<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/NCT02230384</url>
  </required_header>
  <id_info>
    <org_study_id>PRO14060338</org_study_id>
    <secondary_id>UH3TR000958</secondary_id>
    <nct_id>NCT02230384</nct_id>
  </id_info>
  <brief_title>Novel Smoking Cessation Drug for Schizophrenia</brief_title>
  <acronym>TRENDS</acronym>
  <official_title>The Development of of A Novel Therapeutic to Aid Tobacco Smoking Cessation in Persons With Schizophrenia or Schizoaffective Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>K.N. Roy Chengappa</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators will evaluate effects of a novel drug that improves nicotinergic receptor&#xD;
      function vs. placebo on short-term smoking abstinence in smokers with schizophrenia who have&#xD;
      a high interest in quitting. The investigators predict that the novel drug will increase days&#xD;
      of abstinence, compared with placebo, identifying potential evidence of efficacy for smoking&#xD;
      cessation in smokers with schizophrenia.&#xD;
&#xD;
      The investigators will also assess if this new drug decreases nicotine withdrawal, craving,&#xD;
      and cognitive impairment during early abstinence, as well as evaluate adverse effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective:&#xD;
&#xD;
      This is a Proof of Concept study planned over nearly 2 years to determine the potential&#xD;
      efficacy of a novel drug for smokers with schizophrenia.&#xD;
&#xD;
      This study will assess 60 smokers with a diagnosis of either schizophrenia or schizoaffective&#xD;
      disorder with high quit interest on their ability to quit during a week-long attempt to&#xD;
      abstain while receiving a novel drug vs. placebo, using a within-subjects cross-over design.&#xD;
&#xD;
      Research Plan:&#xD;
&#xD;
      Active drug or placebo will be provided to participants in double-blind fashion.&#xD;
&#xD;
      Study participation will last 6 weeks after subjects enter the study following the screening&#xD;
      and physical exam sessions (about 8 weeks total). Participants will engage in two identical&#xD;
      study phases, each involving visits over 3 weeks and varying only in whether active drug or&#xD;
      placebo is administered. The 3 weeks will involve: baseline visits, dose run-up (week 2), and&#xD;
      week 3 (for abstinence assessments). The first week of each period will be a baseline week in&#xD;
      which they smoke normally without any medication. During week 2, subjects will begin the dose&#xD;
      run-up of active drug or placebo, increasing over 4 days from 1 tablet of 50 mg once daily to&#xD;
      100 mg b.i.d. (two 50 mg tablets twice/day), which will continue through the second and third&#xD;
      weeks. Active drug or placebo will be administered in counter-balanced order in a cross-over&#xD;
      design. During week 3, subjects will be instructed to try to abstain on each day, i.e.&#xD;
      Mon-Friday. Most visits will last 60 mins and involve psychiatric assessments (including&#xD;
      psychopathology and neurological and other side effects) ratings, providing an expired breath&#xD;
      carbon monoxide (CO) measure that assesses smoking exposure in the past 24 hrs, as well as&#xD;
      completing brief self-report measures of craving, withdrawal, and mood. On week 3 of each&#xD;
      phase, one visit will involve cognitive testing. On Fri of week 3, subjects will discontinue&#xD;
      all medication and resume ad lib smoking prior to the next study period, involving the same&#xD;
      3-week procedure (but with the other medication condition): baseline, dose run-up, full dose&#xD;
      administration plus abstinence assessment. Note that active medication will be taken during&#xD;
      only one period, with placebo taken during the other period. Pill counts will be used to&#xD;
      measure adherence.&#xD;
&#xD;
      Primary and secondary dependent measures are described separately in this report.&#xD;
&#xD;
      Psychopathology will be assessed using standard rating scales to evaluate psychoses and&#xD;
      general psychopathology and severity of illness ratings, and suicide rating scales. These and&#xD;
      clinical impressions of patients in the study will assist in monitoring for stability or&#xD;
      worsening of psychoses or suicidal behavior and/or the need to exit patients from the study.&#xD;
&#xD;
      Laboratory and EKG monitoring at the beginning and end of the study will also be part of the&#xD;
      subject safety procedures.&#xD;
&#xD;
      Patients will be offered their choice of one of the FDA approved smoking cessation agents,&#xD;
      i.e. nicotine replacement therapy, bupropion or varenicline for a 3-month period upon&#xD;
      completion of the study. If patients decline open-label smoking cessation participation, they&#xD;
      will be requested to come in for one post-study visit, 14 ± 4 days later. At the first&#xD;
      post-study visit, if there are no adverse events, their participation will end.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      The novel drug or placebo will be administered double-blind in counter-balanced order in a&#xD;
      cross-over design. This is not a clinical trial that assesses long term smoking cessation but&#xD;
      a within-subjects comparison of the short-term effects of this drug on abstinence and&#xD;
      abstinence symptoms over a week-long period, relative to placebo.&#xD;
&#xD;
      Significance:&#xD;
&#xD;
      This study addresses an important question of whether the novel drug shows potential efficacy&#xD;
      for smoking cessation, relative to placebo, in smokers with schizophrenia. This procedure&#xD;
      could have enormous implications for accelerating the development of this medication and&#xD;
      similar compounds to help people quit smoking by increasing the efficiency of early&#xD;
      medication evaluation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">March 9, 2017</completion_date>
  <primary_completion_date type="Actual">December 16, 2016</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quit Status</measure>
    <time_frame>Daily - Mon-Fri during the quit week in each phase</time_frame>
    <description>Complete abstinence from smoking for 24 hr, assessed daily from Mon-Fri for just one week. This same Mon-Fri procedure for one week (only) is done for both drug phases (Number of days abstinent per each quit week)&#xD;
Numbers reported are collapsed across medication conditions for each medication order.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Withdrawal When Quit</measure>
    <time_frame>during each quit week</time_frame>
    <description>Severity of withdrawal symptoms will be assessed with standard self-report measures each day during the quit week only of each phase. Data will be analysed when quit criteria were met. Scale used was the Minnesota Nicotine Withdrawal Scale (MNWS), ranging from 0 to 100, with higher scores indicating greater levels of withdrawal symptoms. The MNWS was completed 5 times for each participant during the quit week of each phase. The mean score was used to aggregate across visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Functions</measure>
    <time_frame>Assessed at the end of both treatment phases, i.e., at the end of 3 and 6 weeks.</time_frame>
    <description>Performance on standardized cognitive tasks (Continuous Performance Task) to determine potential mechanisms of drug efficacy when CO &lt; 10 smoking reduction criteria was met for both sessions. The Continuous Performance Test provides assesses sustained attention in milliseconds.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monitoring of Psychiatric Symptoms Including Psychopathology</measure>
    <time_frame>Once at every scheduled visit</time_frame>
    <description>Psychiatric symptoms using Positive and Negative Syndrome Scale (PANSS) will be conducted at each visit in each 3 week phase of the study&#xD;
PANSS - Positive and Negative Syndrome Scale. Min value 30, Max value 210, higher scores are worse outcome.&#xD;
The mean score was used to aggregate across visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants That Met Criteria for Treatment Emergent Suicidal Ideation or Behavior</measure>
    <time_frame>Every visit up to six weeks. It is only significant when there is a positive response &quot;Yes&quot;</time_frame>
    <description>CSSRS: Columbia Suicide Severity rating Scale. The scale assesses treatment emergent suicidal ideation and/or behavior categorically as a YES/NO response (no min/max score). &quot;No&quot; responses indicate ideation/behaviors did not emerge &quot;Yes&quot; responses indicate there were ideation or behaviors We are reporting the number of participants that met criteria for suicidal ideation or behavior, based on their CSSRS assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants That Had Treatment Emergent Clinically Significant Abnormal Lab Results</measure>
    <time_frame>Weeks 0, 2, 3, 5, 6</time_frame>
    <description>Routine safety labs (included liver and renal labs) were done at baseline, Visit 9, and Visit 18 to determine whether there were treatment emergent clinically significant changes in any of the laboratory parameters. (no subject with abnormal labs at baseline were enrolled in the study) In addition, liver and renal labs were drawn at Visit 4 and Visit 13 to assess for treatment emergent, clinically significant abnormal liver and renal functions.&#xD;
The reported results in the data table below show the number of subjects that had treatment emergent clinically significant abnormal lab results at any of the time points.&#xD;
If labs were not within the normal range, they were reviewed by the physician investigators to determine whether they were clinically significant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Participants Who Had Treatment Emergent Clinically Significant EKG Results</measure>
    <time_frame>Baseline (Week 0) and end of study (week 6)</time_frame>
    <description>EKG measures were done at the screening visit and at the end of study to determine whether there were treatment emergent clinically significant changes in the EKG parameters.&#xD;
No subjects with abnormal EKGs at baseline were enrolled in the study The data table below shows the number of subjects with clinically significant abnormal EKG results at the end of the study.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Smoking Cessation</condition>
  <arm_group>
    <arm_group_label>Active JNJ 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>Active JNJ 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>Active JNJ Drug</arm_group_label>
    <arm_group_label>Placebo Pill</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: List the specific criteria for inclusion of potential subjects.&#xD;
&#xD;
          -  Men or women of any race, ages 18 to 65 years, (≥18 years, ≤ 66 years)&#xD;
&#xD;
          -  Willing to provide written informed consent&#xD;
&#xD;
          -  MINI (Sheehan et al 1998, 2008) chart and/or clinician consensus affirmed DSM IV TR or&#xD;
             (DSM -V) diagnoses of schizophrenia or schizoaffective disorder.&#xD;
&#xD;
          -  Patients whose PANSS total scores have been stable for ≥ 4 weeks (clinician and/or&#xD;
             subject affirmed) and at ≤ 70&#xD;
&#xD;
          -  No recent ( ≤ 3months) hospitalization, aggression, or suicidal attempts&#xD;
&#xD;
          -  Stable doses of antipsychotic medication, ≥ 4 weeks&#xD;
&#xD;
        Smoking Inclusion Criteria:&#xD;
&#xD;
          -  Smoke ≥ 5 cigarettes/day&#xD;
&#xD;
          -  Smoking cigarettes ≥ 1 year&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Smoking/Nicotine Exclusions:&#xD;
&#xD;
          -  Use of smokeless tobacco or snuff or chewing tobacco&#xD;
&#xD;
          -  Use of e-cigarettes, or any non-tobacco nicotine products (e.g. nicotine gum,&#xD;
             lozenges, patch, etc.)&#xD;
&#xD;
          -  Current enrollment or plans to enroll in another smoking cessation program. (Bupropion&#xD;
             use for depression will be assessed on a case by case basis)&#xD;
&#xD;
        Alcohol/Illicit Substance Exclusion Criteria:&#xD;
&#xD;
          -  Recent alcohol or substance dependence (≤ 3 months)&#xD;
&#xD;
          -  Current alcohol consumption that exceeds 15 standard drinks/week or greater than 2&#xD;
             standard drinks daily&#xD;
&#xD;
        Medical Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant, planning a pregnancy, or lactating; all female participants&#xD;
             shall undergo a pregnancy test at screening and will be excluded if positive.&#xD;
&#xD;
          -  Serious or unstable medical disorder within the past 3 months (assessed by the&#xD;
             investigators)&#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) defined as serum glutamate oxaloacetate&#xD;
             transaminase (SGOT) (AST) or serum glutamate pyruvate transaminase (SGPT) (ALT) or&#xD;
             alkaline phosphatase greater than 1x the upper limit of normal, or bilirubin 1x the&#xD;
             upper limit of normal&#xD;
&#xD;
          -  Evidence of kidney failure defined as: Serum creatinine &gt; 1.8 mg/dl for males and 1.6&#xD;
             mg/dl for females.&#xD;
&#xD;
          -  Any subject with a history of hematological cancers examples: leukemia, lymphoma etc.&#xD;
             will be excluded.&#xD;
&#xD;
          -  Any clinically significant hematological laboratory abnormality (chronic low-grade&#xD;
             laboratory values just above or below the reference range that are without clinical&#xD;
             significance will be permitted) will be grounds for exclusion.&#xD;
&#xD;
        Medication Exclusion Criteria:&#xD;
&#xD;
          -  Current use or recent discontinuation (within last 14-days) of the following&#xD;
             medications: any form of smoking cessation medication (Bupropion except when used for&#xD;
             Depressive Disorders on a case by case basis, Varenicline, NRT); and (b)&#xD;
             opiate-containing medications for chronic pain. Potent CYP 3A4 inhibitors will be&#xD;
             reviewed for exclusion, see below.&#xD;
&#xD;
          -  In view of novel drug being a moderate CYP3A4 inhibitor, any subjects receiving the&#xD;
             following narrow therapeutic index CYP3A4 substrates will be excluded: Alfentanil,&#xD;
             astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, fentanyl,&#xD;
             pimozide, quinidine, sirolimus, tacrolimus, terfenadine.&#xD;
&#xD;
          -  In view of the impact of clozapine on smoking cessation, patients receiving clozapine&#xD;
             will be excluded.&#xD;
&#xD;
          -  Stable medical conditions examples: hypertension, diabetes, dyslipidemia etc that are&#xD;
             treated and ongoing and patients are not receiving the exclusionary drugs noted above&#xD;
             will be considered for inclusion on a case by case basis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>66 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>K.N. Roy Chengappa, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Western Psychiatric Institute and Clinic - UPMC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Western Psychiatric Institute and Clinic and affilated sites</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>March 2019</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>August 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <results_first_submitted>January 5, 2018</results_first_submitted>
  <results_first_submitted_qc>January 5, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">January 30, 2018</results_first_posted>
  <last_update_submitted>March 21, 2019</last_update_submitted>
  <last_update_submitted_qc>March 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>K.N. Roy Chengappa</investigator_full_name>
    <investigator_title>Professor of Psychiatry</investigator_title>
  </responsible_party>
  <keyword>Attempt at Smoking Cessation</keyword>
  <keyword>Schizophrenia or Schizoaffective disorder</keyword>
  <keyword>Novel nicotinergic drug</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Active JNJ Drug Then Placebo</title>
          <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.&#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>Placebo Pill Then Active JNJ Drug</title>
          <description>Placebo pill used for one week quit attempt, as part of crossover design.&#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>Phase 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </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>Physician Decision</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>
