A Study to Evaluate Changes in Smokers Using An Oral Tobacco-Derived Nicotine Product

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

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.

Study Overview

• Status: Completed
• Conditions: Tobacco Use
• Intervention / Treatment: Other: Oral tobacco-derived nicotine product (OTDN)

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.

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Daytona Clinical Research Unit
  • Indiana
    • Evansville, Indiana, United States, 47710
      • Covance Evansville Clinical Research Unit
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Dallas Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Group 1: Continue Smoking; Subjects were asked to continue smoking their own brand of cigarettes ad libitum for 4 weeks
Experimental: Group 2: OTDN; Subjects were allowed to continue smoking their own brand of cigarettes ad libitum and provided the option to use an OTDN (specifically, VERVE® Discs Blue Mint [VBM-FG2]) also under ad libitum conditions	Other: Oral tobacco-derived nicotine product (OTDN); Other Names: VERVE® Discs Blue Mint, VBM-FG2 oral discs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary Statistics of Percent Change From Baseline for Urinary Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) (%) (Per-Protocol Population)	Summary statistics of percent change from baseline for urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL] (%) in each study visit are presented. Baseline taken from Visit 3 (Day 8±1) value. Visit 4 = Day 15±1 Visit 5 = Day 22±1 Visit 6 = Day 29±1 Visit 7/End of Study = Day 36±1 Mean percent change from baseline is the mean of all individual subjects' percent change from baseline values. Each percent change from baseline was calculated by subtracting the individual subject's baseline value from the value at the desired timepoint and then dividing this calculated value by the individual subject's baseline value and multiplying by 100. These individual subjects' percent changes from baseline values were used to calculate the mean percent change from baseline using a Statistical Analysis System (SAS®) procedure.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary Statistics of Change From Baseline for Urinary Total NNAL (ng/g Creatinine) (Per-Protocol Population)	Summary statistics of change from baseline for urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL] (ng/g creatinine) in each study visit are presented. Baseline taken from Visit 3 (Day 8±1) value. Visit 4 = Day 15±1 Visit 5 = Day 22±1 Visit 6 = Day 29±1 Visit 7/End of Study = Day 36±1	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)
Summary Statistics of Change From Baseline for Nicotine Equivalents (mg / g Creatinine) (Per-Protocol Population)	Summary statistics of change from Baseline for urinary nicotine equivalents including nicotine and its 5 metabolites (cotinine, trans-3'-hydroxycotinine, trans-3'-hydroxycotinine-0-glucuronide, nicotine-N-glucuronide, and cotinine-N-glucuronide) (mg/g creatinine) in each study visit are presented. Baseline taken from Visit 3 (Day 8±1) value. Visit 4 = Day 15±1 Visit 5 = Day 22±1 Visit 6 = Day 29±1 Visit 7/End of Study = Day 36±1	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)
Summary Statistics of Percent Change From Baseline for Nicotine Equivalents (%) (Per-Protocol Population)	Summary statistics of percent change from Baseline for urinary nicotine equivalents including nicotine and its 5 metabolites (cotinine, trans-3'-hydroxycotinine, trans-3'-hydroxycotinine-0-glucuronide, nicotine-N-glucuronide, and cotinine-N-glucuronide) (%) in each study visit are presented. Baseline taken from Visit 3 (Day 8±1) value. Visit 4 = Day 15±1 Visit 5 = Day 22±1 Visit 6 = Day 29±1 Visit 7/End of Study = Day 36±1 Mean percent change from baseline is the mean of all individual subjects' percent change from baseline values. Each percent change from baseline was calculated by subtracting the individual subject's baseline value from the value at the desired timepoint and then dividing this calculated value by the individual subject's baseline value and multiplying by 100. These individual subjects' percent changes from baseline values were used to calculate the mean percent change from baseline using a SAS® procedure.	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)
Summary Statistics of Change From Baseline for S-phenyl Mercapturic Acid (S-PMA) (ng/g Creatinine) (Per-Protocol Population)	Summary statistics of change from Baseline for urinary S-phenyl mercapturic acid [S-PMA] (ng/g creatinine) in each study visit are presented. Baseline taken from Visit 3 (Day 8±1) value. Visit 4 = Day 15±1 Visit 5 = Day 22±1 Visit 6 = Day 29±1 Visit 7/End of Study = Day 36±1	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)
