Clinical trial NCT02652650: A Study to Investigate the Effect of JNJ-63623872 at Steady-state on the Steady-state Pharmacokinetics of Ethinylestradiol and Norethindrone
Official title: A Phase 1, Open-label Study in Healthy Female Subjects to Investigate the Effect of JNJ-63623872 at Steady-state on the Steady-state Pharmacokinetics of Ethinylestradiol and Norethindrone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
JNJ-63623872
Ethinylestradiol
Norethindrone
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-01-12
Enrollment: 18
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The purpose of this study is to evaluate the effect of steady-state concentrations of JNJ-63623872 on the steady-state pharmacokinetics of ethinylestradiol and norethindrone in healthy female participants.

Detailed description: This is a Phase 1 and open-label study. The study consists of Screening Phase (less than or equal to (\<=) 28 days before Day 1), Treatment Phase (Day 1 up to Day 78) and Follow up Phase (10 to 14 days after last study drug intake or, if an adverse event occurs, 30 to 35 days after last study drug intake). Treatment phase will consist of three Oral Contraceptive (OC) cycles (each cycle consists of 21 days of ethinylestradiol/norethindrone followed by 7 pill-free days). The duration of the treatment phase, including the OC-free period of Cycles I and II, will be 78 days. Blood samples will be collected for measurement of pharmacokinetic (Pk) parameters. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Participant must be willing and able to adhere to the prohibitions and restrictions specified in the protocol
* Participants must, if heterosexually active with a partner who is not vasectomized (confirmed sterile), be practicing an effective method of contraception before entry and agree to continue to use two effective methods of contraception throughout the study and for at least 30 days after receiving the last intake of oral contraceptive (OC) plus JNJ-63623872 on Day 77
* Participants must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 of Cycle I
* Participants must agree not to donate eggs (ova, oocytes) during the study and for at least 90 days after receiving the last intake of OC plus JNJ-63623872 on Day 77
* Participants must have a Body Mass Index (BMI); between 18.0 and 30.0 kilogram per square meter (kg/m\^2) (extremes included)

Exclusion Criteria:

* Participant has a history of current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the Investigator considers should exclude the participant or that could interfere with the interpretation of the study results
* At screening, participants with one or more of the laboratory abnormalities specified in the protocol as defined by the World Health Organization (WHO) Toxicity Grading Scale
* Participant with a past history of heart arrhythmias (extrasystole, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (example, hypokalemia, family history of long QT Syndrome)
* Participants with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticarial
* Participants with a history of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy diagnosed in previous studies with experimental drugs

Primary outcomes:
measure: Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of JNJ-63623872
timeFrame: Post-dose on Days 75 and 76 of Cycle III
measure: Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of JNJ-63623872
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II
measure: Observed Analyte Concentration at 12 Hours Post Dosing (C12h) of JNJ-63623872
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II
measure: Minimum Observed Analyte Concentration (Cmin) of JNJ-63623872
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II
measure: Maximum Observed Analyte Concentration (Cmax) of JNJ-63623872
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II
measure: Time To Reach The Maximum Observed Analyte Concentration (Tmax) of JNJ-63623872
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II
measure: Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 12 Hours Post Dosing (AUC12h) of JNJ-63623872
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II
measure: Average Steady-State Plasma Concentration (Cavg) of JNJ-63623872
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II
measure: Percentage Fluctuation (FI) of JNJ-63623872
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II
measure: Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of Ethinylestradiol
timeFrame: Post-dose on Days 47 and 48 of Cycle II; post-dose on Days 75 and 76 of Cycle III
measure: Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of Norethindrone
timeFrame: Post-dose on Days 47 and 48 of Cycle II; post-dose on Days 75 and 76 of Cycle III
measure: Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of Ethinylestradiol
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of Norethindrone
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Observed Analyte Concentration at 24 Hours Post Dosing (C24h) of Ethinylestradiol
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Observed Analyte Concentration at 24 Hours Post Dosing (C24h) of Norethindrone
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Minimum Observed Analyte Concentration (Cmin) of Ethinylestradiol
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Minimum Observed Analyte Concentration (Cmin) of Norethindrone
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Maximum Observed Analyte Concentration (Cmax) of Ethinylestradiol
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Maximum Observed Analyte Concentration (Cmax) of Norethindrone
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Time To Reach The Maximum Observed Analyte Concentration (Tmax) of Ethinylestradiol
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Time To Reach The Maximum Observed Analyte Concentration (Tmax) of Norethindrone
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Area Under the Analyte Concentration versus Time Curve (auc) From Time of Administration up to 24 Hours Post Dosing (AUC24h) of Ethinylestradiol
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Area Under the Analyte Concentration versus Time Curve (auc) From Time of Administration up to 24 Hours Post Dosing (AUC24h) of Norethindrone
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Average Steady-State Plasma Concentration (Cavg) of Ethinylestradiol
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Average Steady-State Plasma Concentration (Cavg) of Norethindrone
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Percentage Fluctuation (FI) of Ethinylestradiol
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Percentage Fluctuation (FI) of Norethindrone
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Ratio of Individual Cmax Values Between Test and Reference Treatment (Ratio Cmax, test/ref) of Ethinylestradiol
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Ratio of Individual Cmax Values Between Test and Reference Treatment (Ratio Cmax, test/ref) of Norethindrone
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Ratio of Individual AUC24h Values Between Test and Reference Treatment (Ratio AUC24h, test/ref) of Ethinylestradiol
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
measure: Ratio of Individual AUC24h Values Between Test and Reference Treatment (Ratio AUC24h, test/ref) of Norethindrone
timeFrame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 49 of Cycle II; Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle III
Secondary outcomes:
Other outcomes:
Locations:
city: Merksem
country: Belgium
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: