<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/NCT02217527</url>
  </required_header>
  <id_info>
    <org_study_id>UH3-PRO14070319</org_study_id>
    <secondary_id>UH3TR000958</secondary_id>
    <nct_id>NCT02217527</nct_id>
  </id_info>
  <brief_title>Test of Novel Drug for Smoking Cessation</brief_title>
  <acronym>UH3-P2</acronym>
  <official_title>Development of a Novel Therapeutic for Smoking Cessation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chengappa, K.N. Roy, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study will assess a novel active drug vs. placebo on ability to reduce smoking and aid&#xD;
      cessation during a one-week &quot;practice&quot; quit period for each condition in smokers with a high&#xD;
      interest in quitting (i.e. crossover design). Medication effects on reducing withdrawal and&#xD;
      cognitive impairment will help assess the mechanism to support quit smoking attempts.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We aim to test the proof of principal that an alpha-7 PAM drug, JNJ-39393406, promotes&#xD;
      smoking cessation when compared to placebo. We have developed, tested, and validated an&#xD;
      efficient Phase 2a screening procedure that optimally combines the validity of randomized&#xD;
      clinical trials with the practicality of lab- based medication studies. Notably, it employs a&#xD;
      within-subject, cross-over design comparing active versus placebo effects on quitting smoking&#xD;
      to maximize statistical power without a large sample, in contrast to the large samples needed&#xD;
      for between-groups randomized treatment conditions. Using this procedure, we will evaluate&#xD;
      effects of JNJ-39393406 vs. placebo on short-term smoking abstinence in smokers who already&#xD;
      have a high interest in quitting soon. We predict that, compared with placebo, JNJ-39393406&#xD;
      will increase days of abstinence, identifying initial evidence of efficacy for smoking&#xD;
      cessation. Our main dependent measure is days of very stringent biochemically validated&#xD;
      (expired CO&lt;5 ppm) 24-hr smoking abstinence, with post-quit withdrawal and cognitive function&#xD;
      as secondary measures. Potential for adverse side-effects will be assessed at each visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">January 2018</completion_date>
  <primary_completion_date type="Actual">July 2017</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Crossover of active JNJ vs. placebo for 2 weeks each, involving 1 week of dose run-up and 1 week of attempting to quit each day on that drug condition. A one-week washout separates these drug conditions, which are administered in counter-balanced order.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quit Status</measure>
    <time_frame>up to one week each drug phase (0-5)</time_frame>
    <description>Complete abstinence from smoking for 24 hr is counted as a &quot;quit day&quot; and is assessed daily from Mon-Fri for just one week, on the JNJ active drug and one week on placebo. This same Mon-Fri procedure for one week (only) is done for both drug phases. Total outcome in each drug condition therefore is number of quit days out of the five assessment days (range 0-5).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Minnesota Nicotine Withdrawal Scale (MNWS) During Attempt to Quit on Active JNJ Drug and on Placebo</measure>
    <time_frame>only on days quit while on JNJ or on placebo</time_frame>
    <description>Severity of withdrawal symptoms will be assessed with standard self-report measure of Minnesota Nicotine Withdrawal Scale (MNWS) each quit day during one week only on active JNJ, and each quit day during one week on placebo. Ratings are made on 0-100 visual analog scale, with 0=&quot;not at all&quot; to 100=&quot;very much&quot;, and are averaged to create a total score also ranging from 0-100. Higher scores indicate more severe withdrawal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Function on Continuous Performance Task (CPT) for Those With CO&lt;10 During First Assessment Day (Mon) of Attempt to Quit Smoking During Both JNJ and Plac Quit Periods</measure>
    <time_frame>first day during quit week on JNJ, and during quit week on placebo.</time_frame>
    <description>This measure of cognitive performance (mean of median speed of correct responding on computer keyboard to letters and numbers) was assessed only on Monday (day 1) of the 0-5 days during each drug/placebo condition. Data only from those shown to have CO&lt;10 ppm were analyzed, to confirm responding during abstinence while on drug/placebo condition. Cognitive testing consisted of standard Continuous Performance Task (CPT), on active JNJ and on placebo phases. This measure is assessed to determine potential mechanism of drug efficacy in relieving disrupted cognitive processing function caused by tobacco deprivation and withdrawal.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Smoking Cessation</condition>
  <arm_group>
    <arm_group_label>JNJ Active Drug</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>200 mg (100 mg b.i.d.) Active JNJ Drug used to assess quitting for one week, as part of crossover design. This JNJ experimental compound has NO name, just a company number.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Pill</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo pill used for one week quit attempt, as part of crossover design.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Active JNJ Drug</intervention_name>
    <description>200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.</description>
    <arm_group_label>JNJ Active Drug</arm_group_label>
    <arm_group_label>Placebo Pill</arm_group_label>
    <other_name>JNJ-39393406</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo pill</intervention_name>
    <description>Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.</description>
    <arm_group_label>JNJ Active Drug</arm_group_label>
