<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/NCT02218840</url>
  </required_header>
  <id_info>
    <org_study_id>14-021CTP</org_study_id>
    <nct_id>NCT02218840</nct_id>
  </id_info>
  <brief_title>Behavioral Pharmacology Associated With Cigar Smoking</brief_title>
  <official_title>Behavioral Pharmacology Associated With Cigar Smoking</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Food and Drug Administration (FDA)</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Food and Drug Administration (FDA)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Lovelace Scientific Resources is conducting clinical research study for cigar smokers. This&#xD;
      study will be evaluating the behaviors of cigar smokers and the short term effects of cigar&#xD;
      smoking.&#xD;
&#xD;
      A cigar is defined as a cylinder of tobacco wrapped in a tobacco leaf for smoking. There are&#xD;
      small cigars with filters that resemble cigarettes and large cigars that do not have filters.&#xD;
      Because cigars come in so many shapes and sizes, the nicotine content varies as well. The way&#xD;
      that a cigar smoker consumes the cigar can also have an effect on how much nicotine is&#xD;
      absorbed. This study seeks to understand nicotine consumption and addiction in cigar smokers.&#xD;
&#xD;
      Study participation will last 1 to 4 weeks and will include 2 study-related visits. Your&#xD;
      visits may include a physical exam, medical history review, questionnaires, blood&#xD;
      collections, providing a urine sample, an exhaled breath test, having your vital signs&#xD;
      collected and smoking a cigar. You will be videotaped while you smoke your cigar so that we&#xD;
      can review the technique you use while smoking.&#xD;
&#xD;
      STUDY HYPOTHESES:&#xD;
&#xD;
        -  Significant reductions in craving and withdrawal will be reported after ad libitum&#xD;
           smoking of a cigar compared to self-report prior to cigar smoking.&#xD;
&#xD;
        -  Cigar smokers will show a range of nicotine dependence, with a subset of users exceeding&#xD;
           minimal criteria for nicotine dependence.&#xD;
&#xD;
        -  Levels of nicotine, cotinine, Carbon Monoxide (CO), and&#xD;
           4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) will increase significantly from&#xD;
           pre- to post-cigar smoking.&#xD;
&#xD;
        -  Small cigar/cigarillo users will demonstrate greater levels of dependence and greater&#xD;
           relief from craving and withdrawal compared to large cigar users.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study seeks to better understand dependence behaviors in small and large cigar smokers.&#xD;
      All recruited cigar smokers will be self-defined as users on ≥ 1 day(s) per week for the past&#xD;
      6 months. They will not be currently using any other type of tobacco product for the past 6&#xD;
      months. Study subjects will smoke their own type and brand of cigar upon at least 24 hours of&#xD;
      abstinence from all tobacco products.&#xD;
&#xD;
      Dependence (both real and perceived), withdrawal relief, and craving will be measured with&#xD;
      existing and modified behavioral scales and assessments. In addition, smoking topography&#xD;
      (including latency to first puff, puff number, interpuff interval, and smoking duration),&#xD;
      self-reported inhalation behaviors, and exhaled CO will also be measured.&#xD;
&#xD;
      This is a single center, un-blinded study seeking to better understand dependence behaviors&#xD;
      in small and large cigar smokers.&#xD;
&#xD;
      Subjects will be videotaped while smoking their cigar using a digital camcorder, and the&#xD;
      video will immediately be burned to DVD for subsequent smoking topography scoring by two&#xD;
      separate raters. These raters will directly observe the subject during the cigar smoking&#xD;
      exposure.&#xD;
&#xD;
      Urine samples and serial blood samples will be collected to measure biomarkers of exposure&#xD;
      (including nicotine, cotinine, and total NNAL) before, during, and after subjects' smoking of&#xD;
      their usual type and brand of cigar. A urine creatinine lab test will be collected pre and&#xD;
      post exposure to correct for excreted cotinine levels. Subjects will be instructed to empty&#xD;
      their bladders pre cigar exposure. They will then be instructed to rehydrate based on their&#xD;
      BMI prior to the initiation of cigar smoke exposure and after 60 minutes post cigar&#xD;
      initiation. Hepatic and renal function will be assessed at screening to determine any&#xD;
      metabolism problems. Subjects will be asked to bring two (2) cigars of their usual type and&#xD;
      brand. One cigar will be used to smoke; the 2nd cigar will be used to measure total nicotine&#xD;
      content.&#xD;
&#xD;
      The cigars will be stored at ambient temperature (59º - 86º F), away from light and moisture,&#xD;
      until analysis. Nicotine concentrations will be determined from the 2nd cigar using an&#xD;
      analytical approach developed by Lovelace Biomedical Environmental Research Institute&#xD;
      (LBERI). Briefly, the cigar weight will be recorded, cigar broken apart, and mixed using a&#xD;
