<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/NCT01680887</url>
  </required_header>
  <id_info>
    <org_study_id>814643</org_study_id>
    <nct_id>NCT01680887</nct_id>
  </id_info>
  <brief_title>A Phase II Trial of Varenicline for the Treatment of Cocaine Dependence</brief_title>
  <official_title>A Phase II, Randomized, Double-Blind Trial of Varenicline for the Treatment of Cocaine Dependence</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a double-blind placebo-controlled clinical trial (n = 156) of varenicline for the&#xD;
      treatment of cocaine dependence that utilizes contingency management to promote treatment&#xD;
      attendance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Varenicline is a medication approved for the treatment of Tobacco Use Disorder.&#xD;
      It is a partial agonist at α2β4 nicotinic acetyl choline receptors and a full agonist at α7&#xD;
      nicotinic acetyl choline receptors. By its effects on cholinergic activity at α7 and α2β4&#xD;
      receptors, varenicline may reduce dopaminergic and glutamatergic activity in the midbrain,&#xD;
      and reduce symptoms of Cocaine Use Disorder. A preliminary trial of varenicline in human&#xD;
      cocaine users suggested that varenicline treatment was associated with reductions in cocaine&#xD;
      use. The current trial was intended to confirm these promising preliminary results.&#xD;
&#xD;
      Methods: This was a 12-week, double blind, placebo controlled parallel group clinical trial&#xD;
      involving 156 DSM IV cocaine dependent subjects. Subjects received 2 mg of varenicline or&#xD;
      identical placebo each day along with weekly individual cognitive behavioral relapse&#xD;
      prevention psychotherapy. The primary outcome measure was cocaine use measured by by thrice&#xD;
      weekly urine drug screens. Additional outcome measures included cocaine withdrawal symptoms&#xD;
      measured by the Cocaine Selective Severity Assessment (CSSA) End of study cocaine abstinence&#xD;
      was analyzed using a Chi-square test.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">June 2019</completion_date>
  <primary_completion_date type="Actual">January 2018</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Who Report no Cocaine Use and Have no Cocaine Positive Urine Drug Screens in the Chantix Group Versus the Placebo Group Comparator During the Last Three Weeks of the Trial</measure>
    <time_frame>weeks 11,12,13 of the trial</time_frame>
    <description>Number of subjects with cocaine abstinence as measured through three-times-weekly urine benzoylecgonine (BE) levels in urine drug screen (UDS) and self-reports of use from the Time Line Follow Back. UDS results and TLFB reports combined to yield weekly use/no-use indicators for each week of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Average Weekly Cocaine Craving Scores Varenicline Group Versus the Placebo Group Comparator</measure>
    <time_frame>Once per week in weeks 2 through 13</time_frame>
    <description>As measured by average weekly scores for cocaine craving on the brief substance craving scale combining cocaine craving frequency, intensity and duration. Minimum value 0 maximum value 12 higher scores indicate worse craving.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">156</enrollment>
  <condition>Cocaine Dependence</condition>
  <arm_group>
    <arm_group_label>Varenicline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral 1.0 mg BID.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral 1.0 mg BID.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Varenicline</intervention_name>
    <arm_group_label>Varenicline</arm_group_label>
    <other_name>Chantix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females, 18 to 65 years old.&#xD;
&#xD;
          2. Meets DSM-IV criteria for Cocaine Dependence, as determined by the Structured Clinical&#xD;
             Interview for DSM-IV (SCID).&#xD;
&#xD;
          3. Live within a commutable distance of the Treatment Research Center (TRC) at the&#xD;
             Penn/VA Center for Studies of Addiction, University of Pennsylvania. We define this to&#xD;
             be a distance within the service area of Septa, within an hour drive, or a distance&#xD;
             that both the patient and Principal Investigator (PI) find acceptable.&#xD;
&#xD;
          4. Understands and signs the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine,&#xD;
             alcohol, or nicotine dependence, as determined by the SCID.&#xD;
&#xD;
          2. Subject is, in the investigator's opinion, at risk of requiring medical detoxification&#xD;
             for alcohol dependence during the study.&#xD;
&#xD;
          3. Concomitant treatment with psychotropic medications.&#xD;
&#xD;
          4. Current gambling problems. This will be assessed by the patient's self-report.&#xD;
&#xD;
          5. Patients mandated to treatment based upon a legal decision or as a condition of&#xD;
             employment who will use participation in this study to fulfill to their court mandated&#xD;
             treatment requirement.This will be assessed by the patient's self-report.&#xD;
&#xD;
          6. Current severe psychiatric symptoms, e.g., psychosis, dementia, suicidal or homicidal&#xD;
             ideation, mania or depression requiring antidepressant therapy in the opinion of the&#xD;
             Principal Investigator (PI).&#xD;
&#xD;
          7. Use of any investigational medication within the past 30 days.&#xD;
&#xD;
          8. Subject has serious heart, lung, kidney, immune system, GI tract (ulcerative colitis,&#xD;
             regional enteritis, or gastrointestinal bleeding) disease.&#xD;
&#xD;
          9. Current use of naltrexone, disulfiram, modafinil, stimulants, haloperidol,&#xD;
             benzodiazepines or anticonvulsants.&#xD;
&#xD;
         10. Known hypersensitivity to varenicline.&#xD;
&#xD;
         11. Patients with known AIDS or other serious illnesses that may require hospitalization&#xD;
             during the study.&#xD;
&#xD;
         12. Female subjects who are pregnant or lactating, or female subjects of child-bearing&#xD;
             potential who are not using acceptable methods of birth control. Acceptable methods of&#xD;
             birth control include:&#xD;
&#xD;
               1. barrier (diaphragm or condom) with spermicide&#xD;
&#xD;
               2. intrauterine progesterone contraceptive system&#xD;
&#xD;
               3. levonorgestrel implant&#xD;
&#xD;