          <title>Phase 1 Wash Out</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="31"/>
              </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>Phase 2 - Switch</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <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>
              <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>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Phase 2 Wash Out</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="30"/>
              </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>Active JNJ Drug Then Placebo</title>
          <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.&#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>Placebo Pill Then Active JNJ Drug</title>
          <description>Placebo pill used for one week quit attempt, as part of crossover design.&#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="30"/>
            <count group_id="B2" value="32"/>
            <count group_id="B3" value="62"/>
          </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="30"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="62"/>
                  </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>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="46.06" spread="11.31"/>
                    <measurement group_id="B2" value="46.31" spread="10.97"/>
                    <measurement group_id="B3" value="46.19" spread="11.04"/>
                  </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="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="62"/>
                  </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, assessed daily from Mon-Fri for just one week. This same Mon-Fri procedure for one week (only) is done for both drug phases (Number of days abstinent per each quit week)&#xD;
Numbers reported are collapsed across medication conditions for each medication order.</description>
        <time_frame>Daily - Mon-Fri during the quit week in each phase</time_frame>
        <population>All participants who completed Phase 1 and Phase 2 of the of the study were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Active JNJ Drug</title>
            <description>Period during which participants received Active JNJ Drug: 200 mg/day (100 mg b.i.d.)</description>
          </group>
          <group group_id="O2">
            <title>Placebo Pill</title>
            <description>Period during which Participants received Placebo pill: 200 mg/day (100 mg b.i.d.)</description>
          </group>
        </group_list>
        <measure>
          <title>Quit Status</title>
          <description>Complete abstinence from smoking for 24 hr, assessed daily from Mon-Fri for just one week. This same Mon-Fri procedure for one week (only) is done for both drug phases (Number of days abstinent per each quit week)&#xD;
Numbers reported are collapsed across medication conditions for each medication order.</description>
          <population>All participants who completed Phase 1 and Phase 2 of the of the study were included in the analysis.</population>
          <units>days abstinent</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.46" spread="0.151"/>
                    <measurement group_id="O2" value="0.54" spread="0.173"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Withdrawal When Quit</title>
        <description>Severity of withdrawal symptoms will be assessed with standard self-report measures each day during the quit week only of each phase. Data will be analysed when quit criteria were met. Scale used was the Minnesota Nicotine Withdrawal Scale (MNWS), ranging from 0 to 100, with higher scores indicating greater levels of withdrawal symptoms. The MNWS was completed 5 times for each participant during the quit week of each phase. The mean score was used to aggregate across visits.</description>
        <time_frame>during each quit week</time_frame>
        <population>Participants who met CO &lt; 5 ppm quit criterion.</population>
        <group_list>
          <group group_id="O1">
            <title>JNJ Drug</title>
            <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.&#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</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo pill used for one week quit attempt, as part of crossover design.&#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>Withdrawal When Quit</title>
          <description>Severity of withdrawal symptoms will be assessed with standard self-report measures each day during the quit week only of each phase. Data will be analysed when quit criteria were met. Scale used was the Minnesota Nicotine Withdrawal Scale (MNWS), ranging from 0 to 100, with higher scores indicating greater levels of withdrawal symptoms. The MNWS was completed 5 times for each participant during the quit week of each phase. The mean score was used to aggregate across visits.</description>
          <population>Participants who met CO &lt; 5 ppm quit criterion.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.05" spread="2.86"/>
                    <measurement group_id="O2" value="11.52" spread="1.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cognitive Functions</title>
        <description>Performance on standardized cognitive tasks (Continuous Performance Task) to determine potential mechanisms of drug efficacy when CO &lt; 10 smoking reduction criteria was met for both sessions. The Continuous Performance Test provides assesses sustained attention in milliseconds.</description>
        <time_frame>Assessed at the end of both treatment phases, i.e., at the end of 3 and 6 weeks.</time_frame>