      mortar and pestle to create a homogenous mixture of the entire cigar. 100 mg of the cigar&#xD;
      mixture will be weighted and nicotine extracted from the tobacco using 1mL of 50/50&#xD;
      dichloromethane:dichloroethane repeated twice. The extract will be evaporated and&#xD;
      re-dissolved in 1 mL of methanol for liquid chromatography tandem mass spectrometry&#xD;
      (LC-MS/MS) analysis.&#xD;
&#xD;
      Plasma concentrations for nicotine and cotinine will be determined using LC-MS/MS and values&#xD;
      exported to Phoenix WinNonlin for pharmacokinetic analysis. Plasma Tmax and Cmax will be&#xD;
      reported using a table in a word document and in figures generated using WinNonlin. The&#xD;
      amount of cotinine and total NNAL excreted will be reported by determining the urinary&#xD;
      concentration of each compound by LC-MS/MS analysis and multiplying the determined&#xD;
      concentration by the total volume of urine recovered. Individual data along with grouped&#xD;
      results will be reported. The pharmacokinetic data will be provided to the sponsor after&#xD;
      uploading to SAS.&#xD;
&#xD;
      The subjects will be cigar smokers who are not seeking treatment for smoking cessation and&#xD;
      who are not currently using any other type of tobacco, but may be former users. They must&#xD;
      agree to abstain from smoking for at least 24 hours prior to the exposure day and will be&#xD;
      informed that they must remain abstinent from all forms of tobacco including nicotine&#xD;
      patches, gum, etc. Abstinence will be verified at the beginning of the test day through&#xD;
      expired CO and self-report. While it could be desirable to use urinary cotinine levels as a&#xD;
      further marker of abstinence, urinary cotinine levels do not appear to reach undetectable&#xD;
      levels in smokers after 24 hours. Instead, in regular smokers, negligent levels are reached&#xD;
      only after abstinence of 7-8 days, which would place significant burden on subjects for this&#xD;
      study. All subjects should be healthy males and females, 18 years of age or older, with no&#xD;
      self-reported psychiatric illnesses that would interfere with the subjects ability to&#xD;
      complete the session (i.e. schizophrenia, severe depression).&#xD;
&#xD;
      Women who are pregnant (as verified by a urine pregnancy test at Visit 1 and 2) or&#xD;
      breastfeeding will be excluded.&#xD;
&#xD;
      Subjects will be asked questions concerning the type and quantity of prescribed and&#xD;
      non-prescribed drugs that they are currently using. If, as a result of the screening, the&#xD;
      subject is determined to be ineligible to continue participation in the study, he/she will be&#xD;
      excused from further participation. A target of sixty four (64) completed subjects will be&#xD;
      recruited to ensure sufficient statistical power to test main effects across the following&#xD;
      groups:&#xD;
&#xD;
        1. Primary vs. secondary cigar users&#xD;
&#xD;
        2. Self-reported inhaling behavior vs. self-reported non-inhaling behavior&#xD;
&#xD;
        3. Small cigar (including cigarillos) vs. large cigar (including premium) users&#xD;
&#xD;
        4. White vs. non-white adults&#xD;
&#xD;
        5. Male vs. Female adults A power analysis was conducted to determine the overall sample&#xD;
           size needed to test the main effects above. According to this power analysis (see&#xD;
           below), the study will require 64 subjects assuming a balanced design across each of the&#xD;
           above factors (i.e. subjects are stratified across the 5 factors for a total of 32&#xD;
           groups). However, given the potential difficulty in filling each group of the above&#xD;
           design, we may recruit up to 50% more subjects (i.e. 96), which will ensure that each of&#xD;
           the above groups are sufficiently represented in the final sample. Finally, assuming a&#xD;
           10% dropout rate, an additional 10 subjects may be enrolled for a total sample size of&#xD;
           106.&#xD;
&#xD;
      Subjects will be monitored for adverse events (AEs) throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2014</start_date>
  <completion_date type="Actual">March 2, 2016</completion_date>
  <primary_completion_date type="Actual">January 8, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Assess Beharioral/Self-Reported Aspects of Cigar Smoking</measure>
    <time_frame>4 weeks</time_frame>
    <description>Characterize and quantify dependence, withdrawal relief, cravings, puff topography</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate smoking exposure</measure>
    <time_frame>4 weeks</time_frame>
    <description>Identifying smoking puff topography and laboratory markers of exposure (nicotine, NNAL, breath CO, and cotinine).</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">77</enrollment>
  <condition>Cigar Smoking</condition>
  <arm_group>
    <arm_group_label>Behavioral</arm_group_label>
    <description>Evaluation of cigar smoking topography</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Smoking topography</intervention_name>
    <description>Evaluation of cigar smoking topography</description>