Summary Statistics of Percent Change From Baseline for S-PMA (%) (Per-Protocol Population)	Summary statistics of percent change from Baseline for urinary S-phenyl mercapturic acid [S-PMA] (%) in each study visit are presented. Baseline taken from Visit 3 (Day 8±1) value. Visit 4 = Day 15±1 Visit 5 = Day 22±1 Visit 6 = Day 29±1 Visit 7/End of Study = Day 36±1 Mean percent change from baseline is the mean of all individual subjects' percent change from baseline values. Each percent change from baseline was calculated by subtracting the individual subject's baseline value from the value at the desired timepoint and then dividing this calculated value by the individual subject's baseline value and multiplying by 100. These individual subjects' percent changes from baseline values were used to calculate the mean percent change from baseline using a SAS® procedure.	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)
Summary Statistics of Change From Baseline for Carboxyhemoglobin (%) (Per-Protocol Population)	Summary statistics of change from Baseline for blood carboxyhemoglobin (%) in each study visit are presented. Baseline taken from Visit 3 (Day 8±1) value. Visit 4 = Day 15±1 Visit 5 = Day 22±1 Visit 6 = Day 29±1 Visit 7/End of Study = Day 36±1	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)
Summary Statistics of Percent Change From Baseline for Carboxyhemoglobin (%) (Per-Protocol Population)	Summary statistics of percent change from Baseline for blood carboxyhemoglobin (%) in each study visit are presented. Baseline taken from Visit 3 (Day 8±1) value. Visit 4 = Day 15±1 Visit 5 = Day 22±1 Visit 6 = Day 29±1 Visit 7/End of Study = Day 36±1 Mean percent change from baseline is the mean of all individual subjects' percent change from baseline values. Each percent change from baseline was calculated by subtracting the individual subject's baseline value from the value at the desired timepoint and then dividing this calculated value by the individual subject's baseline value and multiplying by 100. These individual subjects' percent changes from baseline values were used to calculate the mean percent change from baseline using a SAS® procedure.	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)
Summary Statistics of Change From Baseline for Exhaled Carbon Monoxide (Ppm) (Per-Protocol Population)	Summary statistics of change from Baseline for exhaled carbon monoxide (ppm) in each study visit are presented. Baseline taken from Visit 3 (Day 8±1) value. Visit 4 = Day 15±1 Visit 5 = Day 22±1 Visit 6 = Day 29±1 Visit 7/End of Study = Day 36±1	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)
Summary Statistics of Percent Change From Baseline for Exhaled Carbon Monoxide (%) (Per-Protocol Population)	Summary statistics of percent change from Baseline for exhaled carbon monoxide (%) in each study visit are presented. Baseline taken from Visit 3 (Day 8±1) value. Visit 4 = Day 15±1 Visit 5 = Day 22±1 Visit 6 = Day 29±1 Visit 7/End of Study = Day 36±1 Mean percent change from baseline is the mean of all individual subjects' percent change from baseline values. Each percent change from baseline was calculated by subtracting the individual subject's baseline value from the value at the desired timepoint and then dividing this calculated value by the individual subject's baseline value and multiplying by 100. These individual subjects' percent changes from baseline values were used to calculate the mean percent change from baseline using a SAS® procedure.	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)
Summary Statistics of Change From Baseline in Cigarettes Smoked Per Day (Per-Protocol Population)	Summary statistics of change from Baseline in number or products used day in each study visit are presented. Values for visit are the average of daily values for the previous week Visit 4 = Day 15±1 Visit 5 = Day 22±1 Visit 6 = Day 29±1 Visit 7/End of Study = Day 36±1	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)
Summary Statistics of Percent Change From Baseline for Cigarettes Smoked Per Day (CPD) (Per-Protocol Population)	Summary statistics of percent change from Baseline of number of products used per day in each study visit are presented. CPD was tracked using an interactive voice response system (IVRS). During the Baseline Period (Days 1 to 8), subjects reported CPD daily through an IVRS each day between 16:00 and 19:00. Test and Control subjects continued daily tobacco use tracking via an IVRS and return to the study site once a week during the 4 week Product Use Period on Days 15, 22, 29, and 36. Mean percent change from baseline is the mean of all individual subjects' percent change from baseline values. Each percent change from baseline was calculated by subtracting the individual subject's baseline value from the value at the desired timepoint and then dividing the calculated value by the individual subject's baseline value and multiplying by 100. These individual subjects' percent changes from baseline values were used to calculate the mean percent change from baseline using a SAS procedure.	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)
