<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/NCT01702519</url>
  </required_header>
  <id_info>
    <org_study_id>RH01418</org_study_id>
    <nct_id>NCT01702519</nct_id>
  </id_info>
  <brief_title>A Pharmacokinetic Evaluation of Two Nicotine Patches in Smokers</brief_title>
  <official_title>A Pharmacokinetic Evaluation of Two Nicotine Patches in Smokers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bioequivalence study to confirm that a NTS with a polyisobutylene (PIB) adhesive from an&#xD;
      alternative supplier delivers the same nicotine blood profile as that of the currently&#xD;
      approved NTS with a polyisobutylene adhesive from the current supplier.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2012</start_date>
  <completion_date type="Actual">March 2012</completion_date>
  <primary_completion_date type="Actual">March 2012</primary_completion_date>
  <phase>Phase 1</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>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Curve From Time 0 to the Last Quantifiable Sample, AUC(0-t)</measure>
    <time_frame>Baseline to 32 hours</time_frame>
    <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Area under the plasma concentration time curve from zero and extrapolated to the time of last quantifiable sample was determined by plasma concentration time profile of nicotine. Blood samples were drawn at the following time intervals: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after the application of the patch. Patch was then removed after the collection of 24 hour blood sample. AUC(0 -t) was based on the baseline adjusted nicotine plasma concentration data.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Measured Plasma Concentration (Cmax)</measure>
    <time_frame>Baseline to 32 hours</time_frame>
    <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Maximum plasma nicotine concentration was determined from plasma concentration time profiles. Blood samples were drawn at various time points: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after application the patch. Patch was then removed after the collection of 24 hour blood sample. Cmax was based on the baseline adjusted nicotine plasma concentration data.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration Time Curve Between Zero and Infinity, AUC (0-inf)</measure>
    <time_frame>Baseline to 32 hours</time_frame>
    <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Area under the plasma nicotine concentration time curve from zero extrapolated to infinity was determined by plasma concentration time profile of nicotine. Blood samples drawn at various time points including: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after wearing the patch. Patch was then removed after the collection of 24 hour blood sample. AUC(0 -inf) was based on the baseline adjusted nicotine plasma concentration data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Plasma Concentration (Tmax)</measure>
    <time_frame>Baseline to 32 hours</time_frame>
    <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Time to Maximum Plasma Concentration was determined from plasma concentration time profiles. Blood samples were drawn at various time points; immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after application of the patch. Patch was then removed after the collection of 24 hour blood sample. Tmax was based on the baseline adjusted nicotine plasma concentration data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Half-life (t1/2)</measure>
    <time_frame>Baseline to 32 hours</time_frame>
    <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. The elimination half-life of nicotine was determined by from plasma concentration time profiles. Blood samples were drawn at several time points: immediately pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after the application of the patch. Patch was then removed after the collection of 24 hour blood sample. Plasma half-life (t1/2) was based on the baseline adjusted nicotine plasma concentration data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Elimination (Kel)</measure>
    <time_frame>Baseline to 32 hours</time_frame>
    <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Elimination rate constant for nicotine was determined from plasma concentration time profiles. Blood samples were drawn at several time points: immediately pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours the application of the patch. Patch was then removed after the collection of 24 hour blood sample. Elimination rate constant for nicotine was based on the baseline adjusted nicotine plasma concentration data.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Smoking</condition>
  <arm_group>
    <arm_group_label>Reference</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>nicotine transdermal patch with the existing polyisobutylene adhesive</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatement</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>nicotine transdermal patch with the alternate polyisobutylene adhesive</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nicotine</intervention_name>
    <description>nicotine transdermal patch</description>
    <arm_group_label>Reference</arm_group_label>
    <arm_group_label>Treatement</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  BMI 19-27 kg/m2&#xD;
&#xD;
          -  smokes &gt;10 cigarettes per day for preceeding 6 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  inability to stop smoking during study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Celerion NEBRASKA</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2015</verification_date>
  <study_first_submitted>October 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2012</study_first_posted>
  <results_first_submitted>September 5, 2013</results_first_submitted>
  <results_first_submitted_qc>February 9, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 11, 2015</results_first_posted>
  <last_update_submitted>March 19, 2015</last_update_submitted>
  <last_update_submitted_qc>March 19, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 20, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nicotine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited at a single clinical site in the US.</recruitment_details>
