Tobacco Use
Conditions
Keywords
Very Low Nicotine, Cigarette, VLN
Brief summary
This study evaluates the impact of switching from usual brand cigarettes to very low nicotine cigarettes on cigarette consumption, smoking behavior, and biomarkers of exposure.
Detailed description
Very low nicotine (VLN) cigarettes contain a 'non-additive' level of nicotine. This study will switch smokers from their usual brand to VLN cigarettes. Periodically during the study the investigators will collect blood and measure nicotine exposure and also other biomarkers to see what effect switching has. The participants will also use a diary to record number of cigarettes smoked. Cigarette butts will also be collected.
Interventions
OTHERNon-Menthol Very Low Nicotine Cigarettes
King size non-menthol cigarettes containing 0.4mg nicotine /g tobacco
OTHERMenthol Very Low Nicotine Cigarettes
King size menthol cigarettes containing 0.4mg nicotine /g tobacco
OTHERSubject's UB non-mentholated filtered cigarettes
King size non-menthol cigarettes
OTHERSubject's UB mentholated filtered cigarettes
King size menthol cigarettes
Sponsors
Celerion
22nd Century Group, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Longitudinal ambulatory switching study
Eligibility
Sex/Gender
ALL
Age
26 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Potential subjects must fulfill all of the following inclusion criteria to be eligible for participation in the study. 1. Is a healthy adult male or female adult smoker, 26 to 65 years of age, inclusive, at Screening. 2. Has been a smoker for at least 5 years prior to Screening. Brief periods of non smoking (e.g., up to 7 consecutive days due to illness, trying to quit, participation in a study where smoking was prohibited) during that time will be permitted at the discretion of the Investigator. 3. Reports smoking an average of 10 or more manufactured combustible cigarettes per day at Screening. 4. Usual brand (UB) of cigarette is a filtered king size cigarette (with an approximate length of 84 mm (± 3 mm)). 5. Has a positive urine cotinine (≥ 500 ng/ml) at Screening. 6. Has an exhaled Carbon Monoxide \> 10 ppm at Screening. 7. If female, has a negative serum pregnancy test at Screening. 8. A female subject of childbearing potential must have been using one of the following forms of contraception and agree to continue using it through completion of the study: * hormonal (e.g., oral, vaginal ring, transdermal patch, implant, or injection) consistently for at least 3 months prior to Screening; * double barrier method (e.g., condom with spermicide, diaphragm with spermicide) consistently for at least 14 days prior to Screening; * intrauterine device for at least 3 months prior to Screening; * Essure® or similar nonsurgical sterilization procedure at least 6 months prior to Screening * a partner who has been vasectomized for at least 6 months prior to Screening; * abstinence beginning at least 14 days prior to Screening and through the End of Study. 9. A female subject of non childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to Screening: * hysteroscopic sterilization; * bilateral tubal ligation or bilateral salpingectomy; * hysterectomy; * bilateral oophorectomy; Or be postmenopausal with amenorrhea for at least 1 year prior to Day 1 and follicle stimulating hormone (FSH) levels consistent with postmenopausal status. 10. Willing to comply with the requirements of the study, including a willingness to use the test products. 11. Voluntary consent to participate in this study documented on the signed informed consent form (ICF). 12. Subject is not planning to leave the area during the course of the study.
Exclusion criteria
Subjects may be excluded from the study if there is evidence of any of the following criteria at Screening, start of Week -1 (first clinic visit), or during the study as noted, in the opinion of the Investigator. 1. History or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, pulmonary (especially bronchospastic diseases and asthma), immunologic, psychiatric, or cardiovascular disease, or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results. 2. Clinically significant abnormal findings on the physical examination, medical history, ECG, or clinical laboratory results, in the opinion of the Investigator. 3. Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV). 4. An acute illness (e.g., upper respiratory infection, viral infection) requiring treatment with prescription medication(s) within 14 days prior to Screening or first clinic visit. 5. Fever (\>100.5 degrees F) at Screening or first clinic visit. 6. Body mass index (BMI) greater than 40.0 kg/m2 or less than 18.0 kg/m2 at Screening. 7. History of drug or alcohol abuse or has used medical/recreational marijuana within 12 months of Screening. 8. Diabetes mellitus that is not controlled by diet/exercise alone, in the opinion of the Investigator. 9. Seated heart rate is lower than 40 bpm or higher than 99 bpm at Screening, unless deemed not clinically significant by the PI. 10. Seated systolic blood pressure \<90 mmHg or \>150 mmHg, diastolic blood pressure \<40 mmHg or \>95 mmHg at Screening, unless deemed not clinically significant by the PI. 11. Positive urine screen for drugs of abuse or alcohol at Screening or at the first clinic visit. 12. Female subjects who are pregnant, lactating, or intend to become pregnant from Screening through the End of Study. 13. Use of medications known to interact with cytochrome p450 2A6 (including, but not limited to, amiodarone, desipramine, isoniazid, ketoconazole, miconazole, phenobarbital, rifampin, tranylcypromine, methoxsalen) within 3 months prior to Screening and throughout the study. 14. Use of inhalers to treat any medical condition within 3 months prior to Screening and throughout the study. 15. Use of nicotine-containing products other than factory manufactured cigarettes \[e.g., roll-your-own cigarettes, e-vapor products, bidis, snuff, nicotine inhaler, pipe, cigar, chewing tobacco, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum\] within 28 days prior to Screening. 16. Use of any prescription smoking cessation treatments, including, but not limited to, varenicline (Chantix®) or buproprion (Zyban®) within 3 months prior to Screening. 17. Self-reported puffer/non-inhaler (i.e., a smoker who draws smoke from the cigarette into the mouth and throat but does not inhale). 18. Planning to quit smoking during the study period or postponing a quit attempt in order to participate in the study. 19. Plasma donation within 7 days prior to Screening or at any time during the study. 20. Donation of blood or blood products (with the exception of plasma as noted above), had significant blood loss, or received whole blood or a blood product transfusion within 56 days prior to Screening. 21. Participation in a previous clinical study for an investigational drug, device, biologic, or tobacco product within 30 days prior to Screening. 22. Subject or a first-degree relative (i.e., parent, sibling, child) is a current or former employee of the tobacco industry or a named party or class representative in litigation with the tobacco industry. 23. Subject or a first-degree relative (i.e., parent, sibling, child) is a current employee of the clinic sites.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cigarettes Per Day | Assessed daily from Week -1 to Week 6; Week -1, Week 2, and Week 6 reported | Primary objective is to measure a change in cigarette consumption behavior before, during and after switching from usual brand to to VLN cigarettes. Subjects will record their cigarette consumption daily in an electronic diary. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).All 142 randomized subjects were included in the ITT population based on product use. Out of these, 71 subjects were included in the PP Population and 71 were excluded. All excluded subjects had a ratio of \[plasma cotinine/CPD VLN\]/\[plasma cotinine/CPD baseline\] \> 0.2. It was pre-specified to exclude participants with a ratio \>0.2 as they were considered non-compliant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | -1 week, and at 2 and 6 weeks. | Total 24 hour urine will be collected to evaluate changes in NNN before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | -1 week, and at 2 and 6 weeks. | Total 24 hour urine will be collected to evaluate changes in S-PMA (benzene biomarker) before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | -1 week, and at 2 and 6 weeks. | Total 24 hour urine will be collected to evaluate changes in 3-HPMA (acrolein biomarker) before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | -1 week, and at 2 and 6 weeks. | Total 24 hour urine will be collected to evaluate changes in 1-OHP before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Biomarkers of Exposure - Total Nicotine Equivalents | -1 week, and at 2 and 6 weeks. | Total 24 hour urine will be collected to evaluate changes in total nicotine equivalents before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week -1, and at 2 and 6 weeks. | Blood will be drawn to evaluate COHb before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Biomarkers of Exposure -Cotinine | Week -1, and at 2 and 6 weeks. | Blood will be drawn to evaluate cotinine levels before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per pre-switch Arms/Group assignment. |