        <population>those who met the CO &lt; 10 smoking reduction criteria at the end of both treatment phases</population>
        <group_list>
          <group group_id="O1">
            <title>JNJ Drug</title>
            <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.&#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</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo pill used for one week quit attempt, as part of crossover design.&#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 Functions</title>
          <description>Performance on standardized cognitive tasks (Continuous Performance Task) to determine potential mechanisms of drug efficacy when CO &lt; 10 smoking reduction criteria was met for both sessions. The Continuous Performance Test provides assesses sustained attention in milliseconds.</description>
          <population>those who met the CO &lt; 10 smoking reduction criteria at the end of both treatment phases</population>
          <units>milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Error</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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="519" spread="37"/>
                    <measurement group_id="O2" value="505" spread="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Monitoring of Psychiatric Symptoms Including Psychopathology</title>
        <description>Psychiatric symptoms using Positive and Negative Syndrome Scale (PANSS) will be conducted at each visit in each 3 week phase of the study&#xD;
PANSS - Positive and Negative Syndrome Scale. Min value 30, Max value 210, higher scores are worse outcome.&#xD;
The mean score was used to aggregate across visits.</description>
        <time_frame>Once at every scheduled visit</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active JNJ Drug</title>
            <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.&#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</description>
          </group>
          <group group_id="O2">
            <title>Placebo Pill</title>
            <description>Placebo pill used for one week quit attempt, as part of crossover design.&#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>Monitoring of Psychiatric Symptoms Including Psychopathology</title>
          <description>Psychiatric symptoms using Positive and Negative Syndrome Scale (PANSS) will be conducted at each visit in each 3 week phase of the study&#xD;
PANSS - Positive and Negative Syndrome Scale. Min value 30, Max value 210, higher scores are worse outcome.&#xD;
The mean score was used to aggregate across visits.</description>
          <units>score 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="56"/>
                <count group_id="O2" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.23" spread="7.79"/>
                    <measurement group_id="O2" value="42.26" spread="7.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants That Met Criteria for Treatment Emergent Suicidal Ideation or Behavior</title>
        <description>CSSRS: Columbia Suicide Severity rating Scale. The scale assesses treatment emergent suicidal ideation and/or behavior categorically as a YES/NO response (no min/max score). &quot;No&quot; responses indicate ideation/behaviors did not emerge &quot;Yes&quot; responses indicate there were ideation or behaviors We are reporting the number of participants that met criteria for suicidal ideation or behavior, based on their CSSRS assessment</description>
        <time_frame>Every visit up to six weeks. It is only significant when there is a positive response &quot;Yes&quot;</time_frame>
        <group_list>
          <group group_id="O1">
            <title>JNJ Drug</title>
            <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.&#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>Placebo</title>
            <description>Placebo pill used for one week quit attempt, as part of crossover design.&#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>Number of Participants That Met Criteria for Treatment Emergent Suicidal Ideation or Behavior</title>
          <description>CSSRS: Columbia Suicide Severity rating Scale. The scale assesses treatment emergent suicidal ideation and/or behavior categorically as a YES/NO response (no min/max score). &quot;No&quot; responses indicate ideation/behaviors did not emerge &quot;Yes&quot; responses indicate there were ideation or behaviors We are reporting the number of participants that met criteria for suicidal ideation or behavior, based on their CSSRS assessment</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="56"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants That Had Treatment Emergent Clinically Significant Abnormal Lab Results</title>
        <description>Routine safety labs (included liver and renal labs) were done at baseline, Visit 9, and Visit 18 to determine whether there were treatment emergent clinically significant changes in any of the laboratory parameters. (no subject with abnormal labs at baseline were enrolled in the study) In addition, liver and renal labs were drawn at Visit 4 and Visit 13 to assess for treatment emergent, clinically significant abnormal liver and renal functions.&#xD;
The reported results in the data table below show the number of subjects that had treatment emergent clinically significant abnormal lab results at any of the time points.&#xD;
If labs were not within the normal range, they were reviewed by the physician investigators to determine whether they were clinically significant.</description>
        <time_frame>Weeks 0, 2, 3, 5, 6</time_frame>
