<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/NCT03272295</url>
  </required_header>
  <id_info>
    <org_study_id>BAT1117009</org_study_id>
    <secondary_id>CA21208</secondary_id>
    <nct_id>NCT03272295</nct_id>
  </id_info>
  <brief_title>A Nicotine Pharmacokinetics and Smoking Behaviour Study Examining Cigarette Ingredients</brief_title>
  <official_title>A Randomised, Controlled, Double-Blind Study to Examine Nicotine Pharmacokinetics and Smoking Behaviour in Healthy Smokers When Smoking Cigarettes Containing Different Commonly Used Ingredients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>British American Tobacco (Investments) Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Philip Morris Products S.A.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Imperial Brands PLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Japan Tobacco Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Korea Ginseng Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>British American Tobacco (Investments) Limited</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will compare nicotine delivery and smoking behaviour in healthy subjects using&#xD;
      several combustible cigarette prototypes containing different ingredients which are commonly&#xD;
      used in the European Union.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 12, 2017</start_date>
  <completion_date type="Actual">December 8, 2017</completion_date>
  <primary_completion_date type="Actual">December 8, 2017</primary_completion_date>
  <phase>N/A</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>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>A double-blind study in respect of the site (except pharmacy) and subjects.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax</measure>
    <time_frame>-5, 1, 2, 3, 4, 5, 6, 7, 8, 15, 60, 120, 180 and 240 minutes in relation to the first puff</time_frame>
    <description>To assess the maximum nicotine concentration when subjects smoke a single cigarette</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-last</measure>
    <time_frame>-5, 1, 2, 3, 4, 5, 6, 7, 8, 15, 60, 120, 180 and 240 minutes in relation to the first puff</time_frame>
    <description>To assess the area under the concentration curve from time 0 to last the time-point when subjects smoke a single cigarette</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>-5, 1, 2, 3, 4, 5, 6, 7, 8, 15, 60, 120, 180 and 240 minutes in relation to the first puff</time_frame>
    <description>To assess the time to maximum nicotine concentration when subjects smoke a single cigarette</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Puff Volume</measure>
    <time_frame>During the time required to smoke a single cigarette (up to 8 minutes)</time_frame>
    <description>To assess puff volume when subjects smoke a single cigarette</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Puff duration</measure>
    <time_frame>During the time required to smoke a single cigarette (up to 8 minutes)</time_frame>
    <description>To assess puff duration when subjects smoke a single cigarette</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of puffs</measure>
    <time_frame>During the time required to smoke a single cigarette (up to 8 minutes)</time_frame>
    <description>To assess number of puffs when subjects smoke a single cigarette</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inhalation volume</measure>
    <time_frame>During the time required to smoke a single cigarette (up to 8 minutes)</time_frame>
    <description>To assess inhalation volume when subjects smoke a single cigarette</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exhalation volume</measure>
    <time_frame>During the time required to smoke a single cigarette (up to 8 minutes)</time_frame>
    <description>To assess exhalation volume when subjects smoke a single cigarette</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Healthy Volunteers</condition>
  <condition>Smoking</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Reference product (product 1) x 2, Single ingredients products 2, 3, 4, 5, 6 and Multiple ingredient product (product 12). Single cigarette each for nicotine PK assessment and smoking behaviour assessment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Reference product (product 1), Single ingredients products 7, 8, 9, 10, 11 and Multiple ingredient product (product 12). Single cigarette each for nicotine PK assessment and smoking behaviour assessment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Reference cigarette</intervention_name>
    <description>The reference product is based on a commercially-available king-size cigarette design (length 83 mm, circumference 24.6 mm) with a single segment cellulose acetate filter and tobacco blend recipe without ingredients.</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cigarette with carob bean extract</intervention_name>
    <description>Based on reference cigarette with added ingredient</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cigarette with cocoa powder</intervention_name>
    <description>Based on reference cigarette with added ingredient</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cigarette with fenugreek extract</intervention_name>
    <description>Based on reference cigarette with added ingredient</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cigarette with fig juice</intervention_name>
    <description>Based on reference cigarette with added ingredient</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cigarette with glycerol</intervention_name>
