Drospirenone and ethinyl estradiol combination
Midazolam
Contraceptive Agents
Contraceptives, Oral
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Reproductive Control Agents
Contraceptive Agents, Female
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents