A Study to Investigate the Effect of JNJ-63623872 at Steady-state on the Steady-state Pharmacokinetics of Ethinylestradiol and Norethindrone

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Ethinylestradiol; Drug: Norethindrone; Drug: JNJ-63623872

• Registration Number: NCT02652650
• Lead Sponsor: Janssen Research & Development, LLC

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.

Study Timeline

• Study Start: 2015-12
• Study First Submitted: 2016-01-08
• Study First Submitted QC: 2016-01-11
• Study First Posted: 2016-01-12
• Status Verified: 2016-06
• Primary Completion: 2016-06
• Study Completion: 2016-06
• Last Update Submitted: 2016-06-03
• Last Update Posted: 2016-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 18

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ethinylestradiol/Norethindrone	Ethinylestradiol	During the first oral contraceptive (OC) cycle participants will receive ethinylestradiol/norethindrone 35 microgram (mcg)/1 milligram (mg) alone once daily (qd) for 21 days on Days 1 to 21 (Cycle I: lead-in). During the second OC cycle (from Day 29 to Day 56), participants will receive ethinylestradiol/norethindrone 35 mcg/1 mg alone qd for 21 days on Days 29 to 49 (Cycle II: OC alone, reference). During the third OC cycle (from Day 57 to Day 84), participants will receive ethinylestradiol/norethindrone 35 mcg/1 mg qd for 21 days on Days 57 to 77 and in addition JNJ-63623872, 600 mg twice daily (bid) for 5 days on Days 73 to 77 (Cycle III: OC plus JNJ-63623872, test).
Ethinylestradiol/Norethindrone	Norethindrone	During the first oral contraceptive (OC) cycle participants will receive ethinylestradiol/norethindrone 35 microgram (mcg)/1 milligram (mg) alone once daily (qd) for 21 days on Days 1 to 21 (Cycle I: lead-in). During the second OC cycle (from Day 29 to Day 56), participants will receive ethinylestradiol/norethindrone 35 mcg/1 mg alone qd for 21 days on Days 29 to 49 (Cycle II: OC alone, reference). During the third OC cycle (from Day 57 to Day 84), participants will receive ethinylestradiol/norethindrone 35 mcg/1 mg qd for 21 days on Days 57 to 77 and in addition JNJ-63623872, 600 mg twice daily (bid) for 5 days on Days 73 to 77 (Cycle III: OC plus JNJ-63623872, test).
Ethinylestradiol/Norethindrone	JNJ-63623872	During the first oral contraceptive (OC) cycle participants will receive ethinylestradiol/norethindrone 35 microgram (mcg)/1 milligram (mg) alone once daily (qd) for 21 days on Days 1 to 21 (Cycle I: lead-in). During the second OC cycle (from Day 29 to Day 56), participants will receive ethinylestradiol/norethindrone 35 mcg/1 mg alone qd for 21 days on Days 29 to 49 (Cycle II: OC alone, reference). During the third OC cycle (from Day 57 to Day 84), participants will receive ethinylestradiol/norethindrone 35 mcg/1 mg qd for 21 days on Days 57 to 77 and in addition JNJ-63623872, 600 mg twice daily (bid) for 5 days on Days 73 to 77 (Cycle III: OC plus JNJ-63623872, test).