    <description>Based on reference cigarette with added ingredient</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cigarette with guaiacol</intervention_name>
    <description>Based on reference cigarette with added ingredient</description>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cigarette with liquorice extract powder</intervention_name>
    <description>Based on reference cigarette with added ingredient</description>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cigarette plus I-menthol</intervention_name>
    <description>Based on reference cigarette with added ingredient</description>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cigarette with propylene glycol</intervention_name>
    <description>Based on reference cigarette with added ingredient</description>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cigarette with sorbitol</intervention_name>
    <description>Based on reference cigarette with added ingredient</description>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cigarette with multiple ingredients</intervention_name>
    <description>Based on reference cigarette plus propylene glycol, glycerol, liquorice extract powder, cocoa powder, carob bean extract, fig juice concentrate, maltol, guaiacol, geraniol, fenugreek extract.</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects will be:&#xD;
&#xD;
             1.1. males or females 1.2. 21 to 55 years of age, inclusive, demonstrated by&#xD;
             appropriate proof of identification.&#xD;
&#xD;
          2. Subjects will have a:&#xD;
&#xD;
             2.1. BMI of 18.5 to 30.0 kg/m2, inclusive 2.2. body weight exceeding 52 kg (males) or&#xD;
             45 kg (females)&#xD;
&#xD;
          3. Subjects will be in good health, as judged by the PI or the appropriately qualified&#xD;
             designee based on:&#xD;
&#xD;
             3.1. medical history 3.2. physical examination 3.3. vital signs assessment 3.4.&#xD;
             12-lead ECG 3.5. clinical laboratory evaluations 3.6. lung function tests&#xD;
&#xD;
          4. Subjects will have given their written informed consent to participate in the study&#xD;
             and will have agreed to abide by the study restrictions.&#xD;
&#xD;
          5. Subjects must demonstrate the ability to comprehend the informed consent form (ICF),&#xD;
             be able to communicate well with the PI or the appropriately qualified designee,&#xD;
             understand and comply with the requirements of the study, and be judged suitable for&#xD;
             the study in the opinion of the PI or the appropriately qualified designee.&#xD;
&#xD;
          6. Subjects will be willing to refrain from consuming alcohol within 24 hours prior to&#xD;
             Admission.&#xD;
&#xD;
          7. Subjects will be regular smokers of factory made, non-menthol cigarettes whose chosen&#xD;
             brand is within the ISO tar bands 6 to 10 mg, inclusive and should not change their&#xD;
             usual brand cigarette for the duration of the study.&#xD;
&#xD;
          8. Subjects will have smoked their chosen brand for a minimum of 6 months and will have&#xD;
             smoked for at least 3 years prior to Screening, and will typically smoke at least 10&#xD;
             and a maximum of 30 CPD.&#xD;
&#xD;
          9. Subjects must have a urine cotinine level &gt;200 ng/mL and an ECO measurement of &gt;10 ppm&#xD;
             at Screening.&#xD;
&#xD;
         10. Subjects will be willing to use the study products and smoke only the study products&#xD;
             provided to them during clinical confinement and to abstain from smoking when&#xD;
             required.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Male subjects who do not agree, or whose partners of childbearing potential do not&#xD;
             agree, to use a barrier method of contraception (i.e., a condom with spermicide) in&#xD;
             addition to a second highly effective method of contraception used by their female&#xD;
             partners or to refrain from donating sperm from Admission for Visit 1 until 5-7 days&#xD;
             after Discharge.&#xD;
&#xD;
          2. Female subjects of childbearing potential who do not agree to use a highly effective&#xD;
             method of birth control in conjunction with male barrier method contraception (i.e., a&#xD;
             condom with spermicide) from the time of signing the ICF until 5-7 days after&#xD;
             Discharge.&#xD;
&#xD;
          3. Female subjects who are pregnant or breastfeeding. This will be confirmed at Screening&#xD;
             and at each Admission. Any female subject who becomes pregnant during this study will&#xD;
             be withdrawn.&#xD;
&#xD;
          4. Subjects who have donated:&#xD;
&#xD;
             4.1. ≥450 mL of blood within 90 days prior to Admission 4.2. plasma in the 7 days&#xD;
             prior to Admission 4.3. platelets in the 6 weeks prior to Admission&#xD;
&#xD;
          5. Subjects who have an acute illness (e.g., upper respiratory tract infection, viral&#xD;
             infection, etc.) requiring treatment within 4 weeks prior to Admission.&#xD;
&#xD;
          6. Subjects who have used any nicotine or tobacco product other than commercially&#xD;
             manufactured non-menthol, filter cigarettes within 14 days of Screening.&#xD;
&#xD;
          7. Subjects who are self-reported non-inhalers (smokers who draw smoke from the cigarette&#xD;
             into the mouth and throat but who do not inhale). Subjects who are determined as&#xD;
             non-inhalers at Screening will be excluded.&#xD;