Summary Statistics of Change From Baseline for Total Score of Fagerstrom Test for Cigarette Dependence (Per-Protocol Population)	Summary statistics of change from Baseline for Total Score of Fagerstrom Test for Cigarette Dependence at the end of study/early termination are presented. The Fagerstrom Test for Nicotine Dependence consists of Yes/No and multiple-choice questions where each response is assigned a value from 0 to 1 (for yes/no questions) or 0 to 3 (for multiple-choice questions). Values are summed to yield a total score with a minimum score of 0 points and a maximum score of 10 points. The higher the total Fagerström score, the more intense is the patient's physical dependence on nicotine. Baseline = Visit 3 (Day 8) value Population: Per-Protocol	Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
Count of Subjects in Subgroups Based on Change From Baseline to End of Study on Change in Quit Attempts (Per-Protocol)	Count of Test and Control subjects that reported an increase, decrease or no change in quit attempts from Baseline to End of Study are presented. Results for the number of self-reported attempts to quit smoking in the previous 30 days were collected from subject responses to the question "How many times during the past 30 days have you stopped smoking cigarettes for 24 hours or longer because you were trying to quit?". Baseline = Visit 2 values. Population: Per-Protocol.	Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
Count of Subjects in Subgroups Based on Change From Baseline to End of Study on Change in Quitting Intentions (Per-Protocol)	Count of Test and Control subjects that reported a change (No to Yes) or no change in quitting intentions from Baseline to End of Study are presented. Results were collected from subject Yes/No responses to the question "Are you planning to quit smoking in the next 30 days?". Baseline = Visit 2 responses. Population: Per-Protocol.	Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
Difference in Means of Urinary Total NNAL Exposure Between Day 1 and Day 8 (Per-Protocol)	This secondary objective was to compare differences in the biomarker of exposure between two methods for determining CPD during the Baseline Period. Difference in mean urinary total NNAL exposure between two methods for determining daily product use (Cigarettes Per Day [CPD]) during the Baseline Period: Method 1: Recall of average daily CPD for prior week using Past 7 Day Cigarettes Use Questionnaire (Day 1). Method 2: Daily CPD tracking using an interactive voice response system (IVRS; 7 day average of values recorded on Days 2 through 8). Population: Per-Protocol.	Daily during Baseline Period (Day 1 to Day 8)
Difference in Means of Nicotine Equivalents Exposure Between Day 1 and Day 8 (Per-Protocol)	This secondary objective was to compare differences in the biomarker of exposure between two methods for determining CPD during the Baseline Period. Difference in mean urinary nicotine equivalents exposure between two methods for determining daily product use (Cigarettes Per Day [CPD]) during the Baseline Period: Method 1: Recall of average daily CPD for prior week using Past 7 Day Cigarettes Use Questionnaire (Day 1). Method 2: Daily CPD tracking using an interactive voice response system (IVRS; 7 day average of values recorded on Days 2 through 8). Nicotine equivalents include nicotine and its 5 metabolites (cotinine, trans-3'-hydroxycotinine, trans-3'-hydroxycotinine-0-glucuronide, nicotine-N-glucuronide, and cotinine-N-glucuronide) Population: Per-Protocol.	Daily during Baseline Period (Day 1 to Day 8)
Difference in Means of S-PMA Exposure Between Day 1 and Day 8 (Per-Protocol)	This secondary objective was to compare differences in the biomarker of exposure between two methods for determining CPD during the Baseline Period. Difference in mean urinary S-phenylmercapturic acid [S-PMA] exposure between two methods for determining daily product use (Cigarettes Per Day [CPD]) during the Baseline Period: Method 1: Recall of average daily CPD for prior week using Past 7 Day Cigarettes Use Questionnaire (Day 1). Method 2: Daily CPD tracking using an interactive voice response system (IVRS; 7 day average of values recorded on Days 2 through 8). Population: Per-Protocol.	Daily during Baseline Period (Day 1 to Day 8)
Difference in Means of Carboxyhemoglobin (COHb) Exposure Between Day 1 and Day 8 (Per-Protocol)	This secondary objective was to compare differences in the biomarker of exposure between two methods for determining CPD during the Baseline Period. Difference in mean blood carboxyhemoglobin [COHb] exposure between two methods for determining daily product use (Cigarettes Per Day [CPD]) during the Baseline Period: Method 1: Recall of average daily CPD for prior week using Past 7 Day Cigarettes Use Questionnaire (Day 1). Method 2: Daily CPD tracking using an interactive voice response system (IVRS; 7 day average of values recorded on Days 2 through 8). Population: Per-Protocol.	Daily during Baseline Period (Day 1 to Day 8)