| Nicotine Pharmacokinetics - Maximum Nicotine Concentration (C-Max) | Week -1, and at 2 and 6 weeks. | Blood samples will be drawn at -5, 2, 5, 7, 10, 12, 15, 20, 30, 45, 60, 90, 120, 150 and 180 minutes relative to the start of cigarette smoking a single cigarette for determination of C-max at weeks -1, 2 and 6. The baseline data were collected for participants at Week -1, and Week -1 data are reported per pre-switch Arms/Group assignment. |
| Nicotine Pharmacokinetics - Peak Nicotine Time (T-Max) | Week -1, and at 2 and 6 weeks. | Blood samples will be drawn at -5, 2, 5, 7, 10, 12, 15, 20, 30, 45, 60, 90, 120, 150 and 180 minutes relative to the start of cigarette smoking a single cigarette for determination of T-Max at weeks -1, 2 and 6. The baseline data were collected for participants at Week -1, and Week -1 data are reported per pre-switch Arms/Group assignment. |
| Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | -1 week, and at 2 and 6 weeks. | Total 24 hour urine will be collected to evaluate changes in NNAL (4-methylnitrosamino)-1-3-pyridyl)-1-butanone biomarker) before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Smoking Topography - Puff Duration | -1 week, and at 2 and 6 weeks. | Puff duration will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Smoking Topography - Puff Volume | -1 week, and at 2 and 6 weeks. | Puff volume will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Smoking Topography - Peak Puff Flow Rate | -1 week, and at 2 and 6 weeks. | Peak Puff Flow Rate will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Smoking Topography - Average Flow Rate | -1 week, and at 2 and 6 weeks. | Average Puff Flow Rate will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Smoking Topography - Inter-puff Interval | -1 week, and at 2 and 6 weeks. | Inter-puff interval will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | -1 week, and at 2, 4, and 6 weeks. | Subjects will answer a Fagerstrom Test for Cigarette Dependance (FTCD) questionnaire which contains six items that evaluate the quantity of cigarette consumption, the compulsion to use, and dependence.The Fagerstrom Test for Nicotine Dependence, is scored from 0 to 1 for yes/no items and 0 to 3 for multiple-choice items.The items are summed to yield a total score of 0-10. The higher the total Fagerström score, the greater the patient's physical dependence on nicotine. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week -1, and at 2, 4, and 6 weeks. | Subjects will answer a Brief Questionnaire of Smoking Urges (QSU-Brief). QSU is on a scale of 1-7, with 1 being strongly disagree and 7 being strongly agree. The average score of the following is taken to determine the Factor Score 1 and Factor Score 2; Factor 1: Average of Questions 1, 3, 6, 7, and 10; Factor 2: Average of Questions 2, 4, 5, 8, and 9. The score for each factor is calculated by summing the item scores; the total score is calculated by summing all questions together. The higher the score, the greater the urge to smoke. The total score range for this questionnaire is 10-70. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | -1 week, and at 2, 4, and 6 weeks. | Subjects will answer a MNWS-R questionnaire. The MNWS is considered as the briefest scale among the self-report measures of nicotine withdrawal symptoms currently available. The original MNWS was developed by Hughes and Hatsukami in 1986. It consisted of nine nicotine withdrawal symptoms including craving. The scale was modified to reflect changes made in the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for nicotine withdrawal. The total score of the scale range from 0 to 36 depending on participant's rate for the symptoms as not present (0), slight (1), mild (2), moderate (3), and severe (4). A high total score implies high nicotine addiction. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Subjective Effects - Perceived Health Risks | -1 week, and at 2, 4, and 6 weeks. | Subjects will answer a Perceived health risks questionnaire. The subjects indicated their perception of the risk of becoming addicted to the cigarette they were currently using on a scale from 1 to 10. Scale =1 was a very low risk of becoming addicted and Scale =10 was a very high risk of becoming addicted. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment). |
| Nicotine Pharmacokinetics - Area Under Nicotine Concentration Curve (AUC) | Week -1, and at 2 and 6 weeks. | Blood samples will be drawn at -5, 2, 5, 7, 10, 12, 15, 20, 30, 45, 60, 90, 120, 150 and 180 minutes relative to the start of cigarette smoking a single cigarette for determination of AUC at weeks -1, 2 and 6. The baseline data were collected for participants at Week -1, and Week -1 data are reported per pre-switch Arms/Group assignment. |
Countries
United States
Participant flow
Recruitment details
A total of 142 smokers were recruited from two sites in the United States; Celerion, Lincoln Nebraska and High Point Clinical Trials Center, High Point, North Carolina. The participants were recruited via social media, print, TV, radio, referrals.
Pre-assignment details
Subjects may have been excluded from the study if there was evidence of any of the exclusion criteria during the study as noted, in the opinion of the Investigator.
Participants by arm
| Arm | Count |
|---|---|
| Non-Menthol Very Low Nicotine Cigarettes Subjects will be switched from their usual brand to smoke Very Low Nicotine king size cigarettes
Non-Menthol Very Low Nicotine Cigarettes: King size non-menthol cigarettes containing 0.4mg nicotine /g tobacco | 50 |
| Menthol Very Low Nicotine Cigarettes Subjects will be switched from their usual brand to smoke Very Low Nicotine king size Menthol cigarettes
Menthol Very Low Nicotine Cigarettes: King size menthol cigarettes containing 0.4mg nicotine /g tobacco | 50 |
| Usual Brand Non-Mentholated Subjects will continue to use their usual brand non-menthol cigarettes | 22 |
| Usual Brand Mentholated Subjects will continue to use their usual brand menthol cigarettes | 20 |
| Total | 142 |
Baseline characteristics
| Characteristic | Non-Menthol Very Low Nicotine Cigarettes | Menthol Very Low Nicotine Cigarettes | Usual Brand Non-Mentholated | Usual Brand Mentholated | Total |
|---|---|---|---|---|---|
| Age, Continuous | 45.9 years STANDARD_DEVIATION 10.85 | 40.5 years STANDARD_DEVIATION 9.34 | 45.8 years STANDARD_DEVIATION 12.39 | 42.7 years STANDARD_DEVIATION 10.82 | 43.5 years STANDARD_DEVIATION 10.76 |
| Cigarettes Per Day (CPD) | 19.8 Cigarettes per day STANDARD_DEVIATION 6.92 | 15.4 Cigarettes per day STANDARD_DEVIATION 6.19 | 18.2 Cigarettes per day STANDARD_DEVIATION 3.85 | 17.1 Cigarettes per day STANDARD_DEVIATION 6.16 | 17.6 Cigarettes per day STANDARD_DEVIATION 6.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 49 Participants | 21 Participants | 19 Participants | 138 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 29 Participants | 2 Participants | 12 Participants | 46 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 44 Participants | 17 Participants | 18 Participants | 8 Participants | 87 Participants |
| Region of Enrollment United States | 50 participants | 50 participants | 22 participants | 20 participants | 142 participants |
| Sex: Female, Male Female | 19 Participants | 22 Participants | 9 Participants | 10 Participants | 60 Participants |
| Sex: Female, Male Male | 31 Participants | 28 Participants | 13 Participants | 10 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 | 0 / 22 | 0 / 20 |
| other Total, other adverse events | 11 / 50 | 11 / 50 | 5 / 22 | 4 / 20 |
| serious Total, serious adverse events | 1 / 50 | 0 / 50 | 0 / 22 | 0 / 20 |
Outcome results
Primary
Cigarettes Per Day
Primary objective is to measure a change in cigarette consumption behavior before, during and after switching from usual brand to to VLN cigarettes. Subjects will record their cigarette consumption daily in an electronic diary. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).All 142 randomized subjects were included in the ITT population based on product use. Out of these, 71 subjects were included in the PP Population and 71 were excluded. All excluded subjects had a ratio of \[plasma cotinine/CPD VLN\]/\[plasma cotinine/CPD baseline\] \> 0.2. It was pre-specified to exclude participants with a ratio \>0.2 as they were considered non-compliant.