&#xD;
          8. Subjects who, prior to enrolment, are planning to quit smoking in the next 12 months&#xD;
             of Screening. All subjects will be informed that they are free to quit smoking and&#xD;
             withdraw from the study at any time. Any subject who decides to quit smoking will be&#xD;
             directed to appropriate stop smoking services&#xD;
&#xD;
          9. Subjects who have a significant history of alcoholism or drug/chemical abuse within 24&#xD;
             months prior to Screening, as determined by the PI or the appropriately qualified&#xD;
             designee.&#xD;
&#xD;
         10. Subjects who have a positive urine drugs of abuse or alcohol screen (confirmed by&#xD;
             repeat) at Screening or Admission.&#xD;
&#xD;
         11. Subjects who:&#xD;
&#xD;
             11.1. have serum hepatitis 11.2. are carriers of the hepatitis B surface antigen&#xD;
             (HBsAg) 11.3. are carriers of the hepatitis C antibody 11.4. have a positive result&#xD;
             for the test for human immunodeficiency virus (HIV) antibodies.&#xD;
&#xD;
         12. Subjects who have used prescription or OTC bronchodilator medication (e.g., inhaled or&#xD;
             oral β-adrenergic agonists) to treat a chronic condition within the 12 months prior to&#xD;
             the first Admission (Visit 1) and throughout the study.&#xD;
&#xD;
         13. Subjects who have received any medications or substances (other than tobacco) which:&#xD;
&#xD;
             13.1. are known to be strong inducers or inhibitors of CYP enzymes within 14 days or 5&#xD;
             half-lives of the drug (whichever is longer) prior to the first Admission (Visit 1)&#xD;
             and throughout the study.&#xD;
&#xD;
         14. Subjects who are planning to undergo significant lifestyle changes during the study&#xD;
             e.g., big change in exercise levels.&#xD;
&#xD;
         15. Subjects who are unable to communicate effectively with the PI/study staff (i.e.,&#xD;
             language problem, poor mental development, or impaired cerebral function).&#xD;
&#xD;
         16. Subjects who are unwilling or unable to comply with the study requirements.&#xD;
&#xD;
         17. Employees, and immediate relatives, of the tobacco industry or the clinical site.&#xD;
&#xD;
         18. Subjects who are still participating in another clinical study (e.g., attending&#xD;
             follow-up visits) or who have participated in a clinical study involving&#xD;
             administration of an investigational drug (new chemical entity) in the past 3 months&#xD;
             prior to first Admission (Visit 1).&#xD;
&#xD;
         19. Subjects who have any clinically relevant abnormal findings on the physical&#xD;
             examination, medical history, ECG, lung function tests (forced expiratory volume in 1&#xD;
             second/ forced vital capacity [FEV1/FVC]), or clinical laboratory panel, unless deemed&#xD;
             not clinically significant by the PI or the appropriately qualified designee.&#xD;
&#xD;
         20. Subjects who have, or who have had a history of, any clinically significant&#xD;
             neurological, gastrointestinal, renal (including urinary tract infection or&#xD;
             nephrolithiasis), hepatic, cardiovascular, psychiatric, respiratory, metabolic,&#xD;
             endocrine, haematological or other major disorder that, in the opinion of the PI or&#xD;
             the appropriately qualified designee, would jeopardise the safety of the subject or&#xD;
             impact on the validity of the study results.&#xD;
&#xD;
         21. Subjects who have previously been diagnosed with any form of malignancy.&#xD;
&#xD;
         22. Subjects who have any clinically significant abnormal laboratory safety findings at&#xD;
             Screening and prior to first product use, as determined by the PI or the appropriately&#xD;
             qualified designee (1 repeat assessment is acceptable).&#xD;
&#xD;
         23. Subjects who have previously been randomised into or withdrawn from this study.&#xD;
&#xD;
         24. Subjects who, in the opinion of the PI or the appropriately qualified designee, should&#xD;
             not participate in this study.&#xD;
&#xD;
        Compliance with all inclusion and exclusion criteria will be reaffirmed at each study&#xD;
        Visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Johnston Stewart, MB</last_name>
    <role>Principal Investigator</role>
    <affiliation>Celerion GB Ltd</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Celerion</name>
      <address>
        <city>Belfast</city>
        <state>Northern Ireland</state>
        <zip>BT9 6AD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>August 15, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>December 6, 2022</last_update_submitted>
  <last_update_submitted_qc>December 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fenugreek seed meal</mesh_term>
    <mesh_term>Menthol</mesh_term>
    <mesh_term>Sorbitol</mesh_term>
    <mesh_term>Glycerol</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03272295
org study id: BAT1117009
secondary id: CA21208
nct id: NCT03272295
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will compare nicotine delivery and smoking behaviour in healthy subjects using
      several combustible cigarette prototypes containing different ingredients which are commonly
      used in the European Union.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
masking description: A double-blind study in respect of the site (except pharmacy) and subjects.