Difference in Means of Carbon Monoxide (CO) Exposure Between Day 1 and Day 8 (Per-Protocol)	This secondary objective was to compare differences in the biomarker of exposure between two methods for determining CPD during the Baseline Period. Difference in mean exhaled carbon monoxide [CO] between two methods for determining daily product use (Cigarettes Per Day, CPD) during the Baseline Period: Method 1: Recall of average daily CPD for prior week using Past 7 Day Cigarettes Use Questionnaire (Day 1). Method 2: Daily CPD tracking using an interactive voice response system (IVRS; 7 day average of values recorded on Days 2 through 8). Population: Per-Protocol.	Daily during Baseline Period (Day 1 to Day 8)
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)	This secondary objective was to compare differences in the biomarker of exposure between two methods for determining CPD during the Baseline Period. Difference in product use (Cigarettes Per Day [CPD]), including test product, between two methods for determining CPD during the Baseline Period: Method 1: Recall of average daily CPD for prior week using Past 7 Day Cigarettes Use Questionnaire (Day 1). Method 2: Daily CPD tracking using an interactive voice response system (IVRS; 7 day average of values recorded on Days 2 through 8). Population: Per-Protocol.	Daily during Baseline Period (Day 1 to Day 8)
Frequency and Percentage of Subjects With Change From Baseline in Cigarette Consumption	Change in cigarette consumption, categorized as 'No change', '<50% reduction', '50% to < 100% reduction', '100% reduction' or 'Increase', among subjects in Test and Control groups are presented. Baseline values are based on the average of daily values for the week prior to randomization (Visit 3/Day 8±1).	Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7)
Frequency and Percentage of Subjects With Change From Baseline in Urinary Total NNAL (ng / g Creatinine)	Change in Urinary Total NNAL, categorized as 'No change', 'Reduction', 'Increase' or 'Missing', among subjects in Test and Control groups are presented. Baseline values are Visit 3 (Day 8) values.	Day 15 (Visit 4), Day 22 (Visit 5), Day 29 (Visit 6) and Day 36 (Visit 7)
Frequency and Percentage of Subjects With Change From Baseline in Quitting Intentions	Change in subject quitting intentions from Baseline to End of Study are presented. Subject responses were categorized as 'No to Yes', 'Yes to No' and 'Same' (no change in quitting intention). Baseline = Visit 2 (Day 1)	Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)
Summary Statistics of Cigarettes Smoked Per Day on Visits 2 (Day 1) and 3 (Day 8)	Summary statistics of average cigarettes smoked per day [CPD] over previous 7 days collected from Cigarette Use questionnaire on Visit 2 (Day 1) and Visit 3 (Day 8) are presented.	Day 1 (Visit 2) and Day 8 (Visit 3)
Summary Statistics of Carboxyhemoglobin by Study Group and Cigarette Consumption Categories Over Visits	Summary statistics of blood carboxyhemoglobin in each visit among subjects in Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented.	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)
Summary Statistics of Exhaled Carbon Monoxide by Study Group and Cigarette Consumption Categories Over Visits	Summary Statistics of exhaled carbon monoxide in each visit among subjects in Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented.	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)
Summary Statistics of S-PMA by Study Group and Cigarette Consumption Categories Over Visits	Summary statistics of urinary S-PMA (ng/g creatinine) in each visit among subjects in Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented.	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)
Descriptive Statistics for Cigarettes Smoked Per Day (CPD) (Recall Data) in Day 1 and 8 (Respectively) by Study Group and Cigarette Consumption Categories	Descriptive statistics for Cigarettes Smoked per Day (CPD) in Day 1 (Visit 2) and Day 8 (Visit 3) in Test and Control groups using recall data are presented. Subjects were sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing').	Day 1 (Visit 2) and Day 8 (Visit 3)
Summary Statistics of Cigarettes Smoked Per Day (IVRS Data) by Study Group and Cigarette Consumption Categories on Days 1 Through 8	Summary Statistics of Cigarettes Smoked per Day collected by IVRS Data method on Days 1 to 8 for Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented.	Daily during Baseline Period (Day 1 to Day 8)
Median Change From Baseline to End of Study for Urinary Total NNAL by Study Group	Median change from baseline to End of Study for urinary total NNAL in Test and Control groups are presented. Baseline = Day 8 (Visit 3) values.	Day 8 (Visit 3) and End of Study (Day 36±1)
Median Change From Baseline to End of Study for Urinary Total NNAL by Study Group and Cigarette Consumption Categories	Median Change from baseline to End of Study for urinary total NNAL in Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented. Baseline = Day 8 (Visit 3) values	Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
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	Change from Baseline to End of Study summary statistics of urinary total NNAL (ng/g Creatinine) by Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented. Baseline = Visit 3 (Day 8) values.	Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
