<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03274297</url>
  </required_header>
  <id_info>
    <org_study_id>CR108360</org_study_id>
    <secondary_id>2017-002186-22</secondary_id>
    <secondary_id>RWJ10553CON4001</secondary_id>
    <nct_id>NCT03274297</nct_id>
  </id_info>
  <brief_title>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</brief_title>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the bioequivalence of the hormones (ie,&#xD;
      norelgestromin [NGMN] and ethinyl estradiol [EE]) from the transdermal contraceptive patch&#xD;
      and to evaluate the adhesion of the transdermal contraceptive patch using the newly sourced&#xD;
      adhesive component, as compared to the currently marketed EVRA patch.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 20, 2017</start_date>
  <completion_date type="Actual">May 7, 2018</completion_date>
  <primary_completion_date type="Actual">May 7, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Steady-State Concentration (Css) for Norelgestromin (NGMN)</measure>
    <time_frame>48 to 168 hours post-dose</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Steady-State Concentration (Css) for Ethinyl Estradiol (EE)</measure>
    <time_frame>48 to 168 hours post-dose</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Time 168 hours Post-dose (AUC[0-168]) for NGMN</measure>
    <time_frame>Pre-dose to 168 hours post-dose</time_frame>
    <description>Area under the concentration versus time curve from zero (patch application) to 168 hours of NGMN in plasma will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Time 168 hours Post-dose (AUC[0-168]) for EE</measure>
    <time_frame>Pre-dose to 168 hours post-dose</time_frame>
    <description>Area under the concentration versus time curve from zero (patch application) to 168 hours of EE in plasma will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Time 240 hours Post-dose (AUC[0-240]) for NGMN</measure>
    <time_frame>Pre-dose to 240 hours post-dose</time_frame>
    <description>Area under the concentration versus time curve from zero (patch application) to 240 hours of NGMN in plasma will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Time 240 hours Post-dose (AUC[0-240]) for EE</measure>
    <time_frame>Pre-dose to 240 hours post-dose</time_frame>
    <description>Area under the concentration versus time curve from zero (patch application) to 240 hours of EE in plasma will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Infinite Time (AUC[0-infinity]) for NGMN</measure>
    <time_frame>Pre-dose to 240 hours post-dose</time_frame>
    <description>Area under the concentration versus time curve from zero (patch application) to infinite time of NGMN in plasma will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Infinite Time (AUC[0-infinity]) for EE</measure>
    <time_frame>Pre-dose to 240 hours post-dose</time_frame>
    <description>Area under the concentration versus time curve from zero (patch application) to infinite time of EE in plasma will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative Adhesion Percentage Ratio</measure>
    <time_frame>Baseline (Day 1) and every 24 hours after patch application up to patch removal at 168 hours (Day 8)</time_frame>
    <description>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 (&gt;) 90-100% of the patch area adheres; 1= &gt;80-90% of the patch area adheres; 2= &gt;70-80% of the patch area adheres; 3= &gt;60-70% of the patch area adheres; 4= &gt;50-60% of the patch area adheres; 5= 0-less than or equal to (&lt;=) 50% of the patch area adheres.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Irritation Potential</measure>
    <time_frame>Screening, pre-dose, 168.5 and 192 hours post-dose</time_frame>
    <description>Percentage of participants with specific application site reactions will be summarized for each treatment.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Group 1: Sequence AB (Right/Left)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: Sequence BA (Right/Left)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3: Sequence AB (Left/Right)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4: Sequence BA (Left/Right)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EVRA patch (NGMN+EE) (Treatment A) (Reference)</intervention_name>
    <description>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.</description>
    <arm_group_label>Group 1: Sequence AB (Right/Left)</arm_group_label>
    <arm_group_label>Group 2: Sequence BA (Right/Left)</arm_group_label>
    <arm_group_label>Group 3: Sequence AB (Left/Right)</arm_group_label>
    <arm_group_label>Group 4: Sequence BA (Left/Right)</arm_group_label>
    <other_name>RWJ10553</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HMW PIB patch (NGMN+EE) (Treatment B) (Test)</intervention_name>
    <description>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.</description>
    <arm_group_label>Group 1: Sequence AB (Right/Left)</arm_group_label>
    <arm_group_label>Group 2: Sequence BA (Right/Left)</arm_group_label>
    <arm_group_label>Group 3: Sequence AB (Left/Right)</arm_group_label>
    <arm_group_label>Group 4: Sequence BA (Left/Right)</arm_group_label>
    <other_name>RWJ10553</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant has a body mass index (BMI) between 18 and 30 kilogram per meter square&#xD;
             (kg/m^2), inclusive, and body weight not to exceed 100 kilogram&#xD;
&#xD;
          -  Participant must be healthy on the basis of physical examination, medical history,&#xD;
             vital signs, and 12-lead electrocardiogram (ECG) performed at screening. This will be&#xD;
             documented and signed by the investigator in the source document&#xD;
&#xD;
          -  Participant must have a negative serum (beta-human chorionic gonadotropin) pregnancy&#xD;
             test at screening and negative urine pregnancy tests on Day -1 of each treatment&#xD;
             period&#xD;
&#xD;
          -  Participant must be willing and able to adhere to the prohibitions and restrictions&#xD;
             specified in this protocol&#xD;
&#xD;
          -  Participant must be surgically sterile with intact ovaries, abstinent, or, if sexually&#xD;
             active, be practicing an effective method of non-hormonal birth control (example [eg],&#xD;
             intrauterine device [IUD], double barrier method, male partner sterilization) before&#xD;
             admission and throughout the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participant has a history of or current clinically significant medical illness&#xD;
             including (but not limited to) cardiac arrhythmias or other cardiac disease,&#xD;
             hematologic disease, coagulation disorders (including any abnormal bleeding or blood&#xD;