               4. medroxyprogesterone acetate contraceptive injection&#xD;
&#xD;
               5. oral contraceptives&#xD;
&#xD;
               6. tubal ligation.&#xD;
&#xD;
         13. Patients with impaired renal function as indicated by corrected creatinine clearance&#xD;
             below 60 ml/min as determined by the modified Cockcroft equation (CDC, 1986).&#xD;
&#xD;
         14. Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits&#xD;
             that are clinically unacceptable to the Medical Director. EKG 1st degree heart block,&#xD;
             sinus tachycardia, left axis deviation, and nonspecific ST or T wave changes are&#xD;
             allowed; liver function tests [LFTs] &lt;5 x ULN are acceptable).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kyle M Kampman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pennsylvania Treatment Research Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.med.upenn.edu/csa/</url>
    <description>University of Pennsylvania Center for Studies of Addictions</description>
  </link>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>August 28, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <results_first_submitted>June 24, 2019</results_first_submitted>
  <results_first_submitted_qc>July 18, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 6, 2019</results_first_posted>
  <last_update_submitted>July 18, 2019</last_update_submitted>
  <last_update_submitted_qc>July 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cocaine dependence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cocaine-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Varenicline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>January 28, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT01680887/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Varenicline</title>
          <description>Oral 1.0 mg BID.&#xD;
Varenicline</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Oral 1.0 mg BID.&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
                <participants group_id="P2" count="76"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Varenicline</title>
          <description>Oral 1.0 mg BID.&#xD;
Varenicline</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Oral 1.0 mg BID.&#xD;
Placebo</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="80"/>
            <count group_id="B2" value="76"/>
            <count group_id="B3" value="156"/>
          </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="80"/>
                    <measurement group_id="B2" value="75"/>
                    <measurement group_id="B3" value="155"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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="18"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="62"/>
                    <measurement group_id="B2" value="60"/>
                    <measurement group_id="B3" value="122"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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>Asian</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>Native Hawaiian or Other Pacific Islander</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>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="68"/>
                    <measurement group_id="B2" value="68"/>
                    <measurement group_id="B3" value="136"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>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="80"/>
                    <measurement group_id="B2" value="76"/>
                    <measurement group_id="B3" value="156"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Report no Cocaine Use and Have no Cocaine Positive Urine Drug Screens in the Chantix Group Versus the Placebo Group Comparator During the Last Three Weeks of the Trial</title>
        <description>Number of subjects with cocaine abstinence as measured through three-times-weekly urine benzoylecgonine (BE) levels in urine drug screen (UDS) and self-reports of use from the Time Line Follow Back. UDS results and TLFB reports combined to yield weekly use/no-use indicators for each week of treatment.</description>
        <time_frame>weeks 11,12,13 of the trial</time_frame>
        <population>all subject</population>
        <group_list>
          <group group_id="O1">
            <title>Varenicline</title>
            <description>Oral 1.0 mg BID.&#xD;
Varenicline</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Oral 1.0 mg BID.&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Report no Cocaine Use and Have no Cocaine Positive Urine Drug Screens in the Chantix Group Versus the Placebo Group Comparator During the Last Three Weeks of the Trial</title>
          <description>Number of subjects with cocaine abstinence as measured through three-times-weekly urine benzoylecgonine (BE) levels in urine drug screen (UDS) and self-reports of use from the Time Line Follow Back. UDS results and TLFB reports combined to yield weekly use/no-use indicators for each week of treatment.</description>
          <population>all subject</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="80"/>
                <count group_id="O2" value="76"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.403</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Weekly Cocaine Craving Scores Varenicline Group Versus the Placebo Group Comparator</title>
        <description>As measured by average weekly scores for cocaine craving on the brief substance craving scale combining cocaine craving frequency, intensity and duration. Minimum value 0 maximum value 12 higher scores indicate worse craving.</description>
        <time_frame>Once per week in weeks 2 through 13</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Varenicline</title>
            <description>Oral 1.0 mg BID.&#xD;
Varenicline</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Oral 1.0 mg BID.&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Average Weekly Cocaine Craving Scores Varenicline Group Versus the Placebo Group Comparator</title>
          <description>As measured by average weekly scores for cocaine craving on the brief substance craving scale combining cocaine craving frequency, intensity and duration. Minimum value 0 maximum value 12 higher scores indicate worse craving.</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="80"/>
                <count group_id="O2" value="76"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.12" spread="0.82"/>
                    <measurement group_id="O2" value="0.99" spread="0.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>17 weeks</time_frame>
      <desc>Adverse events were queried at each visit.</desc>
      <group_list>
        <group group_id="E1">
          <title>Varenicline</title>
          <description>varenicline 2 mg daily</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Identical placebo capsules</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="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>chest pain, cocaine induced</sub_title>
                <description>admitted to inpatient treatment for cocaine induced chest pain</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>mitral valve replacement</sub_title>
                <description>admitted to inpatient treatment for mitral valve replacement</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>chest pain</sub_title>
                <description>admitted to inpatient treatment for chest pain</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Lower abdominal mass</sub_title>
                <description>Hospitalization due to lower abdominal mass</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>gastroenteritis</sub_title>
                <description>Admitted to inpatient treatment for gastroenteritis</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <description>admitted to inpatient treatment for nausea</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>gunshot wound</sub_title>
                <description>admitted to inpatient treatment for a gunshot wound</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Cocaine use disorder exacerbation</sub_title>
                <description>Admitted to inpatient treatment for worsening of cocaine use disorder</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>Substance induced depression</sub_title>
                <description>Admiitted to inpatient treatment of substance induced depression</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>oiate detoxification</sub_title>
                <description>admitted to inpatient treatment for opiate detoxification</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>orthostatic hypotension</sub_title>
                <description>admitted to inpatient treatment for orthostatic hypotension</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="76"/>
              </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="80" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="67" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>elevated blood pressure</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>flatulence</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>toothache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="76"/>
              </event>
              <event>
                <sub_title>lightheadedness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>aches and pains</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>vivid dreams</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="76"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="76"/>
              </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>Kyle Kampman</name_or_title>
      <organization>Perelman School of Medicine</organization>
      <phone>215 746 2764</phone>
      <email>kampman@pennmedicine.upenn.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/NCT01680887
org study id: 814643
nct id: NCT01680887
lead sponsor: 
has dmc: Yes
This is a double-blind placebo-controlled clinical trial (n = 156) of varenicline for the
      treatment of cocaine dependence that utilizes contingency management to promote treatment
      attendance.
Background: Varenicline is a medication approved for the treatment of Tobacco Use Disorder.
      It is a partial agonist at α2β4 nicotinic acetyl choline receptors and a full agonist at α7
      nicotinic acetyl choline receptors. By its effects on cholinergic activity at α7 and α2β4
      receptors, varenicline may reduce dopaminergic and glutamatergic activity in the midbrain,
      and reduce symptoms of Cocaine Use Disorder. A preliminary trial of varenicline in human
      cocaine users suggested that varenicline treatment was associated with reductions in cocaine
      use. The current trial was intended to confirm these promising preliminary results.

      Methods: This was a 12-week, double blind, placebo controlled parallel group clinical trial
      involving 156 DSM IV cocaine dependent subjects. Subjects received 2 mg of varenicline or
      identical placebo each day along with weekly individual cognitive behavioral relapse
      prevention psychotherapy. The primary outcome measure was cocaine use measured by by thrice
      weekly urine drug screens. Additional outcome measures included cocaine withdrawal symptoms
      measured by the Cocaine Selective Severity Assessment (CSSA) End of study cocaine abstinence
      was analyzed using a Chi-square test.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants Who Report no Cocaine Use and Have no Cocaine Positive Urine Drug Screens in the Chantix Group Versus the Placebo Group Comparator During the Last Three Weeks of the Trial
time frame: weeks 11,12,13 of the trial
description: Number of subjects with cocaine abstinence as measured through three-times-weekly urine benzoylecgonine (BE) levels in urine drug screen (UDS) and self-reports of use from the Time Line Follow Back. UDS results and TLFB reports combined to yield weekly use/no-use indicators for each week of treatment.
measure: Average Weekly Cocaine Craving Scores Varenicline Group Versus the Placebo Group Comparator
time frame: Once per week in weeks 2 through 13
description: As measured by average weekly scores for cocaine craving on the brief substance craving scale combining cocaine craving frequency, intensity and duration. Minimum value 0 maximum value 12 higher scores indicate worse craving.
arm group label: Varenicline
arm group type: Experimental
description: Oral 1.0 mg BID.
arm group label: Placebo
arm group type: Placebo Comparator
description: Oral 1.0 mg BID.
intervention type: Drug
intervention name: Varenicline
arm group label: Varenicline
other name: Chantix
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Kyle M Kampman, MD
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
url: http://www.med.upenn.edu/csa/
description: University of Pennsylvania Center for Studies of Addictions
responsible party type: Sponsor
mesh term: Cocaine-Related Disorders
mesh term: Varenicline
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 