    <arm_group_label>Behavioral</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood, urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The subjects will be cigar smokers who are not seeking treatment for smoking cessation and&#xD;
        who are not currently using any other type of tobacco, but may be former users.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing to voluntarily sign the IRB approved informed consent form (ICF)&#xD;
&#xD;
          -  Willing to complete all the requirements of the study&#xD;
&#xD;
          -  Male or Female, ≥ 18 years of age&#xD;
&#xD;
          -  Female subjects must be either:&#xD;
&#xD;
        Surgically sterile defined as having had a hysterectomy, bilateral oophorectomy, or tubal&#xD;
        ligation, amenorrheic for at least two years prior to screening visit, or otherwise&#xD;
        incapable of becoming pregnant Or Willing to practice an effective method of birth control&#xD;
        if sexually active, taking hormonal prescription oral contraceptives, progesterone implants&#xD;
        or injections, contraceptive patch, intrauterine device, or male partner with a vasectomy.&#xD;
        A double barrier method such as condoms, diaphragms, or cervical caps with spermicidal&#xD;
        foam, cream, or gel, or abstinence may be used as a method of birth control&#xD;
&#xD;
          -  Must be either a primary cigar or a secondary cigar smoker. Must have a self-reported&#xD;
             history of using cigars on ≥1 day per week for the past 6 months&#xD;
&#xD;
          -  Primary cigar users must report no significant prior use of cigarettes (&lt; 100&#xD;
             cigarettes in lifetime and no use of cigarettes in the past 6 months)&#xD;
&#xD;
          -  Secondary cigar users must self-report regular use of cigarettes in the past before&#xD;
             making the switch to cigars, and must report no use of cigarettes in the past 6 months&#xD;
&#xD;
          -  Must be able to self-report inhaling behavior as either inhaler or non-inhaler&#xD;
&#xD;
          -  Must be able to identify primary type of cigars smoked as either small cigar&#xD;
             (including cigarillos), large cigars, or premium cigars&#xD;
&#xD;
          -  English-speaking volunteers who are not seeking treatment for smoking cessation at the&#xD;
             time of the study&#xD;
&#xD;
          -  Have an exhaled carbon monoxide (CO) level of &lt;10 ppm at visit 2&#xD;
&#xD;
          -  Demonstrate no clinically significant contraindications for study participation, in&#xD;
             the judgment of the Principal Investigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women of Child Bearing Potential (WOCBP) with a positive urine human chorionic&#xD;
             gonadotropin (Urine β- hCG) pregnancy test within 10 days prior to Visit 2&#xD;
&#xD;
          -  Pregnant and/or nursing females&#xD;
&#xD;
          -  Use of any other type tobacco product (except cigars), non-tobacco nicotine-containing&#xD;
             product(s), smoking cessation medications, such as varenicline (Chantix®) and&#xD;
             bupropion (Zyban®), or NRT (Nicotine Replacement Therapy) within 60 days of study&#xD;
             enrollment&#xD;
&#xD;
          -  Have any previous self-reported medical adverse reaction to nicotine or tobacco, (for&#xD;
             example nausea, headache and chest pain)&#xD;
&#xD;
          -  Subjects who self-report a clinically significant concomitant disease or illness at&#xD;
             either screening or visit 2, including but not limited to depression, schizophrenia,&#xD;
             uncontrolled respiratory or cardiovascular disease, which in the opinion of the&#xD;
             Principal Investigator or designee would preclude safe and /or successful completion&#xD;
             of this study&#xD;
&#xD;
          -  Subject demonstrates an elevated liver function of ≥ 2 times the upper limit of normal&#xD;
             at screening&#xD;
&#xD;
          -  Subject demonstrates an elevated renal function of ≥ 2 times the upper limit of normal&#xD;
             at screening&#xD;
&#xD;
          -  Subject intends to stop smoking cigars in the next month&#xD;
&#xD;
          -  Unwilling to abstain from cigar smoking and all tobacco and nicotine use for at least&#xD;
             24 hours prior to exposure, Visit 2&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael R McGuire, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lovelace Scientific Resources, Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lovelace Scientific Resources, Inc</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <last_update_submitted>February 24, 2023</last_update_submitted>
  <last_update_submitted_qc>February 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cigar smoker</keyword>
  <keyword>smoking</keyword>
  <keyword>behavioral pharmacology</keyword>
  <keyword>smoking topography</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02218840
org study id: 14-021CTP
nct id: NCT02218840
lead sponsor: 
has dmc: Yes
Lovelace Scientific Resources is conducting clinical research study for cigar smokers. This
      study will be evaluating the behaviors of cigar smokers and the short term effects of cigar
      smoking.