             dyscrasias), lipid abnormalities, significant pulmonary disease, including&#xD;
             bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency,&#xD;
             thyroid disease, neurologic or psychiatric disease, infection, cholelithiasis (gall&#xD;
             stone disease), chronic idiopathic jaundice, family history of cholestatic jaundice,&#xD;
             or any other illness that the investigator considers should exclude the participant or&#xD;
             that could interfere with the interpretation of the study results&#xD;
&#xD;
          -  Participant has clinically significant abnormal values for hematology, biochemistry,&#xD;
             or urinalysis at screening as deemed appropriate by the investigator&#xD;
&#xD;
          -  Participant has abnormal thyroid stimulating hormone level at screening&#xD;
&#xD;
          -  Participant has clinically significant abnormal 12-lead ECG, vital signs, or physical&#xD;
             examination at screening as deemed appropriate by the investigator&#xD;
&#xD;
          -  Participant has a history or presence of disorders commonly accepted as&#xD;
             contraindications to sex hormonal therapy including, but not limited to, the&#xD;
             following: a) Deep vein thrombophlebitis or thromboembolic disorders; b) Cerebral&#xD;
             vascular or coronary artery disease, chronic untreated hypertension, or migraines; c)&#xD;
             Benign or malignant liver tumor that developed during the use of oral contraceptives&#xD;
             or other estrogen-containing products; d) Known or suspected estrogen-dependent&#xD;
             neoplasia&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Pharmacology Unit</name>
      <address>
        <city>Merksem</city>
        <zip>2170</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&amp;amp;parentIdentifier=CR108360&amp;amp;attachmentIdentifier=d571bf10-3740-4505-8684-14039f9d6a41&amp;amp;fileName=CR108360_CSR.pdf&amp;amp;versionIdentifier=</url>
    <description>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</description>
  </link>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <last_update_submitted>May 7, 2019</last_update_submitted>
  <last_update_submitted_qc>May 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tissue Adhesions</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03274297
org study id: CR108360
secondary id: 2017-002186-22
secondary id: RWJ10553CON4001
nct id: NCT03274297
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Mean Steady-State Concentration (Css) for Norelgestromin (NGMN)
time frame: 48 to 168 hours post-dose
description: 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.
measure: Mean Steady-State Concentration (Css) for Ethinyl Estradiol (EE)
time frame: 48 to 168 hours post-dose
description: 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.
measure: Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Time 168 hours Post-dose (AUC[0-168]) for NGMN
time frame: Pre-dose to 168 hours post-dose
description: Area under the concentration versus time curve from zero (patch application) to 168 hours of NGMN in plasma will be assessed.
measure: Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Time 168 hours Post-dose (AUC[0-168]) for EE
time frame: Pre-dose to 168 hours post-dose
description: Area under the concentration versus time curve from zero (patch application) to 168 hours of EE in plasma will be assessed.
measure: Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Time 240 hours Post-dose (AUC[0-240]) for NGMN
time frame: Pre-dose to 240 hours post-dose
description: Area under the concentration versus time curve from zero (patch application) to 240 hours of NGMN in plasma will be assessed.
measure: Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Time 240 hours Post-dose (AUC[0-240]) for EE
time frame: Pre-dose to 240 hours post-dose
description: Area under the concentration versus time curve from zero (patch application) to 240 hours of EE in plasma will be assessed.
measure: Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Infinite Time (AUC[0-infinity]) for NGMN
time frame: Pre-dose to 240 hours post-dose
description: Area under the concentration versus time curve from zero (patch application) to infinite time of NGMN in plasma will be assessed.
measure: Area Under the Plasma Concentration-Time Curve From Time 0 (Patch Application) to Infinite Time (AUC[0-infinity]) for EE
time frame: Pre-dose to 240 hours post-dose
description: Area under the concentration versus time curve from zero (patch application) to infinite time of EE in plasma will be assessed.
measure: Cumulative Adhesion Percentage Ratio
time frame: Baseline (Day 1) and every 24 hours after patch application up to patch removal at 168 hours (Day 8)
description: 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.
measure: Irritation Potential
time frame: Screening, pre-dose, 168.5 and 192 hours post-dose
description: Percentage of participants with specific application site reactions will be summarized for each treatment.
arm group label: Group 1: Sequence AB (Right/Left)
arm group type: Experimental
description: 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.
arm group label: Group 2: Sequence BA (Right/Left)
arm group type: Experimental
description: 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.
arm group label: Group 3: Sequence AB (Left/Right)
arm group type: Experimental
description: 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.
arm group label: Group 4: Sequence BA (Left/Right)
arm group type: Experimental
description: 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.
intervention type: Drug
intervention name: EVRA patch (NGMN+EE) (Treatment A) (Reference)
description: 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.
arm group label: Group 1: Sequence AB (Right/Left)
arm group label: Group 2: Sequence BA (Right/Left)
arm group label: Group 3: Sequence AB (Left/Right)
arm group label: Group 4: Sequence BA (Left/Right)
other name: RWJ10553
intervention type: Drug
intervention name: HMW PIB patch (NGMN+EE) (Treatment B) (Test)
description: 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.
arm group label: Group 1: Sequence AB (Right/Left)
arm group label: Group 2: Sequence BA (Right/Left)
arm group label: Group 3: Sequence AB (Left/Right)
arm group label: Group 4: Sequence BA (Left/Right)
other name: RWJ10553
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
country: Belgium
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&amp;parentIdentifier=CR108360&amp;attachmentIdentifier=d571bf10-3740-4505-8684-14039f9d6a41&amp;fileName=CR108360_CSR.pdf&amp;versionIdentifier=
description: 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
responsible party type: Sponsor
mesh term: Tissue Adhesions