        <population>Intent to treat population (all participants who received at least one dose of intervention)</population>
        <group_list>
          <group group_id="O1">
            <title>Active JNJ Drug Then Placebo</title>
            <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.&#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>Placebo Pill Then Active JNJ Drug</title>
            <description>Placebo pill used for one week quit attempt, as part of crossover design.&#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>Number of Participants That Had Treatment Emergent Clinically Significant Abnormal Lab Results</title>
          <description>Routine safety labs (included liver and renal labs) were done at baseline, Visit 9, and Visit 18 to determine whether there were treatment emergent clinically significant changes in any of the laboratory parameters. (no subject with abnormal labs at baseline were enrolled in the study) In addition, liver and renal labs were drawn at Visit 4 and Visit 13 to assess for treatment emergent, clinically significant abnormal liver and renal functions.&#xD;
The reported results in the data table below show the number of subjects that had treatment emergent clinically significant abnormal lab results at any of the time points.&#xD;
If labs were not within the normal range, they were reviewed by the physician investigators to determine whether they were clinically significant.</description>
          <population>Intent to treat population (all participants who received at least one dose of intervention)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Liver and Renal Labs Only Wk 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Routine Labs (including Liver and Renal) Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Liver and Renal Labs Only Wk 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Routine Labs (including Liver and Renal) Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Participants Who Had Treatment Emergent Clinically Significant EKG Results</title>
        <description>EKG measures were done at the screening visit and at the end of study to determine whether there were treatment emergent clinically significant changes in the EKG parameters.&#xD;
No subjects with abnormal EKGs at baseline were enrolled in the study The data table below shows the number of subjects with clinically significant abnormal EKG results at the end of the study.</description>
        <time_frame>Baseline (Week 0) and end of study (week 6)</time_frame>
        <population>Intent to treat population (all participants who received at least on dose of intervention)</population>
        <group_list>
          <group group_id="O1">
            <title>Active JNJ Drug Then Placebo</title>
            <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.&#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>Placebo Pill Then Active JNJ Drug</title>
            <description>Placebo pill used for one week quit attempt, as part of crossover design.&#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>The Number of Participants Who Had Treatment Emergent Clinically Significant EKG Results</title>
          <description>EKG measures were done at the screening visit and at the end of study to determine whether there were treatment emergent clinically significant changes in the EKG parameters.&#xD;
No subjects with abnormal EKGs at baseline were enrolled in the study The data table below shows the number of subjects with clinically significant abnormal EKG results at the end of the study.</description>
          <population>Intent to treat population (all participants who received at least on dose of intervention)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 weeks</time_frame>
      <desc>Cross-Over study, all subjects received both JNJ and Placebo. Tables below reflect whether the event occurred during the receipt of JNJ or during the receipt of placebo.&#xD;
62 subjects were randomized, of whom 7 did not complete the study. Of those 7, 3 were exposed to both JNJ and Placebo, 1 was exposed to the JNJ condition only, 2 were exposed to the placebo condition only and 1 was not exposed to either condition. Thus 60 subjects were exposed to JNJ and 61 subjects were exposed to placebo.</desc>
      <group_list>
        <group group_id="E1">
          <title>JNJ Drug</title>
          <description>Period during which participants received Active JNJ Drug: 200 mg/day (100 mg b.i.d.)</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Period during which Participants received Placebo pill: 200 mg/day (100 mg b.i.d.)</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="60"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="61"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>acute diastolic congestive heart failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>persistent vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="61"/>
              </event>
              <event>
                <sub_title>abdominal pain</sub_title>
                <description>This event occurred during the wash out period following having the active JNJ drug</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="60"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>aspiration/pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="60"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>vaginal bleeding</sub_title>
                <description>This event occurred during the wash out period following having the active JNJ drug</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="60"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="30" subjects_at_risk="60"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="60"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="60"/>