    <arm_group_label>Placebo Pill</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Healthy male and female dependent smokers wanting to quit soon&#xD;
&#xD;
        -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of non-smoked nicotine products&#xD;
&#xD;
          -  Already enrolled in cessation program.&#xD;
&#xD;
               -  Recent alcohol or substance dependence (≤ 3 months)&#xD;
&#xD;
               -  Women who are pregnant, planning a pregnancy, or lactating; all female&#xD;
                  participants shall undergo a pregnancy test at screening and will be excluded if&#xD;
                  positive.&#xD;
&#xD;
               -  Serious or unstable medical disorder within the past 3 months&#xD;
&#xD;
          -  Epilepsy&#xD;
&#xD;
               -  Current diagnosis (within last 6-months) of abnormal cardiac rhythms; unstable&#xD;
                  cardiovascular disease e.g. stroke, myocardial infarction in the last 6 months&#xD;
&#xD;
               -  Evidence impaired liver function test (LFT)&#xD;
&#xD;
               -  Evidence of kidney failure&#xD;
&#xD;
               -  Any subject with a history of hematological cancers examples: leukemia, lymphoma&#xD;
                  etc.&#xD;
&#xD;
               -  Any clinically significant hematological laboratory abnormality.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kenneth Perkins, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Univ of PIttsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Univ of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <results_first_submitted>June 18, 2018</results_first_submitted>
  <results_first_submitted_qc>July 16, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">August 15, 2018</results_first_posted>
  <last_update_submitted>July 16, 2018</last_update_submitted>
  <last_update_submitted_qc>July 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Kenneth A. Perkins, PhD.</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>crossover</keyword>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT02217527/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>All enrolled after confirmation of eligibility were then assigned to Order 1 or Order 2.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Order 1--JNJ Active Then Plac</title>
          <description>200 mg (100 mg b.i.d.) Active JNJ Drug used to assess quitting for one week, as part of crossover design, followed by trying to quit for one week on placebo. This JNJ experimental compound has NO name, just a company number.&#xD;
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.&#xD;
Placebo pill: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.</description>
        </group>
        <group group_id="P2">
          <title>Order 2--Placebo Then JNJ Active</title>
          <description>Placebo pill used for one week quit attempt, as part of crossover design, followed by one week of trying to quit on active JNJ drug.&#xD;
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.&#xD;
Placebo pill: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Drug Condition 1: First Study Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Drug Condition 2: Second Study Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Healthy smokers interested in permanently quitting smoking within the next few months.</population>
      <group_list>
        <group group_id="B1">
          <title>Order 1--JNJ Active Then Plac</title>
          <description>200 mg (100 mg b.i.d.) Active JNJ Drug used to assess quitting for one week, as part of crossover design, then one week trying to quit on placebo. This JNJ experimental compound has NO name, just a company number.&#xD;
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.&#xD;
Placebo pill: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.</description>
        </group>
        <group group_id="B2">
          <title>Order 2--Placebo Then JNJ Active</title>
          <description>Placebo pill used for one week quit attempt, as part of crossover design, then one week trying to quit on active JNJ drug.&#xD;
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.&#xD;
Placebo pill: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.</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="18"/>
            <count group_id="B2" value="18"/>
            <count group_id="B3" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fagerstrom Test of Nicotine Dependence (FTND) scale score</title>
          <description>All completed the Fagerstrom Test of Nicotine Dependence (FTND) scale score at baseline, to assess severity of current nicotine dependence. FTND scores range from 0-10, and higher scores index more severe dependence. These scores were not used to determine eligibility, just to characterize dependence severity.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.9" spread="1.5"/>
                    <measurement group_id="B2" value="4.9" spread="1.5"/>
                    <measurement group_id="B3" value="4.9" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Quit Status</title>
        <description>Complete abstinence from smoking for 24 hr is counted as a &quot;quit day&quot; and is assessed daily from Mon-Fri for just one week, on the JNJ active drug and one week on placebo. This same Mon-Fri procedure for one week (only) is done for both drug phases. Total outcome in each drug condition therefore is number of quit days out of the five assessment days (range 0-5).</description>
        <time_frame>up to one week each drug phase (0-5)</time_frame>
        <population>Smokers trying to quit each day during 5-day period on active JNJ, and then during 5-day period on placebo, in crossover design.</population>
        <group_list>
          <group group_id="O1">
            <title>Order 1--JNJ Active Then Plac</title>
            <description>200 mg (100 mg b.i.d.) Active JNJ Drug used to assess quitting for one week, as part of crossover design, then one week quitting on placebo. This JNJ experimental compound has NO name, just a company number.&#xD;
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.&#xD;
