A Study to Investigate the Interaction Between JNJ-64155806 and Ethinylestradiol/Drospirenone in Healthy Females

• ClinicalTrials.gov Identifier: NCT03126097
• Recruitment Status: Terminated
• First Posted: April 24, 2017
• Last Update Posted: September 1, 2017
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief Summary:

The primary purpose of this study is to evaluate the effect of single and multiple doses of JNJ-64155806 on the steady-state pharmacokinetics (PK) of ethinylestradiol and drospirenone and vice versa in healthy female participants.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: JNJ-64155806 150 mg; Drug: Ethinylestradiol/drospirenone 0.02 mg/3 mg; Drug: COCP Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-label Study in Healthy Female Subjects to Investigate the Drug-drug Interaction Between JNJ-64155806 and Ethinylestradiol/Drospirenone
• Actual Study Start Date: April 13, 2017
• Actual Primary Completion Date: May 26, 2017
• Actual Study Completion Date: May 26, 2017

Arms and Interventions

Arm

Intervention/treatment

Experimental: JNJ-64155806+COCP+JNJ-64155806 with COCP; Participants will receive JNJ-64155806 150 milligram (mg) twice daily (BID) under fed conditions on Days 1 to 7 [JNJ-64155806 Alone Phase] followed by a 10-day washout phase; followed by Ethinylestradiol/drospirenone 0.02 mg/3 mg given as a combined oral contraceptive pill (COCP) once daily (QD) on Days 18 to 41 and COCP placebo QD on Days 42 to 45 [COCP Lead-in Phase]; further followed by COCP QD on Days 46 to 69 (on Days 59 to 66 under fed condition), JNJ‑64155806 150 mg BID (under fed conditions) on Days 60 to 66, and COCP placebo QD on Days 70 to 73 [JNJ-64155806 + COCP Co-administration Phase].

Drug: JNJ-64155806 150 mg; JNJ-64155806 150 mg (3*50 mg tablet) twice daily will be administered under fed conditions on Days 1 to 7 [JNJ-64155806 Alone Phase] and on Days 60 to 66 [JNJ-64155806 + COCP Coadministration Phase].; Drug: Ethinylestradiol/drospirenone 0.02 mg/3 mg; Each tablet contains 3 mg drospirenone and 0.02 mg ethinylestradiol administered as combined oral contraceptive pill (COCP) given on Days 18 to 41 (lead-in phase), Days 46 to 69 (coadministration phase - Days 59 to 66 under fed conditions).; Drug: COCP Placebo; Participant will receive COCP placebo tablets once daily on Days 42 to 45 (lead-in phase) and Days 70 to 73 (JNJ-64155806 + COCP coadministration phase).

Outcome Measures

Primary Outcome Measures :

1. Trough Plasma Concentration (Ctrough) for Ethinylestradiol [ Time Frame: Days 57, 58, 59, 60, 66 ]
   The Ctrough is the plasma concentration before dosing.
2. Trough Plasma Concentration (Ctrough) for Drospirenone [ Time Frame: Days 57, 58, 59, 60, 66 ]
   The Ctrough is the plasma concentration before dosing.
3. Minimum Observed Plasma Concentration (Cmin) for Ethinylestradiol [ Time Frame: Days 59, 60, 66: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours postdose ]
   The Cmin is the minimum observed plasma concentration.
4. Minimum Observed Plasma Concentration (Cmin) for Drospirenone [ Time Frame: Days 59, 60, 66: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours postdose ]
   The Cmin is the minimum observed plasma concentration.
5. Maximum Observed Plasma Concentration (Cmax) for Ethinylestradiol [ Time Frame: Days 59, 60, 66: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours postdose ]
   The Cmax is the maximum observed plasma concentration.
6. Maximum Observed Plasma Concentration (Cmax) for Drospirenone [ Time Frame: Days 59, 60, 66: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours postdose ]
   The Cmax is the maximum observed plasma concentration.
7. Time to Reach Maximum Observed Plasma Concentration (Tmax) for Ethinylestradiol [ Time Frame: Days 59, 60, 66: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours postdose ]
   The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
8. Time to Reach Maximum Observed Plasma Concentration (Tmax) for Drospirenone [ Time Frame: Days 59, 60, 66: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours postdose ]
   The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
9. Average Plasma Concentration (C24h) at 24hours for Ethinylestradiol [ Time Frame: Days 59, 60, 66 ]
   C24h is observed analyte concentration at 24 hours.
10. Average Plasma Concentration (C24h) at 24hours for Drospirenone [ Time Frame: Days 59, 60, 66 ]
    C24h is observed analyte concentration at 24 hours.
11. Average Plasma Concentration (Cavg) for Ethinylestradiol [ Time Frame: Days 59, 60, 66 ]
    Cavg is average analyte concentration at steady state, calculated as: AUC24h/24 hours at steady state [24 hours equal to (=) dosing interval].
12. Average Plasma Concentration (Cavg) for Drospirenone [ Time Frame: Days 59, 60, 66 ]
    Cavg is average analyte concentration at steady state, calculated as: AUC24h/24 hours at steady state [24 hours equal to (=) dosing interval].
13. Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24h]) for Ethinylestradiol [ Time Frame: Days 59, 60, 66 ]
    The AUC(0-24h) is the area under the plasma concentration time curve from time zero to 24 hours.
14. Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24h]) for Drospirenone [ Time Frame: Days 59, 60, 66 ]
    The AUC(0-24h) is the area under the plasma concentration time curve from time zero to 24 hours.
15. Fluctuation Index (FI) for Ethinylestradiol [ Time Frame: Days 59, 60, 66 ]
    FI is the percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax-Cmin]/Cavg).
16. Fluctuation Index (FI) for Drospirenone [ Time Frame: Days 59, 60, 66 ]
    FI is the percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax-Cmin]/Cavg).
17. Ratio of Cmin Values Between Test and Reference (Ratio Cmin,test/ref) for Ethinylestradiol [ Time Frame: Days 59, 60, 66 ]
    Ratio Cmin,test/ref is the ratio of individual Cmin values between test and reference treatment. Test is Day 60 (JNJ-64155806 single dose + ethinylestradiol/drospirenone) or Day 66 (JNJ-64155806 multiple dose + ethinylestradiol/drospirenone) and Reference is Day 59 (ethinylestradiol/drospirenone alone).
18. Ratio of Cmin Values Between Test and Reference (Ratio Cmin,test/ref) for Drospirenone [ Time Frame: Days 59, 60, 66 ]
    Ratio Cmin,test/ref is the ratio of individual Cmin values between test and reference treatment. Test is Day 60 (JNJ-64155806 single dose + ethinylestradiol/drospirenone) or Day 66 (JNJ-64155806 multiple dose + ethinylestradiol/drospirenone) and Reference is Day 59 (ethinylestradiol/drospirenone alone).
19. Ratio of Cmax Values Between Test and Reference Treatment (Ratio Cmax,test/ref) for Ethinylestradiol [ Time Frame: Days 59, 60, 66 ]
    Ratio Cmax,test/ref is the ratio of individual Cmax values between test and reference treatment. Test is Day 60 (JNJ-64155806 single dose + ethinylestradiol/drospirenone) or Day 66 (JNJ-64155806 multiple dose + ethinylestradiol/drospirenone) and Reference is Day 59 (ethinylestradiol/drospirenone alone).
20. Ratio of Cmax Values Between Test and Reference Treatment (Ratio Cmax,test/ref) for Drospirenone [ Time Frame: Days 59, 60, 66 ]
    Ratio Cmax,test/ref is the ratio of individual Cmax values between test and reference treatment. Test is Day 60 (JNJ-64155806 single dose + ethinylestradiol/drospirenone) or Day 66 (JNJ-64155806 multiple dose + ethinylestradiol/drospirenone) and Reference is Day 59 (ethinylestradiol/drospirenone alone).
21. Ratio of AUC(0-24h) Values Between Test and Reference (Ratio AUC[0-24h],test/ref) for Ethinylestradiol [ Time Frame: Days 59, 60, 66 ]
    Ratio AUC(0-24h),test/ref is the ratio of individual AUC(0-24h) values between test and reference treatment. Test is Day 60 (JNJ-64155806 single dose + ethinylestradiol/drospirenone) or Day 66 (JNJ-64155806 multiple dose + ethinylestradiol/drospirenone) and Reference is Day 59 (ethinylestradiol/drospirenone alone).
22. Ratio of AUC(0-24h) Values Between Test and Reference Treatment (Ratio AUC[0-24h],test/ref) for Drospirenone [ Time Frame: Days 59, 60, 66 ]
    Ratio AUC(0-24h),test/ref is the ratio of individual AUC(0-24h) values between test and reference treatment. Test is Day 60 (JNJ-64155806 single dose + ethinylestradiol/drospirenone) or Day 66 (JNJ-64155806 multiple dose + ethinylestradiol/drospirenone) and Reference is Day 59 (ethinylestradiol/drospirenone alone).