                <counts group_id="E2" events="10" subjects_affected="8" subjects_at_risk="61"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="60"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="60"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle pain/soreness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="60"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="60"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="61"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="60"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cold/nasal congestion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="60"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="61"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="60"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="61"/>
              </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>
    <point_of_contact>
      <name_or_title>K.N. Roy Chengappa, MD / Principal Investigator</name_or_title>
      <organization>University of Pittsburgh</organization>
      <phone>412-246-5006 ext 412</phone>
      <email>chengappakn@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/NCT02230384
org study id: PRO14060338
secondary id: UH3TR000958
nct id: NCT02230384
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The investigators will evaluate effects of a novel drug that improves nicotinergic receptor
      function vs. placebo on short-term smoking abstinence in smokers with schizophrenia who have
      a high interest in quitting. The investigators predict that the novel drug will increase days
      of abstinence, compared with placebo, identifying potential evidence of efficacy for smoking
      cessation in smokers with schizophrenia.

      The investigators will also assess if this new drug decreases nicotine withdrawal, craving,
      and cognitive impairment during early abstinence, as well as evaluate adverse effects.
Objective:

      This is a Proof of Concept study planned over nearly 2 years to determine the potential
      efficacy of a novel drug for smokers with schizophrenia.

      This study will assess 60 smokers with a diagnosis of either schizophrenia or schizoaffective
      disorder with high quit interest on their ability to quit during a week-long attempt to
      abstain while receiving a novel drug vs. placebo, using a within-subjects cross-over design.

      Research Plan:

      Active drug or placebo will be provided to participants in double-blind fashion.

      Study participation will last 6 weeks after subjects enter the study following the screening
      and physical exam sessions (about 8 weeks total). Participants will engage in two identical
      study phases, each involving visits over 3 weeks and varying only in whether active drug or
      placebo is administered. The 3 weeks will involve: baseline visits, dose run-up (week 2), and
      week 3 (for abstinence assessments). The first week of each period will be a baseline week in
      which they smoke normally without any medication. During week 2, subjects will begin the dose
      run-up of active drug or placebo, increasing over 4 days from 1 tablet of 50 mg once daily to
      100 mg b.i.d. (two 50 mg tablets twice/day), which will continue through the second and third
      weeks. Active drug or placebo will be administered in counter-balanced order in a cross-over
      design. During week 3, subjects will be instructed to try to abstain on each day, i.e.
      Mon-Friday. Most visits will last 60 mins and involve psychiatric assessments (including
      psychopathology and neurological and other side effects) ratings, providing an expired breath
      carbon monoxide (CO) measure that assesses smoking exposure in the past 24 hrs, as well as
      completing brief self-report measures of craving, withdrawal, and mood. On week 3 of each
      phase, one visit will involve cognitive testing. On Fri of week 3, subjects will discontinue
      all medication and resume ad lib smoking prior to the next study period, involving the same
      3-week procedure (but with the other medication condition): baseline, dose run-up, full dose
      administration plus abstinence assessment. Note that active medication will be taken during
      only one period, with placebo taken during the other period. Pill counts will be used to
      measure adherence.

      Primary and secondary dependent measures are described separately in this report.

      Psychopathology will be assessed using standard rating scales to evaluate psychoses and
      general psychopathology and severity of illness ratings, and suicide rating scales. These and
      clinical impressions of patients in the study will assist in monitoring for stability or
      worsening of psychoses or suicidal behavior and/or the need to exit patients from the study.

      Laboratory and EKG monitoring at the beginning and end of the study will also be part of the
      subject safety procedures.

      Patients will be offered their choice of one of the FDA approved smoking cessation agents,
      i.e. nicotine replacement therapy, bupropion or varenicline for a 3-month period upon
      completion of the study. If patients decline open-label smoking cessation participation, they
      will be requested to come in for one post-study visit, 14 ± 4 days later. At the first
      post-study visit, if there are no adverse events, their participation will end.