      <pre_assignment_details>A total of 128 participants were screened, of which only 40 were randomized into the study. 71 participants did not meet the study eligibility criteria, 4 were lost to follow up, 6 withdrew consent while the remaining 7 were not randomized due to the other reason.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Test Then Reference Patch</title>
          <description>Participants first applied a test nicotine patch (21 mg) containing test adhesive for 24 hours, and then entered a washout period of 48 hours. Post-washout, they applied reference nicotine patch containing Reference adhesive (21 mg) for additional 24 hours.</description>
        </group>
        <group group_id="P2">
          <title>Reference Then Test Patch</title>
          <description>Participants first applied the Reference nicotine patch (21 mg) containing test adhesive for 24 hours, and then entered a washout period of 48 hours. Post-washout, they applied the Test nicotine patch containing reference adhesive (21 mg) for additional 24 hours.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Test Then Reference Patch</title>
          <description>Participants first applied a test nicotine patch (21 mg) containing test adhesive for 24 hours, and then entered a washout period of 48 hours. Post-washout, they applied reference nicotine patch containing Reference adhesive (21 mg) for additional 24 hours.</description>
        </group>
        <group group_id="B2">
          <title>Reference Then Test Patch</title>
          <description>Participants first applied the Reference nicotine patch (21 mg) containing test adhesive for 24 hours, and then entered a washout period of 48 hours. Post-washout, they applied the Test nicotine patch containing reference adhesive (21 mg) for additional 24 hours.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
            <count group_id="B2" value="20"/>
            <count group_id="B3" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36.3" spread="11.33"/>
                    <measurement group_id="B2" value="31.4" spread="11.59"/>
                    <measurement group_id="B3" value="33.8" spread="11.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Curve From Time 0 to the Last Quantifiable Sample, AUC(0-t)</title>
        <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Area under the plasma concentration time curve from zero and extrapolated to the time of last quantifiable sample was determined by plasma concentration time profile of nicotine. Blood samples were drawn at the following time intervals: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after the application of the patch. Patch was then removed after the collection of 24 hour blood sample. AUC(0 -t) was based on the baseline adjusted nicotine plasma concentration data.</description>
        <time_frame>Baseline to 32 hours</time_frame>
        <population>Per Protocol Population, which consisted of all randomized participants who took at least one dose of the study treatment, did not have any protocol deviation, and provided enough pharmacokinetic data as determined by the pharmacokineticist.</population>
        <group_list>
          <group group_id="O1">
            <title>Test Patch</title>
            <description>Participants were instructed to wear transdermal nicotine patch (21 mg) with test adhesive, for 24 hours.</description>
          </group>
          <group group_id="O2">
            <title>Reference Patch</title>
            <description>Participants were instructed to wear transdermal nicotine patch (21 mg) with the reference adhesive, for 24 hours.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Curve From Time 0 to the Last Quantifiable Sample, AUC(0-t)</title>
          <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Area under the plasma concentration time curve from zero and extrapolated to the time of last quantifiable sample was determined by plasma concentration time profile of nicotine. Blood samples were drawn at the following time intervals: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after the application of the patch. Patch was then removed after the collection of 24 hour blood sample. AUC(0 -t) was based on the baseline adjusted nicotine plasma concentration data.</description>
          <population>Per Protocol Population, which consisted of all randomized participants who took at least one dose of the study treatment, did not have any protocol deviation, and provided enough pharmacokinetic data as determined by the pharmacokineticist.</population>
          <units>nanogram (ng)*hour (hr)/milliliter (mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="494.54" spread="115.075" lower_limit="0.92" upper_limit="1.0"/>
                    <measurement group_id="O2" value="528.43" spread="129.762" lower_limit="0.91" upper_limit="0.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis considered no difference between the two treatments.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Bio-equivalence was established if 90% confidence interval (CI) of the ratio (Test/Ref) of geometric means was included in the limit of 0.80 - 1.25</non_inferiority_desc>
            <param_type>Treatment Ratio</param_type>
            <param_value>0.946</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.912</ci_lower_limit>
            <ci_upper_limit>0.982</ci_upper_limit>
            <estimate_desc>The ratio between the geometric means of the test and reference formulations was calculated</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Measured Plasma Concentration (Cmax)</title>
        <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Maximum plasma nicotine concentration was determined from plasma concentration time profiles. Blood samples were drawn at various time points: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after application the patch. Patch was then removed after the collection of 24 hour blood sample. Cmax was based on the baseline adjusted nicotine plasma concentration data.</description>
        <time_frame>Baseline to 32 hours</time_frame>
        <population>Per Protocol Population, which consisted of all randomized participants who took at least one dose of the study treatment, did not have any protocol deviation, and provided enough pharmacokinetic data as determined by the pharmacokineticist.</population>
        <group_list>
          <group group_id="O1">
            <title>Test Patch</title>
            <description>Participants were instructed to wear transdermal nicotine patch (21 mg) with test adhesive, for 24 hours.</description>
          </group>
          <group group_id="O2">
            <title>Reference Patch</title>
            <description>Participants were instructed to wear transdermal nicotine patch (21 mg) with the reference adhesive, for 24 hours.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Measured Plasma Concentration (Cmax)</title>
          <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Maximum plasma nicotine concentration was determined from plasma concentration time profiles. Blood samples were drawn at various time points: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after application the patch. Patch was then removed after the collection of 24 hour blood sample. Cmax was based on the baseline adjusted nicotine plasma concentration data.</description>
          <population>Per Protocol Population, which consisted of all randomized participants who took at least one dose of the study treatment, did not have any protocol deviation, and provided enough pharmacokinetic data as determined by the pharmacokineticist.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.31" spread="4.986"/>
                    <measurement group_id="O2" value="23.50" spread="5.917"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis considered no difference between the treatments.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Bioequivalence was established if 90% confidence interval (CI) of the ratio (Test/Ref) of geometric means was included in the limit of 0.80 - 1.25.</non_inferiority_desc>
            <param_type>Treatment Ratio</param_type>
            <param_value>0.962</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.92</ci_lower_limit>
            <ci_upper_limit>1.00</ci_upper_limit>
            <estimate_desc>The ratio between the geometric means of the test and reference formulations was calculated</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration Time Curve Between Zero and Infinity, AUC (0-inf)</title>
        <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Area under the plasma nicotine concentration time curve from zero extrapolated to infinity was determined by plasma concentration time profile of nicotine. Blood samples drawn at various time points including: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after wearing the patch. Patch was then removed after the collection of 24 hour blood sample. AUC(0 -inf) was based on the baseline adjusted nicotine plasma concentration data.</description>
        <time_frame>Baseline to 32 hours</time_frame>
        <population>Per Protocol Population, which consisted of all randomized participants who took at least one dose of the study treatment, did not have any protocol deviation, and provided enough pharmacokinetic data as determined by the pharmacokineticist.</population>
        <group_list>
          <group group_id="O1">
            <title>Test Patch</title>
            <description>Participants were instructed to wear transdermal nicotine patch (21 mg) with test adhesive, for 24 hours</description>
          </group>
          <group group_id="O2">
            <title>Reference Patch</title>
            <description>Participants were instructed to wear transdermal nicotine patch (21 mg) with reference adhesive, for 24 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration Time Curve Between Zero and Infinity, AUC (0-inf)</title>
          <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Area under the plasma nicotine concentration time curve from zero extrapolated to infinity was determined by plasma concentration time profile of nicotine. Blood samples drawn at various time points including: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after wearing the patch. Patch was then removed after the collection of 24 hour blood sample. AUC(0 -inf) was based on the baseline adjusted nicotine plasma concentration data.</description>
          <population>Per Protocol Population, which consisted of all randomized participants who took at least one dose of the study treatment, did not have any protocol deviation, and provided enough pharmacokinetic data as determined by the pharmacokineticist.</population>
          <units>ng*h/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="505.13" spread="118.939"/>
                    <measurement group_id="O2" value="541.15" spread="134.854"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Plasma Concentration (Tmax)</title>
        <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Time to Maximum Plasma Concentration was determined from plasma concentration time profiles. Blood samples were drawn at various time points; immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after application of the patch. Patch was then removed after the collection of 24 hour blood sample. Tmax was based on the baseline adjusted nicotine plasma concentration data.</description>
        <time_frame>Baseline to 32 hours</time_frame>
        <population>Per protocol population, which included all randomized participants who took at least one dose of the drug, did not have any protocol deviations and whose data was considered evaluable by the pharmacokineticist.</population>
        <group_list>
          <group group_id="O1">
            <title>Test Patch</title>
            <description>Participants were instructed to wear transdermal nicotine patch with test adhesive, for 24 hours.</description>
          </group>
          <group group_id="O2">
            <title>Reference Patch</title>
            <description>Participants were instructed to wear transdermal nicotine patch with reference adhesive, for 24 hours.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Plasma Concentration (Tmax)</title>
          <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Time to Maximum Plasma Concentration was determined from plasma concentration time profiles. Blood samples were drawn at various time points; immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after application of the patch. Patch was then removed after the collection of 24 hour blood sample. Tmax was based on the baseline adjusted nicotine plasma concentration data.</description>
          <population>Per protocol population, which included all randomized participants who took at least one dose of the drug, did not have any protocol deviations and whose data was considered evaluable by the pharmacokineticist.</population>
          <units>hrs</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.00" lower_limit="0.5" upper_limit="24.0"/>
