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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02652650
• Other study ID #: CR108093
• Secondary ID: 63623872FLZ10092
• Status: Completed
• Phase: Phase 1
• First received: January 8, 2016
• Last updated: June 3, 2016
• Start date: December 2015
• Est. completion date: June 2016

Study information

• Verified date: June 2016
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Ethinylestradiol
Participants will receive 35 microgram (mcg) alone once daily (qd) for 21 days on Days 1 to 21 (Cycle I: lead-in) during first OC cycle; Days 29 to 49 (Cycle II: OC alone, reference) during the second OC cycle and Days 57 to 77 during third OC cycle.
• Norethindrone
Participants will receive 1 milligram (mg) alone once daily (qd) for 21 days on Days 1 to 21 (Cycle I: lead-in) during first OC cycle; Days 29 to 49 (Cycle II: OC alone, reference) during the second OC cycle and Days 57 to 77 during third OC cycle.
• JNJ-63623872
Participants will receive 600 mg twice daily (bid) for 5 days on Days 73 to 77 (Cycle III: OC plus JNJ-63623872, test) during third OC cycle under fed conditions.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of JNJ-63623872	Ctrough is the observed analyte concentration just prior to the beginning or at the end of a dosing Interval.	Post-dose on Days 75 and 76 of Cycle III	No
Primary	Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of JNJ-63623872	Ctrough is the observed analyte concentration just prior to the beginning or at the end of a dosing Interval.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	No
Primary	Observed Analyte Concentration at 12 Hours Post Dosing (C12h) of JNJ-63623872	C12h is the observed analyte concentration at 12 hours post dosing.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	No
Primary	Minimum Observed Analyte Concentration (Cmin) of JNJ-63623872	Cmin is the minimum observed analyte concentration.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	No
Primary	Maximum Observed Analyte Concentration (Cmax) of JNJ-63623872	Cmax is the maximum observed analyte concentration.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	No
Primary	Time To Reach The Maximum Observed Analyte Concentration (Tmax) of JNJ-63623872	Tmax is the actual sampling time to reach the maximum observed analyte concentration.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	No
Primary	Area Under the Analyte Concentration versus Time Curve (AUC) From Time of Administration up to 12 Hours Post Dosing (AUC12h) of JNJ-63623872	AUC12h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 12 hours post dosing.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	No
Primary	Average Steady-State Plasma Concentration (Cavg) of JNJ-63623872	Cavg is the average steady-state plasma concentration.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	No
Primary	Percentage Fluctuation (FI) of JNJ-63623872	FI is the percentage fluctuation(variation between maximum and minimum concentration at steady-state), calculated as: 100 multiplied ([Cmax - Cmin] / Cavg).	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 77 of Cycle II	No
Primary	Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of Ethinylestradiol	Ctrough is the observed analyte concentration just prior to the beginning or at the end of a dosing Interval.	Post-dose on Days 47 and 48 of Cycle II; post-dose on Days 75 and 76 of Cycle III	No
Primary	Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of Norethindrone	Ctrough is the observed analyte concentration just prior to the beginning or at the end of a dosing Interval.	Post-dose on Days 47 and 48 of Cycle II; post-dose on Days 75 and 76 of Cycle III	No
Primary	Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of Ethinylestradiol	Ctrough is the observed analyte concentration just prior to the beginning or at the end of a dosing Interval.	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	No
Primary	Observed Analyte Concentration Just Prior to the Beginning or at the End of a Dosing Interval (Ctrough) of Norethindrone	Ctrough is the observed analyte concentration just prior to the beginning or at the end of a dosing Interval.	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	No
Primary	Observed Analyte Concentration at 24 Hours Post Dosing (C24h) of Ethinylestradiol	C24h is the observed analyte concentration at 24 hours post dosing.	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	No
Primary	Observed Analyte Concentration at 24 Hours Post Dosing (C24h) of Norethindrone	C24h is the observed analyte concentration at 24 hours post dosing.	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	No
Primary	Minimum Observed Analyte Concentration (Cmin) of Ethinylestradiol	Cmin is the minimum observed analyte concentration.	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	No
Primary	Minimum Observed Analyte Concentration (Cmin) of Norethindrone	Cmin is the minimum observed analyte concentration.	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	No
Primary	Maximum Observed Analyte Concentration (Cmax) of Ethinylestradiol	Cmax is the maximum observed analyte concentration.	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	No
Primary	Maximum Observed Analyte Concentration (Cmax) of Norethindrone	Cmax is the maximum observed analyte concentration.	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	No
Primary	Time To Reach The Maximum Observed Analyte Concentration (Tmax) of Ethinylestradiol	Tmax is the actual sampling time to reach the maximum observed analyte concentration.	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	No
Primary	Time To Reach The Maximum Observed Analyte Concentration (Tmax) of Norethindrone	Tmax is the actual sampling time to reach the maximum observed analyte concentration.	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	No
Primary	Area Under the Analyte Concentration versus Time Curve (auc) From Time of Administration up to 24 Hours Post Dosing (AUC24h) of Ethinylestradiol	AUC24h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 24 hours post dosing.	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	No
Primary	Area Under the Analyte Concentration versus Time Curve (auc) From Time of Administration up to 24 Hours Post Dosing (AUC24h) of Norethindrone	AUC24h is the area under the analyte concentration versus time curve (AUC) from time of administration up to 24 hours post dosing.	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	No
Primary	Average Steady-State Plasma Concentration (Cavg) of Ethinylestradiol	Cavg average steady-state plasma concentration.	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	No
Primary	Average Steady-State Plasma Concentration (Cavg) of Norethindrone	Cavg average steady-state plasma concentration.	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	No
Primary	Percentage Fluctuation (FI) of Ethinylestradiol	FI is the percentage fluctuation(variation between maximum and minimum concentration at steady-state), calculated as: 100 multiplied ([Cmax - Cmin] / Cavg).	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	No
Primary	Percentage Fluctuation (FI) of Norethindrone	FI is the percentage fluctuation(variation between maximum and minimum concentration at steady-state), calculated as: 100 multiplied ([Cmax - Cmin] / Cavg).	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	No
Primary	Ratio of Individual Cmax Values Between Test and Reference Treatment (Ratio Cmax, test/ref) of Ethinylestradiol	Ratio Cmax, test/ref is the ratio of individual Cmax values between test and reference treatment 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	No
Primary	Ratio of Individual Cmax Values Between Test and Reference Treatment (Ratio Cmax, test/ref) of Norethindrone	Ratio Cmax, test/ref is the ratio of individual Cmax values between test and reference treatment 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	No
Primary	Ratio of Individual AUC24h Values Between Test and Reference Treatment (Ratio AUC24h, test/ref) of Ethinylestradiol	Ratio AUC24h, test/ref is the ratio of individual AUC24h values between test and reference treatment 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	No
Primary	Ratio of Individual AUC24h Values Between Test and Reference Treatment (Ratio AUC24h, test/ref) of Norethindrone	Ratio AUC24h, test/ref is the ratio of individual AUC24h values between test and reference treatment 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	No