      Methods:

      The novel drug or placebo will be administered double-blind in counter-balanced order in a
      cross-over design. This is not a clinical trial that assesses long term smoking cessation but
      a within-subjects comparison of the short-term effects of this drug on abstinence and
      abstinence symptoms over a week-long period, relative to placebo.

      Significance:

      This study addresses an important question of whether the novel drug shows potential efficacy
      for smoking cessation, relative to placebo, in smokers with schizophrenia. This procedure
      could have enormous implications for accelerating the development of this medication and
      similar compounds to help people quit smoking by increasing the efficiency of early
      medication evaluation.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Quit Status
time frame: Daily - Mon-Fri during the quit week in each phase
description: Complete abstinence from smoking for 24 hr, assessed daily from Mon-Fri for just one week. This same Mon-Fri procedure for one week (only) is done for both drug phases (Number of days abstinent per each quit week)
Numbers reported are collapsed across medication conditions for each medication order.
measure: Withdrawal When Quit
time frame: during each quit week
description: Severity of withdrawal symptoms will be assessed with standard self-report measures each day during the quit week only of each phase. Data will be analysed when quit criteria were met. Scale used was the Minnesota Nicotine Withdrawal Scale (MNWS), ranging from 0 to 100, with higher scores indicating greater levels of withdrawal symptoms. The MNWS was completed 5 times for each participant during the quit week of each phase. The mean score was used to aggregate across visits.
measure: Cognitive Functions
time frame: Assessed at the end of both treatment phases, i.e., at the end of 3 and 6 weeks.
description: Performance on standardized cognitive tasks (Continuous Performance Task) to determine potential mechanisms of drug efficacy when CO < 10 smoking reduction criteria was met for both sessions. The Continuous Performance Test provides assesses sustained attention in milliseconds.
measure: Monitoring of Psychiatric Symptoms Including Psychopathology
time frame: Once at every scheduled visit
description: Psychiatric symptoms using Positive and Negative Syndrome Scale (PANSS) will be conducted at each visit in each 3 week phase of the study
PANSS - Positive and Negative Syndrome Scale. Min value 30, Max value 210, higher scores are worse outcome.
The mean score was used to aggregate across visits.
measure: Number of Participants That Met Criteria for Treatment Emergent Suicidal Ideation or Behavior
time frame: Every visit up to six weeks. It is only significant when there is a positive response "Yes"
description: CSSRS: Columbia Suicide Severity rating Scale. The scale assesses treatment emergent suicidal ideation and/or behavior categorically as a YES/NO response (no min/max score). "No" responses indicate ideation/behaviors did not emerge "Yes" responses indicate there were ideation or behaviors We are reporting the number of participants that met criteria for suicidal ideation or behavior, based on their CSSRS assessment
measure: Number of Participants That Had Treatment Emergent Clinically Significant Abnormal Lab Results
time frame: Weeks 0, 2, 3, 5, 6
description: Routine safety labs (included liver and renal labs) were done at baseline, Visit 9, and Visit 18 to determine whether there were treatment emergent clinically significant changes in any of the laboratory parameters. (no subject with abnormal labs at baseline were enrolled in the study) In addition, liver and renal labs were drawn at Visit 4 and Visit 13 to assess for treatment emergent, clinically significant abnormal liver and renal functions.
The reported results in the data table below show the number of subjects that had treatment emergent clinically significant abnormal lab results at any of the time points.
If labs were not within the normal range, they were reviewed by the physician investigators to determine whether they were clinically significant.
measure: The Number of Participants Who Had Treatment Emergent Clinically Significant EKG Results
time frame: Baseline (Week 0) and end of study (week 6)
description: EKG measures were done at the screening visit and at the end of study to determine whether there were treatment emergent clinically significant changes in the EKG parameters.
No subjects with abnormal EKGs at baseline were enrolled in the study The data table below shows the number of subjects with clinically significant abnormal EKG results at the end of the study.
arm group label: Active JNJ 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: Active JNJ 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: Active JNJ Drug
arm group label: Placebo Pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: 66 Years
healthy volunteers: No
last name: K.N. Roy Chengappa, MD
role: Principal Investigator
affiliation: Western Psychiatric Institute and Clinic - UPMC
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: K.N. Roy Chengappa
investigator title: Professor of Psychiatry
mesh term: Schizophrenia
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 