Time frame: Assessed daily from Week -1 to Week 6; Week -1, Week 2, and Week 6 reported
Population: Cigarettes per Day were calculated as the average cigarettes smoked per day in each week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Cigarettes Per Day | Week 2 | 15.66 Cigarettes Per Day (CPD) | Standard Deviation 7.86 |
| Very Low Nicotine Mentholated | Cigarettes Per Day | Week 6 | 14.43 Cigarettes Per Day (CPD) | Standard Deviation 9.435 |
| Very Low Nicotine Mentholated | Cigarettes Per Day | Week -1 | 14.75 Cigarettes Per Day (CPD) | Standard Deviation 6.198 |
| Very Low Nicotine Non-Mentholated | Cigarettes Per Day | Week 2 | 23.32 Cigarettes Per Day (CPD) | Standard Deviation 9.717 |
| Very Low Nicotine Non-Mentholated | Cigarettes Per Day | Week -1 | 17.19 Cigarettes Per Day (CPD) | Standard Deviation 4.727 |
| Very Low Nicotine Non-Mentholated | Cigarettes Per Day | Week 6 | 21.20 Cigarettes Per Day (CPD) | Standard Deviation 8.219 |
| Very Low Nicotine Combined | Cigarettes Per Day | Week 6 | 17.98 Cigarettes Per Day (CPD) | Standard Deviation 9.265 |
| Very Low Nicotine Combined | Cigarettes Per Day | Week -1 | 15.76 Cigarettes Per Day (CPD) | Standard Deviation 5.676 |
| Very Low Nicotine Combined | Cigarettes Per Day | Week 2 | 18.90 Cigarettes Per Day (CPD) | Standard Deviation 9.341 |
| Usual Brand Mentholated | Cigarettes Per Day | Week 2 | 15.47 Cigarettes Per Day (CPD) | Standard Deviation 4.425 |
| Usual Brand Mentholated | Cigarettes Per Day | Week -1 | 16.29 Cigarettes Per Day (CPD) | Standard Deviation 5.809 |
| Usual Brand Mentholated | Cigarettes Per Day | Week 6 | 14.69 Cigarettes Per Day (CPD) | Standard Deviation 4.877 |
| Usual Brand Non-Mentholated | Cigarettes Per Day | Week 2 | 16.17 Cigarettes Per Day (CPD) | Standard Deviation 4.475 |
| Usual Brand Non-Mentholated | Cigarettes Per Day | Week -1 | 16.80 Cigarettes Per Day (CPD) | Standard Deviation 4.015 |
| Usual Brand Non-Mentholated | Cigarettes Per Day | Week 6 | 15.89 Cigarettes Per Day (CPD) | Standard Deviation 5.356 |
| Usual Brand Combined | Cigarettes Per Day | Week 6 | 15.29 Cigarettes Per Day (CPD) | Standard Deviation 5.092 |
| Usual Brand Combined | Cigarettes Per Day | Week 2 | 15.84 Cigarettes Per Day (CPD) | Standard Deviation 4.411 |
| Usual Brand Combined | Cigarettes Per Day | Week -1 | 16.55 Cigarettes Per Day (CPD) | Standard Deviation 4.895 |
Secondary
Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP)
Total 24 hour urine will be collected to evaluate changes in 1-OHP before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2 and 6 weeks.
Population: Summary of Urinary 1-OHP Mass Excreted (ng/24 hour) by Study Product Group and Study Week (ITT Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week 2 | 262.756 ng/24 hour | Standard Deviation 157.8692 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week -1 | 334.920 ng/24 hour | Standard Deviation 167.7463 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week 6 | 278.998 ng/24 hour | Standard Deviation 178.6065 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week 2 | 214.010 ng/24 hour | Standard Deviation 117.02 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week -1 | 315.203 ng/24 hour | Standard Deviation 160.6678 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week 6 | 203.396 ng/24 hour | Standard Deviation 122.0693 |
| Very Low Nicotine Combined | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week 2 | 239.722 ng/24 hour | Standard Deviation 141.4377 |
| Very Low Nicotine Combined | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week -1 | 324.962 ng/24 hour | Standard Deviation 163.6689 |
| Very Low Nicotine Combined | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week 6 | 241.652 ng/24 hour | Standard Deviation 157.0509 |
| Usual Brand Mentholated | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week 2 | 289.071 ng/24 hour | Standard Deviation 97.7694 |
| Usual Brand Mentholated | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week -1 | 314.736 ng/24 hour | Standard Deviation 90.9545 |
| Usual Brand Mentholated | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week 6 | 299.312 ng/24 hour | Standard Deviation 118.7805 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week 2 | 263.305 ng/24 hour | Standard Deviation 101.9363 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week -1 | 316.566 ng/24 hour | Standard Deviation 140.5579 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week 6 | 274.171 ng/24 hour | Standard Deviation 128.5495 |
| Usual Brand Combined | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week -1 | 315.629 ng/24 hour | Standard Deviation 116.2823 |
| Usual Brand Combined | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week 6 | 286.043 ng/24 hour | Standard Deviation 122.9241 |
| Usual Brand Combined | Biomarkers of Exposure - 1-hydroxy Pyrene(1-OHP) | Week 2 | 276.502 ng/24 hour | Standard Deviation 99.4242 |
Secondary
Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA)
Total 24 hour urine will be collected to evaluate changes in 3-HPMA (acrolein biomarker) before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2 and 6 weeks.
Population: Summary of Urinary 3-HPMA Mass Excreted (µg/24 hour) by Study Product Group and Study Week (ITT Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week 2 | 1706.862 µg/24 hour | Standard Deviation 901.399 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week 6 | 1481.693 µg/24 hour | Standard Deviation 694.6765 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week -1 | 1795.719 µg/24 hour | Standard Deviation 708.6089 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week 2 | 1204.530 µg/24 hour | Standard Deviation 543.2655 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week 6 | 1035.064 µg/24 hour | Standard Deviation 475.3512 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week -1 | 1644.113 µg/24 hour | Standard Deviation 500.1249 |
| Very Low Nicotine Combined | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week 6 | 1261.069 µg/24 hour | Standard Deviation 634.0203 |
| Very Low Nicotine Combined | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week -1 | 1719.151 µg/24 hour | Standard Deviation 613.8453 |
| Very Low Nicotine Combined | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week 2 | 1469.496 µg/24 hour | Standard Deviation 790.9739 |
| Usual Brand Mentholated | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week -1 | 1910.675 µg/24 hour | Standard Deviation 772.7715 |
| Usual Brand Mentholated | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week 2 | 1710.747 µg/24 hour | Standard Deviation 732.7759 |
| Usual Brand Mentholated | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week 6 | 1815.382 µg/24 hour | Standard Deviation 828.3606 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week 6 | 1336.103 µg/24 hour | Standard Deviation 297.2953 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week -1 | 1520.921 µg/24 hour | Standard Deviation 605.248 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week 2 | 1329.844 µg/24 hour | Standard Deviation 319.7909 |
| Usual Brand Combined | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week 2 | 1524.940 µg/24 hour | Standard Deviation 595.158 |
| Usual Brand Combined | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week -1 | 1720.551 µg/24 hour | Standard Deviation 715.1892 |
| Usual Brand Combined | Biomarkers of Exposure - 3-hydroxypropylmercapturic Acid (3-HPMA) | Week 6 | 1562.429 µg/24 hour | Standard Deviation 673.606 |
Secondary
Biomarkers of Exposure - Carboxyhemoglobin (COHb)
Blood will be drawn to evaluate COHb before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: Week -1, and at 2 and 6 weeks.
