Clinical trial NCT04079933: A Study to Evaluate Changes in Smokers Using An Oral Tobacco-Derived Nicotine Product
Official title: A Randomized, Controlled, Parallel Group Clinical Study of Cigarette Smokers Using an Innovative Oral Tobacco-derived Nicotine Product to Determine Impact on Cigarette Consumption and Biomarkers of Exposure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tobacco Use
Lead sponsor: Altria Client Services LLC
Sponsor class: INDUSTRY
First posted: 2019-09-06
Enrollment: 154
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this study was to estimate changes in biomarkers of exposure (BOE) in adult cigarette smokers using an oral tobacco-derived nicotine (OTDN) product relative to adult smokers who continue smoking exclusively.

Detailed description: This was a randomized, controlled, open-label, parallel group, multicenter, 9-week study to determine changes in BOE in adult smokers allowed ad libitum use of an OTDN product relative to adult smokers who were not allowed to use an OTDN product. This study was conducted in adult smokers who were considered to be in overall good health. Subjects were randomized to Test (allowed OTDN use) or Control (not allowed OTDN use) groups.

Eligibility criteria: Inclusion Criteria:

Subject must:

1. sign an Institutional Review Board (IRB)-approved Informed Consent Form (ICF) for the study.
2. be between the ages of 21 and 65 years, inclusive, at the time of Screening.
3. have consumed a minimum of 10 manufactured cigarettes per day (CPD) daily during the last 6 months (entire 6 month period must have occurred after subject turned 21 years of age).
4. indicate that he/she smokes cigarettes "every day" at Screening and on Day 1
5. be able to fully comprehend the English language.
6. have an active phone number and must have daily access to a touchtone phone between 1600 and 1900 hours.
7. be interested in alternative tobacco products to cigarettes at Screening.
8. indicate that they "definitely would buy" or "probably would buy" on the VBM-FG2 Potential Purchase Interest Questionnaire.
9. be in generally good health.
10. if female, have a negative urine dipstick pregnancy test.
11. if female heterosexually active and of childbearing potential (i.e., not surgically sterile or two years naturally postmenopausal), agree to use a medically accepted method of contraception from Screening through the End of Study.
12. have clinical laboratory tests within the appropriate reference range or which are clinically acceptable to the Investigator.
13. have a negative ethanol, amphetamines, opiates, cannabinoids, and cocaine urine drug screen.
14. test negative for human immunodeficiency (HIV), hepatitis B (hepatitis B surface antigen \[HBsAg\]), and Hepatitis C (anti-hepatitis C virus antibody \[anti-HCV\]).
15. be willing and able to comply with the requirements of the study.

Exclusion Criteria:

Subject must not:

1. be pregnant, nursing, or planning to become pregnant during the study period.
2. indicate that he/she intends to quit smoking within the next 30 days (at Screening or on Day 1).
3. have uncontrolled hypertension, history of coronary heart disease or other significant heart conditions, and/or other significant medical conditions that might interfere with study procedures.
4. have used prescription anti-diabetic medication and/or insulin therapy within 12 months of Day 1.
5. have a history of drug or alcohol abuse within the 24 months prior to Screening.
6. have participated in a clinical study for an investigational drug, device, or biologic within 30 days prior to enrollment (Day 1).
7. be a current user of nicotine replacement therapy (indicate every day or some days on Subject Screener/Tobacco History Questionnaire).
8. be a current or former employee of the tobacco industry or a first-degree relative (e.g., parent, sibling, child) of a current or former employee of the tobacco industry.
9. have been involved in the development of the study design/conduct or be a first-degree relative (e.g., parent, sibling, child) of someone involved in the development of the study design/conduct.
10. be a current employee or personnel involved with the study at the study site.
11. be currently participating in the study at a different study site (i.e., each subject can only be in the study population once).