      A cigar is defined as a cylinder of tobacco wrapped in a tobacco leaf for smoking. There are
      small cigars with filters that resemble cigarettes and large cigars that do not have filters.
      Because cigars come in so many shapes and sizes, the nicotine content varies as well. The way
      that a cigar smoker consumes the cigar can also have an effect on how much nicotine is
      absorbed. This study seeks to understand nicotine consumption and addiction in cigar smokers.

      Study participation will last 1 to 4 weeks and will include 2 study-related visits. Your
      visits may include a physical exam, medical history review, questionnaires, blood
      collections, providing a urine sample, an exhaled breath test, having your vital signs
      collected and smoking a cigar. You will be videotaped while you smoke your cigar so that we
      can review the technique you use while smoking.

      STUDY HYPOTHESES:

        -  Significant reductions in craving and withdrawal will be reported after ad libitum
           smoking of a cigar compared to self-report prior to cigar smoking.

        -  Cigar smokers will show a range of nicotine dependence, with a subset of users exceeding
           minimal criteria for nicotine dependence.

        -  Levels of nicotine, cotinine, Carbon Monoxide (CO), and
           4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) will increase significantly from
           pre- to post-cigar smoking.

        -  Small cigar/cigarillo users will demonstrate greater levels of dependence and greater
           relief from craving and withdrawal compared to large cigar users.
This study seeks to better understand dependence behaviors in small and large cigar smokers.
      All recruited cigar smokers will be self-defined as users on ≥ 1 day(s) per week for the past
      6 months. They will not be currently using any other type of tobacco product for the past 6
      months. Study subjects will smoke their own type and brand of cigar upon at least 24 hours of
      abstinence from all tobacco products.

      Dependence (both real and perceived), withdrawal relief, and craving will be measured with
      existing and modified behavioral scales and assessments. In addition, smoking topography
      (including latency to first puff, puff number, interpuff interval, and smoking duration),
      self-reported inhalation behaviors, and exhaled CO will also be measured.

      This is a single center, un-blinded study seeking to better understand dependence behaviors
      in small and large cigar smokers.

      Subjects will be videotaped while smoking their cigar using a digital camcorder, and the
      video will immediately be burned to DVD for subsequent smoking topography scoring by two
      separate raters. These raters will directly observe the subject during the cigar smoking
      exposure.

      Urine samples and serial blood samples will be collected to measure biomarkers of exposure
      (including nicotine, cotinine, and total NNAL) before, during, and after subjects' smoking of
      their usual type and brand of cigar. A urine creatinine lab test will be collected pre and
      post exposure to correct for excreted cotinine levels. Subjects will be instructed to empty
      their bladders pre cigar exposure. They will then be instructed to rehydrate based on their
      BMI prior to the initiation of cigar smoke exposure and after 60 minutes post cigar
      initiation. Hepatic and renal function will be assessed at screening to determine any
      metabolism problems. Subjects will be asked to bring two (2) cigars of their usual type and
      brand. One cigar will be used to smoke; the 2nd cigar will be used to measure total nicotine
      content.