Population: Summary of Blood COHb (% Saturation) by Study Product Group and Study Week (ITT Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week 2 | 7.10 % Saturation | Standard Deviation 2.794 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week -1 | 6.20 % Saturation | Standard Deviation 1.801 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week 6 | 5.97 % Saturation | Standard Deviation 1.93 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week -1 | 5.69 % Saturation | Standard Deviation 1.526 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week 2 | 5.55 % Saturation | Standard Deviation 2.167 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week 6 | 4.63 % Saturation | Standard Deviation 1.898 |
| Very Low Nicotine Combined | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week -1 | 5.95 % Saturation | Standard Deviation 1.68 |
| Very Low Nicotine Combined | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week 6 | 5.31 % Saturation | Standard Deviation 2.019 |
| Very Low Nicotine Combined | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week 2 | 6.36 % Saturation | Standard Deviation 2.618 |
| Usual Brand Mentholated | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week 2 | 5.40 % Saturation | Standard Deviation 1.206 |
| Usual Brand Mentholated | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week 6 | 5.56 % Saturation | Standard Deviation 1.323 |
| Usual Brand Mentholated | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week -1 | 5.25 % Saturation | Standard Deviation 1.294 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week -1 | 5.41 % Saturation | Standard Deviation 1.322 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week 2 | 5.59 % Saturation | Standard Deviation 2.06 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week 6 | 4.61 % Saturation | Standard Deviation 1.259 |
| Usual Brand Combined | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week 6 | 5.07 % Saturation | Standard Deviation 1.361 |
| Usual Brand Combined | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week -1 | 5.33 % Saturation | Standard Deviation 1.294 |
| Usual Brand Combined | Biomarkers of Exposure - Carboxyhemoglobin (COHb) | Week 2 | 5.49 % Saturation | Standard Deviation 1.659 |
Secondary
Biomarkers of Exposure -Cotinine
Blood will be drawn to evaluate cotinine levels before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per pre-switch Arms/Group assignment.
Time frame: Week -1, and at 2 and 6 weeks.
Population: Blood was drawn to evaluate cotinine levels before, during, and after switching to VLN cigarettes at Week -1, Week 2 and Week 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Biomarkers of Exposure -Cotinine | Week 6 | 102.0 ng/mL | Standard Deviation 76.3105523 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure -Cotinine | Week 2 | 58.8 ng/mL | Standard Deviation 58.5318519 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure -Cotinine | Week 2 | 58.7 ng/mL | Standard Deviation 60.58382526 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure -Cotinine | Week 6 | 110.1 ng/mL | Standard Deviation 102.5119239 |
| Very Low Nicotine Combined | Biomarkers of Exposure -Cotinine | Week 2 | 223.9 ng/mL | Standard Deviation 100.5596713 |
| Very Low Nicotine Combined | Biomarkers of Exposure -Cotinine | Week -1 | 242.0 ng/mL | Standard Deviation 111.1681285 |
| Very Low Nicotine Combined | Biomarkers of Exposure -Cotinine | Week 6 | 207.2 ng/mL | Standard Deviation 81.7796209 |
| Usual Brand Mentholated | Biomarkers of Exposure -Cotinine | Week -1 | 221.4 ng/mL | Standard Deviation 85.32850957 |
| Usual Brand Mentholated | Biomarkers of Exposure -Cotinine | Week 6 | 187.7 ng/mL | Standard Deviation 71.86818497 |
| Usual Brand Mentholated | Biomarkers of Exposure -Cotinine | Week 2 | 195.8 ng/mL | Standard Deviation 77.043868 |
Secondary
Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA)
Total 24 hour urine will be collected to evaluate changes in S-PMA (benzene biomarker) before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2 and 6 weeks.
Population: Summary of Urinary S-PMA Mass Excreted (µg/24 hour) by Study Product Group and Study Week (ITT Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week 2 | 8.160 µg/24 hour | Standard Deviation 7.8142 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week -1 | 7.144 µg/24 hour | Standard Deviation 5.9255 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week 6 | 7.282 µg/24 hour | Standard Deviation 6.435 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week 2 | 6.734 µg/24 hour | Standard Deviation 4.7617 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week -1 | 6.561 µg/24 hour | Standard Deviation 3.8833 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week 6 | 5.589 µg/24 hour | Standard Deviation 3.6334 |
| Very Low Nicotine Combined | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week 2 | 7.486 µg/24 hour | Standard Deviation 6.556 |
| Very Low Nicotine Combined | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week -1 | 6.850 µg/24 hour | Standard Deviation 4.9823 |
| Very Low Nicotine Combined | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week 6 | 6.446 µg/24 hour | Standard Deviation 5.2792 |
| Usual Brand Mentholated | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week 2 | 7.561 µg/24 hour | Standard Deviation 3.7582 |
| Usual Brand Mentholated | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week -1 | 7.935 µg/24 hour | Standard Deviation 3.812 |
| Usual Brand Mentholated | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week 6 | 7.261 µg/24 hour | Standard Deviation 4.4329 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week 2 | 7.731 µg/24 hour | Standard Deviation 5.9223 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week -1 | 8.239 µg/24 hour | Standard Deviation 7.329 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week 6 | 6.845 µg/24 hour | Standard Deviation 5.2829 |
| Usual Brand Combined | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week -1 | 8.083 µg/24 hour | Standard Deviation 5.7274 |
| Usual Brand Combined | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week 6 | 7.042 µg/24 hour | Standard Deviation 4.8353 |
| Usual Brand Combined | Biomarkers of Exposure - S-phenylmercapturic Acid (S-PMA) | Week 2 | 7.644 µg/24 hour | Standard Deviation 4.8713 |
Secondary
Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL)
Total 24 hour urine will be collected to evaluate changes in NNAL (4-methylnitrosamino)-1-3-pyridyl)-1-butanone biomarker) before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2 and 6 weeks.
Population: Summary of Urinary NNAL Mass Excreted (ng/24 hour) by Study Product Group and Study Week (ITT Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week 2 | 313.911 ng/24 hour | Standard Deviation 176.139 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week -1 | 582.855 ng/24 hour | Standard Deviation 288.365 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week 6 | 377.057 ng/24 hour | Standard Deviation 217.6683 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week 2 | 214.139 ng/24 hour | Standard Deviation 131.4077 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week -1 | 423.752 ng/24 hour | Standard Deviation 185.6953 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week 6 | 240.970 ng/24 hour | Standard Deviation 173.1282 |
| Very Low Nicotine Combined | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week 2 | 266.766 ng/24 hour | Standard Deviation 163.6124 |
| Very Low Nicotine Combined | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week -1 | 502.500 ng/24 hour | Standard Deviation 253.6974 |
| Very Low Nicotine Combined | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week 6 | 309.833 ng/24 hour | Standard Deviation 207.3562 |
| Usual Brand Mentholated | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week 2 | 581.039 ng/24 hour | Standard Deviation 312.7864 |
| Usual Brand Mentholated | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week -1 | 614.06 ng/24 hour | Standard Deviation 353.9198 |
| Usual Brand Mentholated | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week 6 | 614.717 ng/24 hour | Standard Deviation 416.6105 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week 2 | 458.036 ng/24 hour | Standard Deviation 203.4045 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week -1 | 479.979 ng/24 hour | Standard Deviation 203.247 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week 6 | 431.458 ng/24 hour | Standard Deviation 173.9915 |
| Usual Brand Combined | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week -1 | 548.658 ng/24 hour | Standard Deviation 294.7134 |
| Usual Brand Combined | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week 6 | 517.997 ng/24 hour | Standard Deviation 321.7481 |
| Usual Brand Combined | Biomarkers of Exposure - Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1 Butanol (NNAL) | Week 2 | 521.037 ng/24 hour | Standard Deviation 269.1556 |
Secondary
Biomarkers of Exposure - Total Nicotine Equivalents
Total 24 hour urine will be collected to evaluate changes in total nicotine equivalents before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2 and 6 weeks.