Placebo pill: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.</description>
          </group>
          <group group_id="O2">
            <title>Order 2--Placebo Then JNJ Active</title>
            <description>Placebo pill used for one week quit attempt, as part of crossover design, then one week quitting on active JNJ drug.&#xD;
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.&#xD;
Placebo pill: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.</description>
          </group>
        </group_list>
        <measure>
          <title>Quit Status</title>
          <description>Complete abstinence from smoking for 24 hr is counted as a &quot;quit day&quot; and is assessed daily from Mon-Fri for just one week, on the JNJ active drug and one week on placebo. This same Mon-Fri procedure for one week (only) is done for both drug phases. Total outcome in each drug condition therefore is number of quit days out of the five assessment days (range 0-5).</description>
          <population>Smokers trying to quit each day during 5-day period on active JNJ, and then during 5-day period on placebo, in crossover design.</population>
          <units>number of days quit</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>on JNJ</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" spread="1.3"/>
                    <measurement group_id="O2" value="0.2" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>on placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="1.5"/>
                    <measurement group_id="O2" value="0.5" spread="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Minnesota Nicotine Withdrawal Scale (MNWS) During Attempt to Quit on Active JNJ Drug and on Placebo</title>
        <description>Severity of withdrawal symptoms will be assessed with standard self-report measure of Minnesota Nicotine Withdrawal Scale (MNWS) each quit day during one week only on active JNJ, and each quit day during one week on placebo. Ratings are made on 0-100 visual analog scale, with 0=&quot;not at all&quot; to 100=&quot;very much&quot;, and are averaged to create a total score also ranging from 0-100. Higher scores indicate more severe withdrawal.</description>
        <time_frame>only on days quit while on JNJ or on placebo</time_frame>
        <population>Withdrawal severity on quit days for smokers interested in quitting soon, while attempting to quit briefly during one week on active JNJ or one week on placebo.</population>
        <group_list>
          <group group_id="O1">
            <title>Order 1--JNJ Active Then Plac</title>
            <description>200 mg (100 mg b.i.d.) Active JNJ Drug used to assess quitting for one week, as part of crossover design, then one week quitting on placebo. This JNJ experimental compound has NO name, just a company number.&#xD;
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.&#xD;
Placebo pill: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.</description>
          </group>
          <group group_id="O2">
            <title>Order 2--Placebo Then JNJ Active</title>
            <description>Placebo pill used for one week quit attempt, as part of crossover design, then one week quitting on active JNJ drug.&#xD;
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.&#xD;
Placebo pill: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.</description>
          </group>
        </group_list>
        <measure>
          <title>Minnesota Nicotine Withdrawal Scale (MNWS) During Attempt to Quit on Active JNJ Drug and on Placebo</title>
          <description>Severity of withdrawal symptoms will be assessed with standard self-report measure of Minnesota Nicotine Withdrawal Scale (MNWS) each quit day during one week only on active JNJ, and each quit day during one week on placebo. Ratings are made on 0-100 visual analog scale, with 0=&quot;not at all&quot; to 100=&quot;very much&quot;, and are averaged to create a total score also ranging from 0-100. Higher scores indicate more severe withdrawal.</description>
          <population>Withdrawal severity on quit days for smokers interested in quitting soon, while attempting to quit briefly during one week on active JNJ or one week on placebo.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>on active JNJ</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.4" spread="8.1"/>
                    <measurement group_id="O2" value="24.0" spread="23.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>on placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.5" spread="15.2"/>
                    <measurement group_id="O2" value="23.1" spread="19.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Function on Continuous Performance Task (CPT) for Those With CO&lt;10 During First Assessment Day (Mon) of Attempt to Quit Smoking During Both JNJ and Plac Quit Periods</title>
        <description>This measure of cognitive performance (mean of median speed of correct responding on computer keyboard to letters and numbers) was assessed only on Monday (day 1) of the 0-5 days during each drug/placebo condition. Data only from those shown to have CO&lt;10 ppm were analyzed, to confirm responding during abstinence while on drug/placebo condition. Cognitive testing consisted of standard Continuous Performance Task (CPT), on active JNJ and on placebo phases. This measure is assessed to determine potential mechanism of drug efficacy in relieving disrupted cognitive processing function caused by tobacco deprivation and withdrawal.</description>
        <time_frame>first day during quit week on JNJ, and during quit week on placebo.</time_frame>
        <population>Only those participants able to quit or sharply limit smoking exposure during both JNJ and the placebo phases of testing, defined as those with CO&lt;10 during both tests of cognitive performance when tobacco abstinent.</population>
        <group_list>
          <group group_id="O1">
            <title>Order 1--JNJ Active Then Plac</title>
            <description>200 mg (100 mg b.i.d.) Active JNJ Drug used to assess quitting for one week, as part of crossover design, then one week quitting on placebo. This JNJ experimental compound has NO name, just a company number.&#xD;