      The cigars will be stored at ambient temperature (59º - 86º F), away from light and moisture,
      until analysis. Nicotine concentrations will be determined from the 2nd cigar using an
      analytical approach developed by Lovelace Biomedical Environmental Research Institute
      (LBERI). Briefly, the cigar weight will be recorded, cigar broken apart, and mixed using a
      mortar and pestle to create a homogenous mixture of the entire cigar. 100 mg of the cigar
      mixture will be weighted and nicotine extracted from the tobacco using 1mL of 50/50
      dichloromethane:dichloroethane repeated twice. The extract will be evaporated and
      re-dissolved in 1 mL of methanol for liquid chromatography tandem mass spectrometry
      (LC-MS/MS) analysis.

      Plasma concentrations for nicotine and cotinine will be determined using LC-MS/MS and values
      exported to Phoenix WinNonlin for pharmacokinetic analysis. Plasma Tmax and Cmax will be
      reported using a table in a word document and in figures generated using WinNonlin. The
      amount of cotinine and total NNAL excreted will be reported by determining the urinary
      concentration of each compound by LC-MS/MS analysis and multiplying the determined
      concentration by the total volume of urine recovered. Individual data along with grouped
      results will be reported. The pharmacokinetic data will be provided to the sponsor after
      uploading to SAS.

      The subjects will be cigar smokers who are not seeking treatment for smoking cessation and
      who are not currently using any other type of tobacco, but may be former users. They must
      agree to abstain from smoking for at least 24 hours prior to the exposure day and will be
      informed that they must remain abstinent from all forms of tobacco including nicotine
      patches, gum, etc. Abstinence will be verified at the beginning of the test day through
      expired CO and self-report. While it could be desirable to use urinary cotinine levels as a
      further marker of abstinence, urinary cotinine levels do not appear to reach undetectable
      levels in smokers after 24 hours. Instead, in regular smokers, negligent levels are reached
      only after abstinence of 7-8 days, which would place significant burden on subjects for this
      study. All subjects should be healthy males and females, 18 years of age or older, with no
      self-reported psychiatric illnesses that would interfere with the subjects ability to
      complete the session (i.e. schizophrenia, severe depression).

      Women who are pregnant (as verified by a urine pregnancy test at Visit 1 and 2) or
      breastfeeding will be excluded.

      Subjects will be asked questions concerning the type and quantity of prescribed and
      non-prescribed drugs that they are currently using. If, as a result of the screening, the
      subject is determined to be ineligible to continue participation in the study, he/she will be
      excused from further participation. A target of sixty four (64) completed subjects will be
      recruited to ensure sufficient statistical power to test main effects across the following
      groups:

        1. Primary vs. secondary cigar users

        2. Self-reported inhaling behavior vs. self-reported non-inhaling behavior

        3. Small cigar (including cigarillos) vs. large cigar (including premium) users

        4. White vs. non-white adults

        5. Male vs. Female adults A power analysis was conducted to determine the overall sample
           size needed to test the main effects above. According to this power analysis (see
           below), the study will require 64 subjects assuming a balanced design across each of the
           above factors (i.e. subjects are stratified across the 5 factors for a total of 32
           groups). However, given the potential difficulty in filling each group of the above
           design, we may recruit up to 50% more subjects (i.e. 96), which will ensure that each of
           the above groups are sufficiently represented in the final sample. Finally, assuming a
           10% dropout rate, an additional 10 subjects may be enrolled for a total sample size of
           106.

      Subjects will be monitored for adverse events (AEs) throughout the study.
observational model: Cohort
time perspective: Prospective
measure: Assess Beharioral/Self-Reported Aspects of Cigar Smoking
time frame: 4 weeks
description: Characterize and quantify dependence, withdrawal relief, cravings, puff topography
measure: Evaluate smoking exposure
time frame: 4 weeks
description: Identifying smoking puff topography and laboratory markers of exposure (nicotine, NNAL, breath CO, and cotinine).
arm group label: Behavioral
description: Evaluation of cigar smoking topography
intervention type: Other
intervention name: Smoking topography
description: Evaluation of cigar smoking topography
arm group label: Behavioral
blood, urine
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Michael R McGuire, MD
role: Principal Investigator
affiliation: Lovelace Scientific Resources, Inc
facility: 
country: United States
responsible party type: Sponsor