Population: Summary of Urinary Tneq Mass Excreted (mg/24 hour) by Study Product Group and Study Week (ITT Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Biomarkers of Exposure - Total Nicotine Equivalents | Week 2 | 5.404 mg/24 hour | Standard Deviation 4.5528 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - Total Nicotine Equivalents | Week -1 | 17.511 mg/24 hour | Standard Deviation 6.1103 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - Total Nicotine Equivalents | Week 6 | 9.150 mg/24 hour | Standard Deviation 6.124 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - Total Nicotine Equivalents | Week 2 | 3.616 mg/24 hour | Standard Deviation 3.553 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - Total Nicotine Equivalents | Week -1 | 15.885 mg/24 hour | Standard Deviation 5.3291 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - Total Nicotine Equivalents | Week 6 | 6.800 mg/24 hour | Standard Deviation 5.2118 |
| Very Low Nicotine Combined | Biomarkers of Exposure - Total Nicotine Equivalents | Week 2 | 4.559 mg/24 hour | Standard Deviation 4.1858 |
| Very Low Nicotine Combined | Biomarkers of Exposure - Total Nicotine Equivalents | Week -1 | 16.690 mg/24 hour | Standard Deviation 5.758 |
| Very Low Nicotine Combined | Biomarkers of Exposure - Total Nicotine Equivalents | Week 6 | 7.989 mg/24 hour | Standard Deviation 5.7792 |
| Usual Brand Mentholated | Biomarkers of Exposure - Total Nicotine Equivalents | Week 2 | 16.962 mg/24 hour | Standard Deviation 6.2675 |
| Usual Brand Mentholated | Biomarkers of Exposure - Total Nicotine Equivalents | Week -1 | 17.732 mg/24 hour | Standard Deviation 6.3013 |
| Usual Brand Mentholated | Biomarkers of Exposure - Total Nicotine Equivalents | Week 6 | 17.530 mg/24 hour | Standard Deviation 7.3994 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - Total Nicotine Equivalents | Week 2 | 15.279 mg/24 hour | Standard Deviation 4.7106 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - Total Nicotine Equivalents | Week -1 | 15.928 mg/24 hour | Standard Deviation 5.9611 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - Total Nicotine Equivalents | Week 6 | 14.418 mg/24 hour | Standard Deviation 5.5176 |
| Usual Brand Combined | Biomarkers of Exposure - Total Nicotine Equivalents | Week -1 | 16.852 mg/24 hour | Standard Deviation 6.1291 |
| Usual Brand Combined | Biomarkers of Exposure - Total Nicotine Equivalents | Week 6 | 15.888 mg/24 hour | Standard Deviation 6.5703 |
| Usual Brand Combined | Biomarkers of Exposure - Total Nicotine Equivalents | Week 2 | 16.141 mg/24 hour | Standard Deviation 5.5594 |
Secondary
Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN)
Total 24 hour urine will be collected to evaluate changes in NNN before, during, and after switching to VLN cigarettes. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2 and 6 weeks.
Population: Summary of Urinary NNAL Mass Excreted (ng/24 hour) by Study Product Group and Study Week (ITT Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week 2 | 14.246 ng/24 hour | Standard Deviation 11.6548 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week -1 | 20.070 ng/24 hour | Standard Deviation 14.4934 |
| Very Low Nicotine Mentholated | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week 6 | 14.803 ng/24 hour | Standard Deviation 11.4754 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week 2 | 9.052 ng/24 hour | Standard Deviation 10.2762 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week -1 | 12.370 ng/24 hour | Standard Deviation 7.9412 |
| Very Low Nicotine Non-Mentholated | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week 6 | 6.382 ng/24 hour | Standard Deviation 4.5544 |
| Very Low Nicotine Combined | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week 2 | 11.792 ng/24 hour | Standard Deviation 11.2701 |
| Very Low Nicotine Combined | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week -1 | 16.181 ng/24 hour | Standard Deviation 12.2224 |
| Very Low Nicotine Combined | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week 6 | 10.643 ng/24 hour | Standard Deviation 9.6904 |
| Usual Brand Mentholated | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week 2 | 20.809 ng/24 hour | Standard Deviation 21.2301 |
| Usual Brand Mentholated | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week -1 | 22.614 ng/24 hour | Standard Deviation 24.4627 |
| Usual Brand Mentholated | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week 6 | 22.095 ng/24 hour | Standard Deviation 25.7769 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week 2 | 12.024 ng/24 hour | Standard Deviation 9.0103 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week -1 | 13.641 ng/24 hour | Standard Deviation 11.1026 |
| Usual Brand Non-Mentholated | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week 6 | 9.359 ng/24 hour | Standard Deviation 6.0602 |
| Usual Brand Combined | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week -1 | 18.237 ng/24 hour | Standard Deviation 19.4522 |
| Usual Brand Combined | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week 6 | 15.373 ng/24 hour | Standard Deviation 19.0844 |
| Usual Brand Combined | Biomarkers of Exposure - Total N-Nitrosonornicotine (NNN) | Week 2 | 16.523 ng/24 hour | Standard Deviation 16.843 |
Secondary
Nicotine Pharmacokinetics - Area Under Nicotine Concentration Curve (AUC)
Blood samples will be drawn at -5, 2, 5, 7, 10, 12, 15, 20, 30, 45, 60, 90, 120, 150 and 180 minutes relative to the start of cigarette smoking a single cigarette for determination of AUC at weeks -1, 2 and 6. The baseline data were collected for participants at Week -1, and Week -1 data are reported per pre-switch Arms/Group assignment.
Time frame: Week -1, and at 2 and 6 weeks.
Population: Plasma Nicotine Pharmacokinetic Parameters (AUC0-180) Following Use of VLN Non-Mentholated, VLN Mentholated, UB Mentholated and UB Non-Mentholated Filtered Cigarettes (Pharmacokinetic Population from ITT).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Nicotine Pharmacokinetics - Area Under Nicotine Concentration Curve (AUC) | Week 2 | 0.2006 mg*hr/mL | Standard Deviation 0.19107 |
| Very Low Nicotine Mentholated | Nicotine Pharmacokinetics - Area Under Nicotine Concentration Curve (AUC) | Week 6 | 0.2620 mg*hr/mL | Standard Deviation 0.15446 |
| Very Low Nicotine Non-Mentholated | Nicotine Pharmacokinetics - Area Under Nicotine Concentration Curve (AUC) | Week 2 | 0.2264 mg*hr/mL | Standard Deviation 0.20588 |
| Very Low Nicotine Non-Mentholated | Nicotine Pharmacokinetics - Area Under Nicotine Concentration Curve (AUC) | Week 6 | 0.2348 mg*hr/mL | Standard Deviation 0.2033 |
| Very Low Nicotine Combined | Nicotine Pharmacokinetics - Area Under Nicotine Concentration Curve (AUC) | Week -1 | 13.60 mg*hr/mL | Standard Deviation 5.261 |
| Usual Brand Mentholated | Nicotine Pharmacokinetics - Area Under Nicotine Concentration Curve (AUC) | Week -1 | 13.18 mg*hr/mL | Standard Deviation 4.0648 |
Secondary
Nicotine Pharmacokinetics - Maximum Nicotine Concentration (C-Max)
Blood samples will be drawn at -5, 2, 5, 7, 10, 12, 15, 20, 30, 45, 60, 90, 120, 150 and 180 minutes relative to the start of cigarette smoking a single cigarette for determination of C-max at weeks -1, 2 and 6. The baseline data were collected for participants at Week -1, and Week -1 data are reported per pre-switch Arms/Group assignment.
Time frame: Week -1, and at 2 and 6 weeks.
Population: Plasma Nicotine Pharmacokinetic Parameters (Cmax) Following use of VLN Non-Mentholated, VLN Mentholated, UB Non-Mentholated, UB Mentholated Cigarettes (Pharmacokinetic Population from ITT).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Nicotine Pharmacokinetics - Maximum Nicotine Concentration (C-Max) | Week 2 | 0.3264 ng/mL | Standard Deviation 0.15367 |
| Very Low Nicotine Mentholated | Nicotine Pharmacokinetics - Maximum Nicotine Concentration (C-Max) | Week 6 | 0.4026 ng/mL | Standard Deviation 0.15292 |
| Very Low Nicotine Non-Mentholated | Nicotine Pharmacokinetics - Maximum Nicotine Concentration (C-Max) | Week 2 | 0.3561 ng/mL | Standard Deviation 0.20204 |
| Very Low Nicotine Non-Mentholated | Nicotine Pharmacokinetics - Maximum Nicotine Concentration (C-Max) | Week 6 | 0.3259 ng/mL | Standard Deviation 0.16294 |
| Very Low Nicotine Combined | Nicotine Pharmacokinetics - Maximum Nicotine Concentration (C-Max) | Week -1 | 13.28 ng/mL | Standard Deviation 5.9925 |
| Usual Brand Mentholated | Nicotine Pharmacokinetics - Maximum Nicotine Concentration (C-Max) | Week -1 | 12.98 ng/mL | Standard Deviation 5.3932 |
Secondary
Nicotine Pharmacokinetics - Peak Nicotine Time (T-Max)
Blood samples will be drawn at -5, 2, 5, 7, 10, 12, 15, 20, 30, 45, 60, 90, 120, 150 and 180 minutes relative to the start of cigarette smoking a single cigarette for determination of T-Max at weeks -1, 2 and 6. The baseline data were collected for participants at Week -1, and Week -1 data are reported per pre-switch Arms/Group assignment.
Time frame: Week -1, and at 2 and 6 weeks.
Population: Plasma Nicotine Pharmacokinetic Parameters (Tmax) Following Use of VLN Non-Mentholated, VLN Mentholated, UB Mentholated and UB Non-Mentholated Cigarettes (Pharmacokinetic Population from ITT).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Nicotine Pharmacokinetics - Peak Nicotine Time (T-Max) | Week 2 | 0.1154 hr | Standard Deviation 0.040675 |
| Very Low Nicotine Mentholated | Nicotine Pharmacokinetics - Peak Nicotine Time (T-Max) | Week 6 | 0.1446 hr | Standard Deviation 0.084195 |
| Very Low Nicotine Non-Mentholated | Nicotine Pharmacokinetics - Peak Nicotine Time (T-Max) | Week 2 | 0.1430 hr | Standard Deviation 0.063681 |
| Very Low Nicotine Non-Mentholated | Nicotine Pharmacokinetics - Peak Nicotine Time (T-Max) | Week 6 | 0.2895 hr | Standard Deviation 0.43017 |
| Very Low Nicotine Combined | Nicotine Pharmacokinetics - Peak Nicotine Time (T-Max) | Week -1 | 13.60 hr | Standard Deviation 5.261 |
| Usual Brand Mentholated | Nicotine Pharmacokinetics - Peak Nicotine Time (T-Max) | Week -1 | 0.1408 hr | Standard Deviation 0.041525 |
Secondary
Smoking Topography - Average Flow Rate
Average Puff Flow Rate will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2 and 6 weeks.
Population: Summary of Puffing Topography Parameters by Study Product Group and Study Week (ITT Population). Puff topography was conducted in a randomly-selected subset of 18 non-menthol and 18 menthol cigarette smokers at a single site. The randomly-selected subjects have been assigned to switch to smoking very low nicotine (VLN) cigarettes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Smoking Topography - Average Flow Rate | Week 2 | 23.6309 mL/sec | Standard Deviation 7.84344 |
| Very Low Nicotine Mentholated | Smoking Topography - Average Flow Rate | Week -1 | 27.8305 mL/sec | Standard Deviation 8.55885 |
| Very Low Nicotine Mentholated | Smoking Topography - Average Flow Rate | Week 6 | 26.7164 mL/sec | Standard Deviation 9.72496 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Average Flow Rate | Week 2 | 25.4534 mL/sec | Standard Deviation 5.68677 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Average Flow Rate | Week -1 | 28.5428 mL/sec | Standard Deviation 12.99509 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Average Flow Rate | Week 6 | 24.1247 mL/sec | Standard Deviation 5.15403 |
| Very Low Nicotine Combined | Smoking Topography - Average Flow Rate | Week -1 | 28.1866 mL/sec | Standard Deviation 10.85056 |
| Very Low Nicotine Combined | Smoking Topography - Average Flow Rate | Week 6 | 25.5016 mL/sec | Standard Deviation 7.90798 |
| Very Low Nicotine Combined | Smoking Topography - Average Flow Rate | Week 2 | 24.5698 mL/sec | Standard Deviation 6.77219 |
Secondary
Smoking Topography - Inter-puff Interval
Inter-puff interval will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2 and 6 weeks.
Population: Summary of Puffing Topography Parameters by Study Product Group and Study Week (ITT Population). Puff topography was conducted in a randomly-selected subset of 18 non-menthol and 18 menthol cigarette smokers at a single site. The randomly-selected subjects have been assigned to switch to smoking very low nicotine (VLN) cigarettes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Smoking Topography - Inter-puff Interval | Week 2 | 24.280 sec | Standard Deviation 9.2227 |
| Very Low Nicotine Mentholated | Smoking Topography - Inter-puff Interval | Week -1 | 30.269 sec | Standard Deviation 10.205 |
| Very Low Nicotine Mentholated | Smoking Topography - Inter-puff Interval | Week 6 | 21.044 sec | Standard Deviation 7.181 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Inter-puff Interval | Week 2 | 26.624 sec | Standard Deviation 12.1134 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Inter-puff Interval | Week -1 | 29.222 sec | Standard Deviation 8.2654 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Inter-puff Interval | Week 6 | 27.215 sec | Standard Deviation 11.4332 |
| Very Low Nicotine Combined | Smoking Topography - Inter-puff Interval | Week -1 | 29.746 sec | Standard Deviation 9.1677 |
| Very Low Nicotine Combined | Smoking Topography - Inter-puff Interval | Week 6 | 23.937 sec | Standard Deviation 9.7693 |
| Very Low Nicotine Combined | Smoking Topography - Inter-puff Interval | Week 2 | 25.488 sec | Standard Deviation 10.7076 |
Secondary
Smoking Topography - Peak Puff Flow Rate
Peak Puff Flow Rate will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2 and 6 weeks.
Population: Summary of Puffing Topography Parameters by Study Product Group and Study Week (ITT Population). Puff topography was conducted in a randomly-selected subset of 18 non-menthol and 18 menthol cigarette smokers at a single site. The randomly-selected subjects have been assigned to switch to smoking very low nicotine (VLN) cigarettes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Smoking Topography - Peak Puff Flow Rate | Week 2 | 39.7010 mL/sec | Standard Deviation 13.72368 |
| Very Low Nicotine Mentholated | Smoking Topography - Peak Puff Flow Rate | Week -1 | 44.3213 mL/sec | Standard Deviation 10.85319 |
| Very Low Nicotine Mentholated | Smoking Topography - Peak Puff Flow Rate | Week 6 | 43.4274 mL/sec | Standard Deviation 14.75467 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Peak Puff Flow Rate | Week 2 | 41.4412 mL/sec | Standard Deviation 9.94555 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Peak Puff Flow Rate | Week -1 | 45.9639 mL/sec | Standard Deviation 20.10163 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Peak Puff Flow Rate | Week 6 | 40.0195 mL/sec | Standard Deviation 9.05336 |
| Very Low Nicotine Combined | Smoking Topography - Peak Puff Flow Rate | Week -1 | 45.1426 mL/sec | Standard Deviation 15.94278 |
| Very Low Nicotine Combined | Smoking Topography - Peak Puff Flow Rate | Week 6 | 41.8300 mL/sec | Standard Deviation 12.34352 |
| Very Low Nicotine Combined | Smoking Topography - Peak Puff Flow Rate | Week 2 | 40.5975 mL/sec | Standard Deviation 11.7695 |
Secondary
Smoking Topography - Puff Duration
Puff duration will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2 and 6 weeks.