Primary outcomes:
measure: Summary Statistics of Percent Change From Baseline for Urinary Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) (%) (Per-Protocol Population)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
Secondary outcomes:
measure: Summary Statistics of Change From Baseline for Urinary Total NNAL (ng/g Creatinine) (Per-Protocol Population)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Summary Statistics of Change From Baseline for Nicotine Equivalents (mg / g Creatinine) (Per-Protocol Population)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Summary Statistics of Percent Change From Baseline for Nicotine Equivalents (%) (Per-Protocol Population)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Summary Statistics of Change From Baseline for S-phenyl Mercapturic Acid (S-PMA) (ng/g Creatinine) (Per-Protocol Population)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Summary Statistics of Percent Change From Baseline for S-PMA (%) (Per-Protocol Population)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Summary Statistics of Change From Baseline for Carboxyhemoglobin (%) (Per-Protocol Population)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Summary Statistics of Percent Change From Baseline for Carboxyhemoglobin (%) (Per-Protocol Population)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Summary Statistics of Change From Baseline for Exhaled Carbon Monoxide (Ppm) (Per-Protocol Population)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Summary Statistics of Percent Change From Baseline for Exhaled Carbon Monoxide (%) (Per-Protocol Population)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Summary Statistics of Change From Baseline in Cigarettes Smoked Per Day (Per-Protocol Population)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Summary Statistics of Percent Change From Baseline for Cigarettes Smoked Per Day (CPD) (Per-Protocol Population)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Summary Statistics of Change From Baseline for Total Score of Fagerstrom Test for Cigarette Dependence (Per-Protocol Population)
timeFrame: Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Count of Subjects in Subgroups Based on Change From Baseline to End of Study on Change in Quit Attempts (Per-Protocol)
timeFrame: Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Count of Subjects in Subgroups Based on Change From Baseline to End of Study on Change in Quitting Intentions (Per-Protocol)
timeFrame: Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Difference in Means of Urinary Total NNAL Exposure Between Day 1 and Day 8 (Per-Protocol)
timeFrame: Daily during Baseline Period (Day 1 to Day 8)
measure: Difference in Means of Nicotine Equivalents Exposure Between Day 1 and Day 8 (Per-Protocol)
timeFrame: Daily during Baseline Period (Day 1 to Day 8)
measure: Difference in Means of S-PMA Exposure Between Day 1 and Day 8 (Per-Protocol)
timeFrame: Daily during Baseline Period (Day 1 to Day 8)
measure: Difference in Means of Carboxyhemoglobin (COHb) Exposure Between Day 1 and Day 8 (Per-Protocol)
timeFrame: Daily during Baseline Period (Day 1 to Day 8)
measure: Difference in Means of Carbon Monoxide (CO) Exposure Between Day 1 and Day 8 (Per-Protocol)
timeFrame: Daily during Baseline Period (Day 1 to Day 8)
measure: Difference in Cigarettes Per Day Between the Once Weekly Recall at Day 8 (From Questionnaire) and the Average Daily Tracking Days 2 Through 8 (From IVRS) (Per-Protocol)
timeFrame: Daily during Baseline Period (Day 1 to Day 8)
measure: Frequency and Percentage of Subjects With Change From Baseline in Cigarette Consumption
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7)
measure: Frequency and Percentage of Subjects With Change From Baseline in Urinary Total NNAL (ng / g Creatinine)
timeFrame: Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7)
measure: Frequency and Percentage of Subjects With Change From Baseline in Quitting Intentions
timeFrame: Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
measure: Summary Statistics of Cigarettes Smoked Per Day on Visits 2 (Day 1) and 3 (Day 8)
timeFrame: Day 1 (Visit 2) and Day 8 (Visit 3)
measure: Summary Statistics of Carboxyhemoglobin by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 1 (Visit 2), Day 8 (Visit 3), Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7)
measure: Summary Statistics of Exhaled Carbon Monoxide by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 1 (Visit 2), Day 8 (Visit 3), Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7)
measure: Summary Statistics of S-PMA by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 1 (Visit 2), Day 8 (Visit 3), Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7)
measure: Descriptive Statistics for Cigarettes Smoked Per Day (CPD) (Recall Data) in Day 1 and 8 (Respectively) by Study Group and Cigarette Consumption Categories
timeFrame: Day 1 (Visit 2) and Day 8 (Visit 3)
measure: Summary Statistics of Cigarettes Smoked Per Day (IVRS Data) by Study Group and Cigarette Consumption Categories on Days 1 Through 8
timeFrame: Daily during Baseline Period (Day 1 to Day 8)
measure: Median Change From Baseline to End of Study for Urinary Total NNAL by Study Group
timeFrame: Day 8 (Visit 3) and End of Study (Day 36±1)
measure: Median Change From Baseline to End of Study for Urinary Total NNAL by Study Group and Cigarette Consumption Categories
timeFrame: Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
measure: Change From Baseline to End of Study Summary Statistics of Urinary Total NNAL (ng/g Creatinine) by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
measure: Percent Change From Baseline to End of Study Summary Statistics of Urinary Total NNAL (%) by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
measure: Change From Baseline to End of Study Summary Statistics of Nicotine Equivalents (mg/g Creatinine) by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
measure: Percent Change From Baseline to End of Study Summary Statistics of Nicotine Equivalents (%) by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
measure: Change From Baseline to End of Study Summary Statistics of S-PMA (ng/g Creatinine) by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
measure: Percent Change From Baseline to End of Study Summary Statistics of S-PMA (%) by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
measure: Change From Baseline to End of Study Summary Statistics of Carboxyhemoglobin (%) by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
measure: Percent Change From Baseline to End of Study Summary Statistics of Carboxyhemoglobin (%) by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
measure: Change From Baseline to End of Study Summary Statistics of Exhaled Carbon Monoxide (Ppm) by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
measure: Percent Change From Baseline to End of Study Summary Statistics of Exhaled Carbon Monoxide (%) by Study Group and Cigarette Consumption Categories Over Visits
timeFrame: Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
measure: Characterization of Subgroups Based on Change From Baseline in Total NNAL
timeFrame: Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Covance Daytona Clinical Research Unit
state: Florida
city: Evansville
country: United States
facility: Covance Evansville Clinical Research Unit
state: Indiana
city: Dallas
country: United States
facility: Covance Dallas Clinical Research Unit
state: Texas
Study officials:
affiliation: Altria Client Services LLC
name: Jeffery S Edmiston, PhD
role: STUDY_DIRECTOR
References: