A Study to Evaluate Bioequivalence and Adhesion of a Transdermal Contraceptive Patch Manufactured With Newly Sourced Adhesive Components and Currently Marketed EVRA in Healthy Adult Women

A Randomized, Double-blind, 2-Way Crossover Bioequivalence and Adhesion Study of a Transdermal Contraceptive Patch Manufactured With Newly Sourced Adhesive Components and Currently Marketed EVRA® in Healthy Adult Women

The purpose of this study is to determine the bioequivalence of the hormones (ie, norelgestromin [NGMN] and ethinyl estradiol [EE]) from the transdermal contraceptive patch and to evaluate the adhesion of the transdermal contraceptive patch using the newly sourced adhesive component, as compared to the currently marketed EVRA patch.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: EVRA patch (NGMN+EE) (Treatment A) (Reference); Drug: HMW PIB patch (NGMN+EE) (Treatment B) (Test)

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium, 2170
    • Clinical Pharmacology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Participant has a body mass index (BMI) between 18 and 30 kilogram per meter square (kg/m^2), inclusive, and body weight not to exceed 100 kilogram
• Participant must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. This will be documented and signed by the investigator in the source document
• Participant must have a negative serum (beta-human chorionic gonadotropin) pregnancy test at screening and negative urine pregnancy tests on Day -1 of each treatment period
• Participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
• Participant must be surgically sterile with intact ovaries, abstinent, or, if sexually active, be practicing an effective method of non-hormonal birth control (example [eg], intrauterine device [IUD], double barrier method, male partner sterilization) before admission and throughout the study

Exclusion Criteria:

• Participant has a history of or 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, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, infection, cholelithiasis (gall stone disease), chronic idiopathic jaundice, family history of cholestatic jaundice, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
• Participant has clinically significant abnormal values for hematology, biochemistry, or urinalysis at screening as deemed appropriate by the investigator
• Participant has abnormal thyroid stimulating hormone level at screening
• Participant has clinically significant abnormal 12-lead ECG, vital signs, or physical examination at screening as deemed appropriate by the investigator
• Participant has a history or presence of disorders commonly accepted as contraindications to sex hormonal therapy including, but not limited to, the following: a) Deep vein thrombophlebitis or thromboembolic disorders; b) Cerebral vascular or coronary artery disease, chronic untreated hypertension, or migraines; c) Benign or malignant liver tumor that developed during the use of oral contraceptives or other estrogen-containing products; d) Known or suspected estrogen-dependent neoplasia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Sequence AB (Right/Left); A single patch of currently marketed EVRA patch (Treatment A) will be applied to the right buttock of participants on Day 1 of treatment period 1, followed by application of a single patch of transdermal contraceptive using the newly sourced adhesive component HMW PIB (Treatment B) to left buttock of participants on Day 1 of treatment period 2. The treatment periods will be separated by a washout period of 21 days.	Drug: EVRA patch (NGMN+EE) (Treatment A) (Reference); A single transdermal contraceptive patch of EVRA (NGMN + EE) containing 6 milligram (mg) of the progestin NGMN and 600 microgram (mcg) of the EE will be applied to the buttock (right or left) of participants on Day 1 of each treatment period and is removed 7 days after patch application, ie, on Day 8.; Other Names: RWJ10553; Drug: HMW PIB patch (NGMN+EE) (Treatment B) (Test); A single transdermal contraceptive HMW PIB (NGMN + EE) patch containing 6 mg of the progestin NGMN and 600 mcg of the EE will be applied to the buttock (right or left) of participants on Day 1 of each treatment period and is removed 7 days after patch application, ie, on Day 8.; Other Names: RWJ10553
Experimental: Group 2: Sequence BA (Right/Left); Treatment B will be applied to the right buttock of participants on Day 1 in Period 1 followed by Treatment A to the left buttock on Day 1 in Period 2. The treatment periods will be separated by a washout period of 21 days.	Drug: EVRA patch (NGMN+EE) (Treatment A) (Reference); A single transdermal contraceptive patch of EVRA (NGMN + EE) containing 6 milligram (mg) of the progestin NGMN and 600 microgram (mcg) of the EE will be applied to the buttock (right or left) of participants on Day 1 of each treatment period and is removed 7 days after patch application, ie, on Day 8.; Other Names: RWJ10553; Drug: HMW PIB patch (NGMN+EE) (Treatment B) (Test); A single transdermal contraceptive HMW PIB (NGMN + EE) patch containing 6 mg of the progestin NGMN and 600 mcg of the EE will be applied to the buttock (right or left) of participants on Day 1 of each treatment period and is removed 7 days after patch application, ie, on Day 8.; Other Names: RWJ10553
Experimental: Group 3: Sequence AB (Left/Right); Treatment A will be applied to the left buttock of participants on Day 1 in Period 1 followed by Treatment B to the right buttock on Day 1 in Period 2. The treatment periods will be separated by a washout period of 21 days.	Drug: EVRA patch (NGMN+EE) (Treatment A) (Reference); A single transdermal contraceptive patch of EVRA (NGMN + EE) containing 6 milligram (mg) of the progestin NGMN and 600 microgram (mcg) of the EE will be applied to the buttock (right or left) of participants on Day 1 of each treatment period and is removed 7 days after patch application, ie, on Day 8.; Other Names: RWJ10553; Drug: HMW PIB patch (NGMN+EE) (Treatment B) (Test); A single transdermal contraceptive HMW PIB (NGMN + EE) patch containing 6 mg of the progestin NGMN and 600 mcg of the EE will be applied to the buttock (right or left) of participants on Day 1 of each treatment period and is removed 7 days after patch application, ie, on Day 8.; Other Names: RWJ10553
Experimental: Group 4: Sequence BA (Left/Right); Treatment B will be applied to the left buttock of participants on Day 1 in Period 1 followed by Treatment A to the right buttock on Day 1 in Period 2. The treatment periods will be separated by a washout period of 21 days.	Drug: EVRA patch (NGMN+EE) (Treatment A) (Reference); A single transdermal contraceptive patch of EVRA (NGMN + EE) containing 6 milligram (mg) of the progestin NGMN and 600 microgram (mcg) of the EE will be applied to the buttock (right or left) of participants on Day 1 of each treatment period and is removed 7 days after patch application, ie, on Day 8.; Other Names: RWJ10553; Drug: HMW PIB patch (NGMN+EE) (Treatment B) (Test); A single transdermal contraceptive HMW PIB (NGMN + EE) patch containing 6 mg of the progestin NGMN and 600 mcg of the EE will be applied to the buttock (right or left) of participants on Day 1 of each treatment period and is removed 7 days after patch application, ie, on Day 8.; Other Names: RWJ10553