Population: Summary of Puffing Topography Parameters by Study Product Group and Study Week (ITT Population). Puff topography was conducted in a randomly-selected subset of 18 non-menthol and 18 menthol cigarette smokers at a single site. The randomly-selected subjects have been assigned to switch to smoking very low nicotine (VLN) cigarettes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Smoking Topography - Puff Duration | Week -1 | 23.494 seconds | Standard Deviation 7.9301 |
| Very Low Nicotine Mentholated | Smoking Topography - Puff Duration | Week 6 | 21.966 seconds | Standard Deviation 7.0242 |
| Very Low Nicotine Mentholated | Smoking Topography - Puff Duration | Week 2 | 23.282 seconds | Standard Deviation 8.1071 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Puff Duration | Week 2 | 24.559 seconds | Standard Deviation 6.9773 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Puff Duration | Week -1 | 27.783 seconds | Standard Deviation 7.6979 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Puff Duration | Week 6 | 22.122 seconds | Standard Deviation 6.4746 |
| Very Low Nicotine Combined | Smoking Topography - Puff Duration | Week -1 | 25.639 seconds | Standard Deviation 8.0036 |
| Very Low Nicotine Combined | Smoking Topography - Puff Duration | Week 6 | 22.039 seconds | Standard Deviation 6.6636 |
| Very Low Nicotine Combined | Smoking Topography - Puff Duration | Week 2 | 23.940 seconds | Standard Deviation 7.4545 |
Secondary
Smoking Topography - Puff Volume
Puff volume will be measured before, during, and after switching to VLN cigarettes. Topography will be measured during an ad libitum smoking session. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2 and 6 weeks.
Population: Summary of Puffing Topography Parameters by Study Product Group and Study Week (ITT Population). Puff topography was conducted in a randomly-selected subset of 18 non-menthol and 18 menthol cigarette smokers at a single site. The randomly-selected subjects have been assigned to switch to smoking very low nicotine (VLN) cigarettes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Smoking Topography - Puff Volume | Week -1 | 50.7496 mL | Standard Deviation 12.88508 |
| Very Low Nicotine Mentholated | Smoking Topography - Puff Volume | Week 2 | 44.6595 mL | Standard Deviation 13.48557 |
| Very Low Nicotine Mentholated | Smoking Topography - Puff Volume | Week 6 | 47.9733 mL | Standard Deviation 13.25475 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Puff Volume | Week 6 | 46.7513 mL | Standard Deviation 11.6315 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Puff Volume | Week 2 | 49.7368 mL | Standard Deviation 13.17315 |
| Very Low Nicotine Non-Mentholated | Smoking Topography - Puff Volume | Week -1 | 57.8934 mL | Standard Deviation 23.65244 |
| Very Low Nicotine Combined | Smoking Topography - Puff Volume | Week -1 | 54.3215 mL | Standard Deviation 19.11782 |
| Very Low Nicotine Combined | Smoking Topography - Puff Volume | Week 2 | 47.2751 mL | Standard Deviation 13.36612 |
| Very Low Nicotine Combined | Smoking Topography - Puff Volume | Week 6 | 47.4005 mL | Standard Deviation 12.33536 |
Secondary
Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief)
Subjects will answer a Brief Questionnaire of Smoking Urges (QSU-Brief). QSU is on a scale of 1-7, with 1 being strongly disagree and 7 being strongly agree. The average score of the following is taken to determine the Factor Score 1 and Factor Score 2; Factor 1: Average of Questions 1, 3, 6, 7, and 10; Factor 2: Average of Questions 2, 4, 5, 8, and 9. The score for each factor is calculated by summing the item scores; the total score is calculated by summing all questions together. The higher the score, the greater the urge to smoke. The total score range for this questionnaire is 10-70. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: Week -1, and at 2, 4, and 6 weeks.
Population: Summary of QSU-Brief Factor Score by Study Product Group and Study Week (ITT Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week -1 | 4.2 score on a scale | Standard Deviation 1.68 |
| Very Low Nicotine Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 2 | 3.7 score on a scale | Standard Deviation 1.87 |
| Very Low Nicotine Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 4 | 3.8 score on a scale | Standard Deviation 1.68 |
| Very Low Nicotine Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 6 | 3.4 score on a scale | Standard Deviation 1.7 |
| Very Low Nicotine Non-Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 4 | 3.9 score on a scale | Standard Deviation 1.47 |
| Very Low Nicotine Non-Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week -1 | 4.3 score on a scale | Standard Deviation 1.7 |
| Very Low Nicotine Non-Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 6 | 4.4 score on a scale | Standard Deviation 1.68 |
| Very Low Nicotine Non-Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 2 | 5.4 score on a scale | Standard Deviation 1.5 |
| Very Low Nicotine Combined | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week -1 | 4.3 score on a scale | Standard Deviation 1.69 |
| Very Low Nicotine Combined | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 6 | 3.9 score on a scale | Standard Deviation 1.75 |
| Very Low Nicotine Combined | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 2 | 4.5 score on a scale | Standard Deviation 1.88 |
| Very Low Nicotine Combined | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 4 | 3.8 score on a scale | Standard Deviation 1.56 |
| Usual Brand Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week -1 | 4.51 score on a scale | Standard Deviation 1.5 |
| Usual Brand Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 2 | 4.3 score on a scale | Standard Deviation 1.74 |
| Usual Brand Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 6 | 4.1 score on a scale | Standard Deviation 1.57 |
| Usual Brand Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 4 | 3.8 score on a scale | Standard Deviation 1.47 |
| Usual Brand Non-Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week -1 | 3.8 score on a scale | Standard Deviation 1.26 |
| Usual Brand Non-Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 6 | 3.5 score on a scale | Standard Deviation 1.57 |
| Usual Brand Non-Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 2 | 3.7 score on a scale | Standard Deviation 1.48 |
| Usual Brand Non-Mentholated | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 4 | 3.7 score on a scale | Standard Deviation 1.42 |
| Usual Brand Combined | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 4 | 3.7 score on a scale | Standard Deviation 1.43 |
| Usual Brand Combined | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 2 | 4.0 score on a scale | Standard Deviation 1.61 |
| Usual Brand Combined | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week -1 | 4.1 score on a scale | Standard Deviation 1.41 |
| Usual Brand Combined | Subjective Effects -Brief Questionnaire of Smoking Urges (QSU-Brief) | Week 6 | 3.8 score on a scale | Standard Deviation 1.57 |
Secondary
Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD)
Subjects will answer a Fagerstrom Test for Cigarette Dependance (FTCD) questionnaire which contains six items that evaluate the quantity of cigarette consumption, the compulsion to use, and dependence.The Fagerstrom Test for Nicotine Dependence, is scored from 0 to 1 for yes/no items and 0 to 3 for multiple-choice items.The items are summed to yield a total score of 0-10. The higher the total Fagerström score, the greater the patient's physical dependence on nicotine. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2, 4, and 6 weeks.