Primary Outcome Measures

Name	Time	Method
Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of JNJ-63623872	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	Ctrough is the observed analyte concentration just prior to the beginning or at the end of a dosing Interval.
Observed Analyte Concentration at 12 Hours Post Dosing (C12h) of JNJ-63623872	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	C12h is the observed analyte concentration at 12 hours post dosing.
Minimum Observed Analyte Concentration (Cmin) of JNJ-63623872	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	Cmin is the minimum observed analyte concentration.
Maximum Observed Analyte Concentration (Cmax) of JNJ-63623872	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	Cmax is the maximum observed analyte concentration.
Time To Reach The Maximum Observed Analyte Concentration (Tmax) of JNJ-63623872	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	Tmax is the actual sampling time to reach the maximum observed analyte concentration.
Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 12 Hours Post Dosing (AUC12h) of JNJ-63623872	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	AUC12h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 12 hours post dosing.
Average Steady-State Plasma Concentration (Cavg) of JNJ-63623872	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	Cavg is the average steady-state plasma concentration.
Percentage Fluctuation (FI) of JNJ-63623872	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	FI is the percentage fluctuation(variation between maximum and minimum concentration at steady-state), calculated as: 100 multiplied (\[Cmax - Cmin\] / Cavg).
Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of Ethinylestradiol	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	Ctrough is the observed analyte concentration just prior to the beginning or at the end of a dosing Interval.
Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of Norethindrone	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	Ctrough is the observed analyte concentration just prior to the beginning or at the end of a dosing Interval.
Observed Analyte Concentration at 24 Hours Post Dosing (C24h) of Ethinylestradiol	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	C24h is the observed analyte concentration at 24 hours post dosing.
Observed Analyte Concentration at 24 Hours Post Dosing (C24h) of Norethindrone	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	C24h is the observed analyte concentration at 24 hours post dosing.
Minimum Observed Analyte Concentration (Cmin) of Ethinylestradiol	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	Cmin is the minimum observed analyte concentration.
Minimum Observed Analyte Concentration (Cmin) of Norethindrone	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	Cmin is the minimum observed analyte concentration.
Maximum Observed Analyte Concentration (Cmax) of Norethindrone	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	Cmax is the maximum observed analyte concentration.
Time To Reach The Maximum Observed Analyte Concentration (Tmax) of Ethinylestradiol	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	Tmax is the actual sampling time to reach the maximum observed analyte concentration.
Time To Reach The Maximum Observed Analyte Concentration (Tmax) of Norethindrone	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	Tmax is the actual sampling time to reach the maximum observed analyte concentration.
Area Under the Analyte Concentration versus Time Curve (auc) From Time of Administration up to 24 Hours Post Dosing (AUC24h) of Ethinylestradiol	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	AUC24h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 24 hours post dosing.
Area Under the Analyte Concentration versus Time Curve (auc) From Time of Administration up to 24 Hours Post Dosing (AUC24h) of Norethindrone	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	AUC24h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 24 hours post dosing.
Average Steady-State Plasma Concentration (Cavg) of Ethinylestradiol	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	Cavg average steady-state plasma concentration.
Average Steady-State Plasma Concentration (Cavg) of Norethindrone	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	Cavg average steady-state plasma concentration.
Percentage Fluctuation (FI) of Ethinylestradiol	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	FI is the percentage fluctuation(variation between maximum and minimum concentration at steady-state), calculated as: 100 multiplied (\[Cmax - Cmin\] / Cavg).
Percentage Fluctuation (FI) of Norethindrone	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	FI is the percentage fluctuation(variation between maximum and minimum concentration at steady-state), calculated as: 100 multiplied (\[Cmax - Cmin\] / Cavg).
Ratio of Individual Cmax Values Between Test and Reference Treatment (Ratio Cmax, test/ref) of Ethinylestradiol	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	Ratio Cmax, test/ref is the ratio of individual Cmax values between test and reference treatment of ethinylestradiol.
Ratio of Individual Cmax Values Between Test and Reference Treatment (Ratio Cmax, test/ref) of Norethindrone	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	Ratio Cmax, test/ref is the ratio of individual Cmax values between test and reference treatment of Norethindrone.
Maximum Observed Analyte Concentration (Cmax) of Ethinylestradiol	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	Cmax is the maximum observed analyte concentration.
Ratio of Individual AUC24h Values Between Test and Reference Treatment (Ratio AUC24h, test/ref) of Ethinylestradiol	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	Ratio AUC24h, test/ref is the ratio of individual AUC24h values between test and reference treatment of Ethinylestradiol.
Ratio of Individual AUC24h Values Between Test and Reference Treatment (Ratio AUC24h, test/ref) of Norethindrone	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	Ratio AUC24h, test/ref is the ratio of individual AUC24h values between test and reference treatment of Norethindrone.