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

NCT03126097 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CR10826664155806FLZ1001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (22)

• Trough Plasma Concentration (Ctrough) for Ethinylestradiol

  The Ctrough is the plasma concentration before dosing.

  Days 57, 58, 59, 60, 66

• Trough Plasma Concentration (Ctrough) for Drospirenone

  The Ctrough is the plasma concentration before dosing.

  Days 57, 58, 59, 60, 66

• Minimum Observed Plasma Concentration (Cmin) for Ethinylestradiol

  The Cmin is the minimum observed plasma concentration.

  Days 59, 60, 66: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours postdose

• Minimum Observed Plasma Concentration (Cmin) for Drospirenone

  The Cmin is the minimum observed plasma concentration.

  Days 59, 60, 66: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours postdose

• Maximum Observed Plasma Concentration (Cmax) for Ethinylestradiol

  The Cmax is the maximum observed plasma concentration.

  Days 59, 60, 66: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours postdose

• Maximum Observed Plasma Concentration (Cmax) for Drospirenone

  The Cmax is the maximum observed plasma concentration.

  Days 59, 60, 66: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours postdose

• Time to Reach Maximum Observed Plasma Concentration (Tmax) for Ethinylestradiol

  The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

  Days 59, 60, 66: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours postdose

• Time to Reach Maximum Observed Plasma Concentration (Tmax) for Drospirenone

  The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

  Days 59, 60, 66: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours postdose

• Average Plasma Concentration (C24h) at 24hours for Ethinylestradiol

  C24h is observed analyte concentration at 24 hours.

  Days 59, 60, 66

• Average Plasma Concentration (C24h) at 24hours for Drospirenone

  C24h is observed analyte concentration at 24 hours.

  Days 59, 60, 66

• Average Plasma Concentration (Cavg) for Ethinylestradiol

  Cavg is average analyte concentration at steady state, calculated as: AUC24h/24 hours at steady state \[24 hours equal to (=) dosing interval\].

  Days 59, 60, 66

• Average Plasma Concentration (Cavg) for Drospirenone

  Cavg is average analyte concentration at steady state, calculated as: AUC24h/24 hours at steady state \[24 hours equal to (=) dosing interval\].

  Days 59, 60, 66

• Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24h]) for Ethinylestradiol

  The AUC(0-24h) is the area under the plasma concentration time curve from time zero to 24 hours.

  Days 59, 60, 66

• Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24h]) for Drospirenone

  The AUC(0-24h) is the area under the plasma concentration time curve from time zero to 24 hours.

  Days 59, 60, 66

• Fluctuation Index (FI) for Ethinylestradiol

  FI is the percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100\*(\[Cmax-Cmin\]/Cavg).

  Days 59, 60, 66

• Fluctuation Index (FI) for Drospirenone

  FI is the percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100\*(\[Cmax-Cmin\]/Cavg).

  Days 59, 60, 66

• Ratio of Cmin Values Between Test and Reference (Ratio Cmin,test/ref) for Ethinylestradiol

  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).

  Days 59, 60, 66

• Ratio of Cmin Values Between Test and Reference (Ratio Cmin,test/ref) for Drospirenone

  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).

  Days 59, 60, 66

• Ratio of Cmax Values Between Test and Reference Treatment (Ratio Cmax,test/ref) for Ethinylestradiol

  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).

  Days 59, 60, 66

• Ratio of Cmax Values Between Test and Reference Treatment (Ratio Cmax,test/ref) for Drospirenone

  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).

  Days 59, 60, 66

• Ratio of AUC(0-24h) Values Between Test and Reference (Ratio AUC[0-24h],test/ref) for Ethinylestradiol

  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).

  Days 59, 60, 66

• Ratio of AUC(0-24h) Values Between Test and Reference Treatment (Ratio AUC[0-24h],test/ref) for Drospirenone

  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).

  Days 59, 60, 66

Secondary Outcomes (9)

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

  From Signing of Informed Consent Form (ICF) till End of Study (Day 73)

• Minimum Observed Plasma Concentration (Cmin) for JNJ-64155806

  Days 1, 7, 60, 66

• Maximum Observed Plasma (Cmax) for JNJ-64155806

  Days 1, 7, 60, 66

• Time to Reach Maximum Observed Plasma Concentration (Tmax) for JNJ-64155806

  Days 1, 7, 60, 66

• Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC[0-12h]) for JNJ-64155806

  Days 1, 7, 60, 66

Study Arms (1)

JNJ-64155806+COCP+JNJ-64155806 with COCP

EXPERIMENTAL

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; Drug: Ethinylestradiol/drospirenone 0.02 mg/3 mg; Drug: COCP Placebo

Interventions

JNJ-64155806 150 mg DRUG

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 \[JNJ-64155806 + COCP Coadministration Phase\].

JNJ-64155806+COCP+JNJ-64155806 with COCP

Ethinylestradiol/drospirenone 0.02 mg/3 mg DRUG

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).

JNJ-64155806+COCP+JNJ-64155806 with COCP

COCP Placebo DRUG

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).

JNJ-64155806+COCP+JNJ-64155806 with COCP

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Ethinyl Estradiol; drospirenone

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

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 13, 2017
• First Posted: April 24, 2017
• Study Start: April 13, 2017
• Primary Completion: May 26, 2017
• Study Completion: May 26, 2017
• Last Updated: September 1, 2017

Record last verified: 2017-08

Locations

US (1)