Secondary Outcome Measures :

1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From Signing of Informed Consent Form (ICF) till End of Study (Day 73) ]
   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. Minimum Observed Plasma Concentration (Cmin) for JNJ-64155806 [ Time Frame: Days 1, 7, 60, 66 ]
   The Cmin is the minimum observed plasma concentration.
3. Maximum Observed Plasma (Cmax) for JNJ-64155806 [ Time Frame: Days 1, 7, 60, 66 ]
   The Cmax is the maximum observed plasma concentration.
4. Time to Reach Maximum Observed Plasma Concentration (Tmax) for JNJ-64155806 [ Time Frame: Days 1, 7, 60, 66 ]
   The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
5. Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12h]) for JNJ-64155806 [ Time Frame: Days 1, 7, 60, 66 ]
   The AUC(0-12h) is the area under the plasma concentration time curve from time zero to 12 hours.
6. Area Under the Plasma Concentration-time Curve From 12 Hours to 24 Hours (AUC[12-24h]) for JNJ-64155806 [ Time Frame: Days 1, 7, 60, 66 ]
   The AUC(12h-24h) is the area under the plasma concentration time curve from time 12 hours to 24 hours.
7. Trough Plasma Concentration (Ctrough) for JNJ-64155806 [ Time Frame: Days 5, 6, 7, 64, 65, 66 ]
   Ctrough is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.
8. Average Analyte Concentration (Cavg) for JNJ-64155806 [ Time Frame: Days 7 and 66 ]
   Cavg is average analyte concentration at steady state, calculated as: AUC24h/24 hours at steady state [24 hours equal to (=) dosing interval].
9. Fluctuation Index (FI) for JNJ-64155806 [ Time Frame: Days 7 and 66 ]
   FI is the percentage fluctuation (variation between maximum and minimum concentration at steady state).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Participant must be female of childbearing potential with a normal menstrual cycle, not using oral contraceptives in the 30 days prior to screening
• Participant must have a body mass index (BMI; weight in kilogram (kg) divided by the square of height in meters [m]) of 18.0 to 30.0 kg/m^2, extremes included, and a body weight not less than (<) 50.0 kg
• Participant must be willing and able to adhere to the requirements, instructions, and prohibitions and restrictions specified in this protocol, and is likely to complete the study as planned
• Participant must be healthy on the basis of physical examination, medical history, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests performed at screening. If the results of the biochemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
• Participants must be willing to start ethinylestradiol/drospirenone contraception during the COCP lead-in and JNJ-64155806 + COCP coadministration phases

Exclusion Criteria:

• Participant is a woman who is pregnant as confirmed by a positive beta human chorionic gonadotropin (beta-hCG) laboratory test, or who was pregnant within 6 months prior to study start, or who is breast-feeding, or who is planning to become pregnant from signing of the informed consent form (ICF) until 90 days after the last dose of study drug
• Participant with creatinine clearance of less than (<) 90 milliliter per minute (mL/min) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation)
• Participant with a clinically significant cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic (syncope or seizures), thyroid, or any other medical illness or psychiatric disorder, as determined by the investigator and/or sponsor's medical monitor
• Participant has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being), or that could prevent, limit, or confound the protocol-specified assessments
• Participant with currently active gynecological disorders including, but not limited to, vaginal bleeding without an obvious reason and hyperprolactinemia with or without galactorrhea

Contacts and Locations

Locations

United States, Arizona

Celerion

Tempe, Arizona, United States, 85283

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT03126097 History of Changes
• Other Study ID Numbers: CR108266; 64155806FLZ1001 ( Other Identifier: Janssen Research & Development, LLC )
• First Posted: April 24, 2017
• Last Update Posted: September 1, 2017
• Last Verified: August 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Drospirenone; Drospirenone and ethinyl estradiol combination; Ethinyl Estradiol; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Mineralocorticoid Receptor Antagonists; Hormone Antagonists; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents; Reproductive Control Agents