                    <measurement group_id="O2" value="17.99" lower_limit="2.0" upper_limit="24.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma Half-life (t1/2)</title>
        <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. The elimination half-life of nicotine was determined by from plasma concentration time profiles. Blood samples were drawn at several time points: immediately pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after the application of the patch. Patch was then removed after the collection of 24 hour blood sample. Plasma half-life (t1/2) was based on the baseline adjusted nicotine plasma concentration data</description>
        <time_frame>Baseline to 32 hours</time_frame>
        <population>Per-prorocol population, which included all randomized participants who received at least one dose of the study treatment, had no protocol violation, and whose data was considered evaluable by the pharmacokineticist.</population>
        <group_list>
          <group group_id="O1">
            <title>Test Patch</title>
            <description>Participants were instructed to wear transdermal nicotine patch with test adhesive, for 24 hours.</description>
          </group>
          <group group_id="O2">
            <title>Reference Patch</title>
            <description>Participants were instructed to wear transdermal nicotine patch with reference adhesive, for 24 hours.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Half-life (t1/2)</title>
          <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. The elimination half-life of nicotine was determined by from plasma concentration time profiles. Blood samples were drawn at several time points: immediately pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after the application of the patch. Patch was then removed after the collection of 24 hour blood sample. Plasma half-life (t1/2) was based on the baseline adjusted nicotine plasma concentration data</description>
          <population>Per-prorocol population, which included all randomized participants who received at least one dose of the study treatment, had no protocol violation, and whose data was considered evaluable by the pharmacokineticist.</population>
          <units>Hrs</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.55" lower_limit="2.0" upper_limit="3.5"/>
                    <measurement group_id="O2" value="2.59" lower_limit="2.0" upper_limit="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Elimination (Kel)</title>
        <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Elimination rate constant for nicotine was determined from plasma concentration time profiles. Blood samples were drawn at several time points: immediately pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours the application of the patch. Patch was then removed after the collection of 24 hour blood sample. Elimination rate constant for nicotine was based on the baseline adjusted nicotine plasma concentration data.</description>
        <time_frame>Baseline to 32 hours</time_frame>
        <population>Per protocol population, which included all randomized participants who took at least one dose of the study medications, had no protocol violations, and whose data was considered evaluable by the pharmacokineticist.</population>
        <group_list>
          <group group_id="O1">
            <title>Test Patch</title>
            <description>Participants were instructed to wear transdermal nicotine patch with test adhesive, for 24 hours.</description>
          </group>
          <group group_id="O2">
            <title>Reference Patch</title>
            <description>Participants were instructed to wear transdermal nicotine patch with reference adhesive, for 24 hours.</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Elimination (Kel)</title>
          <description>Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Elimination rate constant for nicotine was determined from plasma concentration time profiles. Blood samples were drawn at several time points: immediately pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours the application of the patch. Patch was then removed after the collection of 24 hour blood sample. Elimination rate constant for nicotine was based on the baseline adjusted nicotine plasma concentration data.</description>
          <population>Per protocol population, which included all randomized participants who took at least one dose of the study medications, had no protocol violations, and whose data was considered evaluable by the pharmacokineticist.</population>
          <units>1/hr</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.27" lower_limit="0.2" upper_limit="0.3"/>
                    <measurement group_id="O2" value="0.27" lower_limit="0.2" upper_limit="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs were collected from the start of the smoking abstinence sequestration period and until five days following last administration of the study treatments</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Test Patch</title>
          <description>Participants were instructed to wear transdermal nicotine patch with test adhesive, for 24 hours.</description>
        </group>
        <group group_id="E2">
          <title>Reference Patch</title>
          <description>Participants were instructed to wear transdermal nicotine patch with reference adhesive, for 24 hours</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 15.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="38"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Application Site Erythema</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="38"/>
                <counts group_id="E2" events="20" subjects_affected="20" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Application Site Pruritus</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="38"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal Dreams</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>GSK Response Center</name_or_title>
      <organization>GlaxoSmithKline</organization>
      <phone>866-435-7343</phone>
    </point_of_contact>
  </clinical_results>
</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/NCT01702519
org study id: RH01418
nct id: NCT01702519
lead sponsor: 
has dmc: No
Bioequivalence study to confirm that a NTS with a polyisobutylene (PIB) adhesive from an
      alternative supplier delivers the same nicotine blood profile as that of the currently
      approved NTS with a polyisobutylene adhesive from the current supplier.
allocation: Randomized
intervention model: Crossover Assignment
masking: Single (Outcomes Assessor)
measure: Area Under the Curve From Time 0 to the Last Quantifiable Sample, AUC(0-t)
time frame: Baseline to 32 hours
description: Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Area under the plasma concentration time curve from zero and extrapolated to the time of last quantifiable sample was determined by plasma concentration time profile of nicotine. Blood samples were drawn at the following time intervals: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after the application of the patch. Patch was then removed after the collection of 24 hour blood sample. AUC(0 -t) was based on the baseline adjusted nicotine plasma concentration data.
measure: Maximum Measured Plasma Concentration (Cmax)
time frame: Baseline to 32 hours
description: Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Maximum plasma nicotine concentration was determined from plasma concentration time profiles. Blood samples were drawn at various time points: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after application the patch. Patch was then removed after the collection of 24 hour blood sample. Cmax was based on the baseline adjusted nicotine plasma concentration data.
measure: Area Under the Concentration Time Curve Between Zero and Infinity, AUC (0-inf)
time frame: Baseline to 32 hours
description: Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Area under the plasma nicotine concentration time curve from zero extrapolated to infinity was determined by plasma concentration time profile of nicotine. Blood samples drawn at various time points including: immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after wearing the patch. Patch was then removed after the collection of 24 hour blood sample. AUC(0 -inf) was based on the baseline adjusted nicotine plasma concentration data.
measure: Time to Maximum Plasma Concentration (Tmax)
time frame: Baseline to 32 hours
description: Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Time to Maximum Plasma Concentration was determined from plasma concentration time profiles. Blood samples were drawn at various time points; immediately pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after application of the patch. Patch was then removed after the collection of 24 hour blood sample. Tmax was based on the baseline adjusted nicotine plasma concentration data.
measure: Plasma Half-life (t1/2)
time frame: Baseline to 32 hours
description: Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. The elimination half-life of nicotine was determined by from plasma concentration time profiles. Blood samples were drawn at several time points: immediately pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours after the application of the patch. Patch was then removed after the collection of 24 hour blood sample. Plasma half-life (t1/2) was based on the baseline adjusted nicotine plasma concentration data
measure: Rate of Elimination (Kel)
time frame: Baseline to 32 hours
description: Following randomization, the nicotine patches; reference nicotine patch or test nicotine patch (as per the assigned sequence), were applied on participant's upper back or arm. Elimination rate constant for nicotine was determined from plasma concentration time profiles. Blood samples were drawn at several time points: immediately pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, 25, 26, 28, and 32 hours the application of the patch. Patch was then removed after the collection of 24 hour blood sample. Elimination rate constant for nicotine was based on the baseline adjusted nicotine plasma concentration data.
arm group label: Reference
arm group type: Active Comparator
description: nicotine transdermal patch with the existing polyisobutylene adhesive
arm group label: Treatement
arm group type: Active Comparator
description: nicotine transdermal patch with the alternate polyisobutylene adhesive
intervention type: Drug
intervention name: nicotine
description: nicotine transdermal patch
arm group label: Reference
arm group label: Treatement
criteria: 
gender: All
minimum age: 19 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: United States
responsible party type: Sponsor
mesh term: Nicotine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 