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Steady-State Concentration (Css) for Norelgestromin (NGMN)	Mean steady-state concentration for NGMN after patch application, will be calculated as the mean concentration between 48 hours and 168 hours after patch application.	48 to 168 hours post-dose
Mean Steady-State Concentration (Css) for Ethinyl Estradiol (EE)	Mean steady-state concentration for EE after patch application, will be calculated as the mean concentration between 48 hours and 168 hours after patch application.	48 to 168 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Time 168 hours Post-dose (AUC[0-168]) for NGMN	Area under the concentration versus time curve from zero (patch application) to 168 hours of NGMN in plasma will be assessed.	Pre-dose to 168 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Time 168 hours Post-dose (AUC[0-168]) for EE	Area under the concentration versus time curve from zero (patch application) to 168 hours of EE in plasma will be assessed.	Pre-dose to 168 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Time 240 hours Post-dose (AUC[0-240]) for NGMN	Area under the concentration versus time curve from zero (patch application) to 240 hours of NGMN in plasma will be assessed.	Pre-dose to 240 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Time 240 hours Post-dose (AUC[0-240]) for EE	Area under the concentration versus time curve from zero (patch application) to 240 hours of EE in plasma will be assessed.	Pre-dose to 240 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Infinite Time (AUC[0-infinity]) for NGMN	Area under the concentration versus time curve from zero (patch application) to infinite time of NGMN in plasma will be assessed.	Pre-dose to 240 hours post-dose
Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Infinite Time (AUC[0-infinity]) for EE	Area under the concentration versus time curve from zero (patch application) to infinite time of EE in plasma will be assessed.	Pre-dose to 240 hours post-dose
Cumulative Adhesion Percentage Ratio	Adhesion of patches will be assessed in accordance with the European Medicines Agency (EMA) 0-5 scoring system. An estimated percentage of adhesion, to a whole integer, will be obtained (EMA 0-5 [percentage (%)] scoring). Estimated percentages of adhesion and corresponding EMA 0-5 score at each interval will be recorded in each participant's electronic case report form. The scoring system for adhesion of transdermal patches is indicated as follows: 0= greater than (>) 90-100% of the patch area adheres; 1= >80-90% of the patch area adheres; 2= >70-80% of the patch area adheres; 3= >60-70% of the patch area adheres; 4= >50-60% of the patch area adheres; 5= 0-less than or equal to (<=) 50% of the patch area adheres.	Baseline (Day 1) and every 24 hours after patch application up to patch removal at 168 hours (Day 8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Irritation Potential	Percentage of participants with specific application site reactions will be summarized for each treatment.	Screening, pre-dose, 168.5 and 192 hours post-dose

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

Helpful Links

• A Randomized, Double-blind, 2-Way Crossover, Bioequivalence and Adhesion Study of a Transdermal Contraceptive Patch Manufactured With Newly Sourced Adhesive Components and Currently Marketed EVRA® in Healthy Adult Women

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2017
• Primary Completion (Actual): May 7, 2018
• Study Completion (Actual): May 7, 2018

Study Registration Dates

• First Submitted: September 5, 2017
• First Submitted That Met QC Criteria: September 5, 2017
• First Posted (Actual): September 6, 2017

Study Record Updates

• Last Update Posted (Actual): May 9, 2019
• Last Update Submitted That Met QC Criteria: May 7, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix; Tissue Adhesions
• Other Study ID Numbers: CR108360; 2017-002186-22 (EudraCT Number); RWJ10553CON4001 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No