measure: Cmax
time frame: -5, 1, 2, 3, 4, 5, 6, 7, 8, 15, 60, 120, 180 and 240 minutes in relation to the first puff
description: To assess the maximum nicotine concentration when subjects smoke a single cigarette
measure: AUC0-last
time frame: -5, 1, 2, 3, 4, 5, 6, 7, 8, 15, 60, 120, 180 and 240 minutes in relation to the first puff
description: To assess the area under the concentration curve from time 0 to last the time-point when subjects smoke a single cigarette
measure: Tmax
time frame: -5, 1, 2, 3, 4, 5, 6, 7, 8, 15, 60, 120, 180 and 240 minutes in relation to the first puff
description: To assess the time to maximum nicotine concentration when subjects smoke a single cigarette
measure: Puff Volume
time frame: During the time required to smoke a single cigarette (up to 8 minutes)
description: To assess puff volume when subjects smoke a single cigarette
measure: Puff duration
time frame: During the time required to smoke a single cigarette (up to 8 minutes)
description: To assess puff duration when subjects smoke a single cigarette
measure: Number of puffs
time frame: During the time required to smoke a single cigarette (up to 8 minutes)
description: To assess number of puffs when subjects smoke a single cigarette
measure: Inhalation volume
time frame: During the time required to smoke a single cigarette (up to 8 minutes)
description: To assess inhalation volume when subjects smoke a single cigarette
measure: Exhalation volume
time frame: During the time required to smoke a single cigarette (up to 8 minutes)
description: To assess exhalation volume when subjects smoke a single cigarette
arm group label: Arm A
arm group type: Experimental
description: Reference product (product 1) x 2, Single ingredients products 2, 3, 4, 5, 6 and Multiple ingredient product (product 12). Single cigarette each for nicotine PK assessment and smoking behaviour assessment.
arm group label: Arm B
arm group type: Experimental
description: Reference product (product 1), Single ingredients products 7, 8, 9, 10, 11 and Multiple ingredient product (product 12). Single cigarette each for nicotine PK assessment and smoking behaviour assessment.
intervention type: Other
intervention name: Reference cigarette
description: The reference product is based on a commercially-available king-size cigarette design (length 83 mm, circumference 24.6 mm) with a single segment cellulose acetate filter and tobacco blend recipe without ingredients.
arm group label: Arm A
arm group label: Arm B
intervention type: Other
intervention name: Cigarette with carob bean extract
description: Based on reference cigarette with added ingredient
arm group label: Arm A
intervention type: Other
intervention name: Cigarette with cocoa powder
description: Based on reference cigarette with added ingredient
arm group label: Arm A
intervention type: Other
intervention name: Cigarette with fenugreek extract
description: Based on reference cigarette with added ingredient
arm group label: Arm A
intervention type: Other
intervention name: Cigarette with fig juice
description: Based on reference cigarette with added ingredient
arm group label: Arm A
intervention type: Other
intervention name: Cigarette with glycerol
description: Based on reference cigarette with added ingredient
arm group label: Arm A
intervention type: Other
intervention name: Cigarette with guaiacol
description: Based on reference cigarette with added ingredient
arm group label: Arm B
intervention type: Other
intervention name: Cigarette with liquorice extract powder
description: Based on reference cigarette with added ingredient
arm group label: Arm B
intervention type: Other
intervention name: Cigarette plus I-menthol
description: Based on reference cigarette with added ingredient
arm group label: Arm B
intervention type: Other
intervention name: Cigarette with propylene glycol
description: Based on reference cigarette with added ingredient
arm group label: Arm B
intervention type: Other
intervention name: Cigarette with sorbitol
description: Based on reference cigarette with added ingredient
arm group label: Arm B
intervention type: Other
intervention name: Cigarette with multiple ingredients
description: Based on reference cigarette plus propylene glycol, glycerol, liquorice extract powder, cocoa powder, carob bean extract, fig juice concentrate, maltol, guaiacol, geraniol, fenugreek extract.
arm group label: Arm A
arm group label: Arm B
criteria: 
gender: All
minimum age: 21 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Johnston Stewart, MB
role: Principal Investigator
affiliation: Celerion GB Ltd
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Fenugreek seed meal
mesh term: Menthol
mesh term: Sorbitol
mesh term: Glycerol