Percent Change From Baseline to End of Study Summary Statistics of Urinary Total NNAL (%) by Study Group and Cigarette Consumption Categories Over Visits	Percent change from Baseline to End of study summary statistics of urinary total NNAL (%) for Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented. Baseline = Visit 3 (Day 8) values.	Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
Change From Baseline to End of Study Summary Statistics of Nicotine Equivalents (mg/g Creatinine) by Study Group and Cigarette Consumption Categories Over Visits	Change from Baseline to End of Study summary statistics of urinary nicotine equivalents (mg/g creatinine) by Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented. Nicotine equivalents include nicotine and its 5 metabolites (cotinine, trans-3'-hydroxycotinine, trans-3'-hydroxycotinine-0-glucuronide, nicotine-N-glucuronide, and cotinine-N-glucuronide). Baseline = Visit 3 (Day 8) values.	Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
Percent Change From Baseline to End of Study Summary Statistics of Nicotine Equivalents (%) by Study Group and Cigarette Consumption Categories Over Visits	Percent change from Baseline to End of study summary statistics of urinary nicotine equivalents (%) for Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented. Nicotine equivalents include nicotine and its 5 metabolites (cotinine, trans-3'-hydroxycotinine, trans-3'-hydroxycotinine-0-glucuronide, nicotine-N-glucuronide, and cotinine-N-glucuronide). Baseline = Visit 3 (Day 8) values.	Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
Change From Baseline to End of Study Summary Statistics of S-PMA (ng/g Creatinine) by Study Group and Cigarette Consumption Categories Over Visits	Change from Baseline to End of Study summary statistics of urinary S-phenyl mercapturic acid [S-PMA] (ng/g creatinine) by Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented. Baseline = Visit 3 (Day 8) values.	Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
Percent Change From Baseline to End of Study Summary Statistics of S-PMA (%) by Study Group and Cigarette Consumption Categories Over Visits	Percent change from Baseline to End of study summary statistics of urinary S-phenyl mercapturic acid [S-PMA] (%) for Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented. Baseline = Visit 3 (Day 8) values.	Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
Change From Baseline to End of Study Summary Statistics of Carboxyhemoglobin (%) by Study Group and Cigarette Consumption Categories Over Visits	Change from Baseline to End of Study summary statistics of blood carboxyhemoglobin (%) by Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented. Baseline = Visit 3 (Day 8) values.	Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
Percent Change From Baseline to End of Study Summary Statistics of Carboxyhemoglobin (%) by Study Group and Cigarette Consumption Categories Over Visits	Percent change from Baseline to End of study summary statistics of blood carboxyhemoglobin (%) for Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented. Baseline = Visit 3 (Day 8) values.	Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
Change From Baseline to End of Study Summary Statistics of Exhaled Carbon Monoxide (Ppm) by Study Group and Cigarette Consumption Categories Over Visits	Change from Baseline to End of Study summary statistics of exhaled carbon monoxide (ppm) by Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented. Baseline = Visit 3 (Day 8) values.	Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
Percent Change From Baseline to End of Study Summary Statistics of Exhaled Carbon Monoxide (%) by Study Group and Cigarette Consumption Categories Over Visits	Percent change from Baseline to End of study summary statistics of exhaled carbon monoxide for Test and Control groups sub-categorized by cigarette consumption categories obtained from End of Study ('Increase', 'No Change', >50% Reduction', '50 to <100% Reduction', '100% Reduction' and 'Missing') are presented. Baseline = Visit 3 (Day 8) values.	Day 8 (Visit 3) and Day 36 (Visit 7/End of Study)
Characterization of Subgroups Based on Change From Baseline in Total NNAL	Statistical analyses on the number of subjects in subgroups based on urinary total NNAL change from baseline to the last visit are presented. Baseline = Visit 3 values.	Day 36 (Visit 7/End of Study) relative to the start of the baseline period (Visit 2/Day 1)

Collaborators and Investigators

• Sponsor: Altria Client Services LLC
• Investigators: Study Director: Jeffery S Edmiston, PhD, Altria Client Services LLC

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2013
• Primary Completion (Actual): November 26, 2013
• Study Completion (Actual): November 26, 2013

Study Registration Dates

• First Submitted: August 14, 2019
• First Submitted That Met QC Criteria: September 4, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): September 27, 2024
• Last Update Submitted That Met QC Criteria: May 30, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: COV-VER-01-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No