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.&#xD;
Placebo pill: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.</description>
          </group>
          <group group_id="O2">
            <title>Order 2--Placebo Then JNJ Active</title>
            <description>Placebo pill used for one week quit attempt, as part of crossover design, then one week quitting on active JNJ drug.&#xD;
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.&#xD;
Placebo pill: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Function on Continuous Performance Task (CPT) for Those With CO&lt;10 During First Assessment Day (Mon) of Attempt to Quit Smoking During Both JNJ and Plac Quit Periods</title>
          <description>This measure of cognitive performance (mean of median speed of correct responding on computer keyboard to letters and numbers) was assessed only on Monday (day 1) of the 0-5 days during each drug/placebo condition. Data only from those shown to have CO&lt;10 ppm were analyzed, to confirm responding during abstinence while on drug/placebo condition. Cognitive testing consisted of standard Continuous Performance Task (CPT), on active JNJ and on placebo phases. This measure is assessed to determine potential mechanism of drug efficacy in relieving disrupted cognitive processing function caused by tobacco deprivation and withdrawal.</description>
          <population>Only those participants able to quit or sharply limit smoking exposure during both JNJ and the placebo phases of testing, defined as those with CO&lt;10 during both tests of cognitive performance when tobacco abstinent.</population>
          <units>ms time of correct responding</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>on active JNJ</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="444.3" spread="69.3"/>
                    <measurement group_id="O2" value="443.3" spread="32.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>on placebo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="434.2" spread="33.5"/>
                    <measurement group_id="O2" value="439.2" spread="28.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Assessed over the 2 weeks of med use on each condition (active JNJ, or placebo) per participant and ending within 1 week post-participation.</time_frame>
      <desc>Participants were asked about any adverse effects during each visit. If they reported any, study staff probed for details and contacted study physician who oversaw physical exam at screening to discuss next steps - e.g. monitor and further follow up visits until resolved, or refer to other medical specialists, or to WPIC laboratory for further testing until resolved. Participants also received lab tests via blood sample and EKG at one visit during each 2-week med use period.</desc>
      <group_list>
        <group group_id="E1">
          <title>While on Active JNJ</title>
          <description>200 mg (100 mg b.i.d.) Active JNJ Drug used to assess quitting for one week, as part of crossover design, followed by one week of quitting on placebo. This JNJ experimental compound has NO name, just a company number.&#xD;
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug used for one week while attempting to briefly quit smoking on Mon-Fri of that week.</description>
        </group>
        <group group_id="E2">
          <title>While on Placebo</title>
          <description>Placebo pill used for one week quit attempt, as part of crossover design, followed by one week of quitting on active JNJ drug.&#xD;
Placebo pill: Placebo pill taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="5" subjects_at_risk="36"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal EKG</sub_title>
                <description>sinus bradycardia, incomplete right bundle branch QRS pattern</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>heart racing</sub_title>
                <description>heart racing, sadness</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>self-reported nausea</sub_title>
                <description>Self-report of nausea</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>diarrhea</sub_title>
                <description>Self-reported complaint of diahrrea</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>body aches</sub_title>
                <description>Self-reported body aches</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="36"/>
              </event>
              <event>
                <sub_title>feeling of subjective panic</sub_title>
                <description>Shortness of breath, dizziness, overwhelming feeling</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>swelling in feet</sub_title>
                <description>swelling, numbness, and pain in feet while walking</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>self-reported skin rash</sub_title>
                <description>Skin rash report</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="36"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="36"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Our findings could be specific to the brief duration, procedures used, and single dose tested in this cross-over study.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Kenneth A. Perkins, Prof of Psychiatry</name_or_title>
      <organization>Univ of Pittsburgh</organization>
      <phone>412-246-5395</phone>
      <email>perkinska@upmc.edu</email>
    </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/NCT02217527
org study id: UH3-PRO14070319
secondary id: UH3TR000958
nct id: NCT02217527
lead sponsor: 
collaborator: 
has dmc: Yes
The study will assess a novel active drug vs. placebo on ability to reduce smoking and aid
      cessation during a one-week "practice" quit period for each condition in smokers with a high
      interest in quitting (i.e. crossover design). Medication effects on reducing withdrawal and
      cognitive impairment will help assess the mechanism to support quit smoking attempts.
We aim to test the proof of principal that an alpha-7 PAM drug, JNJ-39393406, promotes
      smoking cessation when compared to placebo. We have developed, tested, and validated an
      efficient Phase 2a screening procedure that optimally combines the validity of randomized
      clinical trials with the practicality of lab- based medication studies. Notably, it employs a
      within-subject, cross-over design comparing active versus placebo effects on quitting smoking
      to maximize statistical power without a large sample, in contrast to the large samples needed
      for between-groups randomized treatment conditions. Using this procedure, we will evaluate
      effects of JNJ-39393406 vs. placebo on short-term smoking abstinence in smokers who already
      have a high interest in quitting soon. We predict that, compared with placebo, JNJ-39393406
      will increase days of abstinence, identifying initial evidence of efficacy for smoking
      cessation. Our main dependent measure is days of very stringent biochemically validated
      (expired CO<5 ppm) 24-hr smoking abstinence, with post-quit withdrawal and cognitive function
      as secondary measures. Potential for adverse side-effects will be assessed at each visit.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Crossover of active JNJ vs. placebo for 2 weeks each, involving 1 week of dose run-up and 1 week of attempting to quit each day on that drug condition. A one-week washout separates these drug conditions, which are administered in counter-balanced order.
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Quit Status
time frame: up to one week each drug phase (0-5)
description: Complete abstinence from smoking for 24 hr is counted as a "quit day" and is assessed daily from Mon-Fri for just one week, on the JNJ active drug and one week on placebo. This same Mon-Fri procedure for one week (only) is done for both drug phases. Total outcome in each drug condition therefore is number of quit days out of the five assessment days (range 0-5).
measure: Minnesota Nicotine Withdrawal Scale (MNWS) During Attempt to Quit on Active JNJ Drug and on Placebo
time frame: only on days quit while on JNJ or on placebo
description: Severity of withdrawal symptoms will be assessed with standard self-report measure of Minnesota Nicotine Withdrawal Scale (MNWS) each quit day during one week only on active JNJ, and each quit day during one week on placebo. Ratings are made on 0-100 visual analog scale, with 0="not at all" to 100="very much", and are averaged to create a total score also ranging from 0-100. Higher scores indicate more severe withdrawal.
measure: Cognitive Function on Continuous Performance Task (CPT) for Those With CO<10 During First Assessment Day (Mon) of Attempt to Quit Smoking During Both JNJ and Plac Quit Periods
time frame: first day during quit week on JNJ, and during quit week on placebo.
description: This measure of cognitive performance (mean of median speed of correct responding on computer keyboard to letters and numbers) was assessed only on Monday (day 1) of the 0-5 days during each drug/placebo condition. Data only from those shown to have CO<10 ppm were analyzed, to confirm responding during abstinence while on drug/placebo condition. Cognitive testing consisted of standard Continuous Performance Task (CPT), on active JNJ and on placebo phases. This measure is assessed to determine potential mechanism of drug efficacy in relieving disrupted cognitive processing function caused by tobacco deprivation and withdrawal.
arm group label: JNJ Active Drug
arm group type: Experimental
description: 200 mg (100 mg b.i.d.) Active JNJ Drug used to assess quitting for one week, as part of crossover design. This JNJ experimental compound has NO name, just a company number.
arm group label: Placebo Pill
arm group type: Experimental
description: Placebo pill used for one week quit attempt, as part of crossover design.
intervention type: Drug
intervention name: Active JNJ Drug
description: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.
arm group label: JNJ Active Drug
arm group label: Placebo Pill
other name: JNJ-39393406
intervention type: Drug
intervention name: Placebo pill
description: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.
arm group label: JNJ Active Drug
arm group label: Placebo Pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kenneth Perkins, PhD
role: Principal Investigator
affiliation: Univ of PIttsburgh
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Kenneth A. Perkins, PhD.
investigator title: Professor
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Our findings could be specific to the brief duration, procedures used, and single dose tested in this cross-over study.
point of contact: 