Population: Summary of FTCD Score by Study Product Group and Study Week (ITT Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 2 | 5.0 score on a scale | Standard Deviation 1.79 |
| Very Low Nicotine Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week -1 | 5.2 score on a scale | Standard Deviation 1.6 |
| Very Low Nicotine Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 4 | 4.8 score on a scale | Standard Deviation 1.44 |
| Very Low Nicotine Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 6 | 4.7 score on a scale | Standard Deviation 1.65 |
| Very Low Nicotine Non-Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 6 | 6.0 score on a scale | Standard Deviation 1.68 |
| Very Low Nicotine Non-Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 2 | 6.3 score on a scale | Standard Deviation 1.61 |
| Very Low Nicotine Non-Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week -1 | 6.0 score on a scale | Standard Deviation 1.53 |
| Very Low Nicotine Non-Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 4 | 6.3 score on a scale | Standard Deviation 1.71 |
| Very Low Nicotine Combined | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 2 | 5.7 score on a scale | Standard Deviation 1.81 |
| Very Low Nicotine Combined | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week -1 | 5.6 score on a scale | Standard Deviation 1.61 |
| Very Low Nicotine Combined | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 6 | 5.4 score on a scale | Standard Deviation 1.78 |
| Very Low Nicotine Combined | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 4 | 5.6 score on a scale | Standard Deviation 1.76 |
| Usual Brand Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 2 | 5.2 score on a scale | Standard Deviation 1.87 |
| Usual Brand Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week -1 | 5.2 score on a scale | Standard Deviation 1.46 |
| Usual Brand Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 6 | 5.4 score on a scale | Standard Deviation 1.98 |
| Usual Brand Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 4 | 5.3 score on a scale | Standard Deviation 2.02 |
| Usual Brand Non-Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 2 | 4.9 score on a scale | Standard Deviation 1.92 |
| Usual Brand Non-Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week -1 | 5.4 score on a scale | Standard Deviation 1.73 |
| Usual Brand Non-Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 4 | 5.3 score on a scale | Standard Deviation 1.85 |
| Usual Brand Non-Mentholated | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 6 | 5.2 score on a scale | Standard Deviation 2.04 |
| Usual Brand Combined | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 6 | 5.3 score on a scale | Standard Deviation 1.99 |
| Usual Brand Combined | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week -1 | 5.3 score on a scale | Standard Deviation 1.59 |
| Usual Brand Combined | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 2 | 5.1 score on a scale | Standard Deviation 1.88 |
| Usual Brand Combined | Subjective Effects -Fagerstrom Test for Cigarette Dependance (FTCD) | Week 4 | 5.3 score on a scale | Standard Deviation 1.92 |
Secondary
Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R)
Subjects will answer a MNWS-R questionnaire. The MNWS is considered as the briefest scale among the self-report measures of nicotine withdrawal symptoms currently available. The original MNWS was developed by Hughes and Hatsukami in 1986. It consisted of nine nicotine withdrawal symptoms including craving. The scale was modified to reflect changes made in the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for nicotine withdrawal. The total score of the scale range from 0 to 36 depending on participant's rate for the symptoms as not present (0), slight (1), mild (2), moderate (3), and severe (4). A high total score implies high nicotine addiction. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2, 4, and 6 weeks.
Population: Summary of MNWS-R Total Score by Study Product Group and Study Week (ITT Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 6 | 5.4 score on a scale | Standard Deviation 6.17 |
| Very Low Nicotine Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 4 | 6.5 score on a scale | Standard Deviation 7.67 |
| Very Low Nicotine Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week -1 | 8.1 score on a scale | Standard Deviation 7.56 |
| Very Low Nicotine Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 2 | 8.4 score on a scale | Standard Deviation 8.53 |
| Very Low Nicotine Non-Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week -1 | 13.0 score on a scale | Standard Deviation 8.77 |
| Very Low Nicotine Non-Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 2 | 16.0 score on a scale | Standard Deviation 9.74 |
| Very Low Nicotine Non-Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 6 | 13.4 score on a scale | Standard Deviation 10.01 |
| Very Low Nicotine Non-Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 4 | 13.5 score on a scale | Standard Deviation 10.55 |
| Very Low Nicotine Combined | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 6 | 9.5 score on a scale | Standard Deviation 9.22 |
| Very Low Nicotine Combined | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week -1 | 10.6 score on a scale | Standard Deviation 8.52 |
| Very Low Nicotine Combined | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 2 | 12.3 score on a scale | Standard Deviation 9.88 |
| Very Low Nicotine Combined | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 4 | 10.1 score on a scale | Standard Deviation 9.86 |
| Usual Brand Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 4 | 8.4 score on a scale | Standard Deviation 8.76 |
| Usual Brand Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week -1 | 10.6 score on a scale | Standard Deviation 9.68 |
| Usual Brand Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 2 | 8.1 score on a scale | Standard Deviation 9.02 |
| Usual Brand Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 6 | 7.5 score on a scale | Standard Deviation 7.32 |
| Usual Brand Non-Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 2 | 9.0 score on a scale | Standard Deviation 6.94 |
| Usual Brand Non-Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week -1 | 9.2 score on a scale | Standard Deviation 7.49 |
| Usual Brand Non-Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 6 | 8.3 score on a scale | Standard Deviation 7.53 |
| Usual Brand Non-Mentholated | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 4 | 7.8 score on a scale | Standard Deviation 7.1 |
| Usual Brand Combined | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 6 | 7.9 score on a scale | Standard Deviation 7.33 |
| Usual Brand Combined | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week -1 | 9.9 score on a scale | Standard Deviation 8.52 |
| Usual Brand Combined | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 2 | 8.6 score on a scale | Standard Deviation 7.9 |
| Usual Brand Combined | Subjective Effects - Minnesota Nicotine Withdrawal Scale - Revised (MNWS-R) | Week 4 | 8.1 score on a scale | Standard Deviation 7.89 |
Secondary
Subjective Effects - Perceived Health Risks
Subjects will answer a Perceived health risks questionnaire. The subjects indicated their perception of the risk of becoming addicted to the cigarette they were currently using on a scale from 1 to 10. Scale =1 was a very low risk of becoming addicted and Scale =10 was a very high risk of becoming addicted. The baseline data were collected for participants at Week -1, and Week -1 data are reported per post-switch Arms/Group randomization (instead of pre-switch Arms/Group assignment).
Time frame: -1 week, and at 2, 4, and 6 weeks.
Population: Summary of Perceived Health Risk Scale by Study Product Group and Study Week (ITT Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Very Low Nicotine Mentholated | Subjective Effects - Perceived Health Risks | Week -1 | 7.0 units on a scale | Standard Deviation 2.17 |
| Very Low Nicotine Mentholated | Subjective Effects - Perceived Health Risks | Week 6 | 3.2 units on a scale | Standard Deviation 2.89 |
| Very Low Nicotine Mentholated | Subjective Effects - Perceived Health Risks | Week 4 | 3.4 units on a scale | Standard Deviation 2.86 |
| Very Low Nicotine Mentholated | Subjective Effects - Perceived Health Risks | Week 2 | 3.4 units on a scale | Standard Deviation 2.73 |
| Very Low Nicotine Non-Mentholated | Subjective Effects - Perceived Health Risks | Week 6 | 3.6 units on a scale | Standard Deviation 2.79 |
| Very Low Nicotine Non-Mentholated | Subjective Effects - Perceived Health Risks | Week 2 | 4.0 units on a scale | Standard Deviation 3.02 |
| Very Low Nicotine Non-Mentholated | Subjective Effects - Perceived Health Risks | Week -1 | 7.6 units on a scale | Standard Deviation 2.04 |
| Very Low Nicotine Non-Mentholated | Subjective Effects - Perceived Health Risks | Week 4 | 3.4 units on a scale | Standard Deviation 2.55 |
| Very Low Nicotine Combined | Subjective Effects - Perceived Health Risks | Week 4 | 34 units on a scale | Standard Deviation 2.69 |
| Very Low Nicotine Combined | Subjective Effects - Perceived Health Risks | Week 2 | 3.7 units on a scale | Standard Deviation 2.88 |
| Very Low Nicotine Combined | Subjective Effects - Perceived Health Risks | Week -1 | 7.3 units on a scale | Standard Deviation 2.12 |
| Very Low Nicotine Combined | Subjective Effects - Perceived Health Risks | Week 6 | 3.4 units on a scale | Standard Deviation 2.83 |
| Usual Brand Mentholated | Subjective Effects - Perceived Health Risks | Week 4 | 6.7 units on a scale | Standard Deviation 2.37 |
| Usual Brand Mentholated | Subjective Effects - Perceived Health Risks | Week 2 | 6.8 units on a scale | Standard Deviation 2.07 |
| Usual Brand Mentholated | Subjective Effects - Perceived Health Risks | Week -1 | 6.6 units on a scale | Standard Deviation 2.09 |
| Usual Brand Mentholated | Subjective Effects - Perceived Health Risks | Week 6 | 6.6 units on a scale | Standard Deviation 1.7 |
| Usual Brand Non-Mentholated | Subjective Effects - Perceived Health Risks | Week 6 | 6.9 units on a scale | Standard Deviation 2.54 |
| Usual Brand Non-Mentholated | Subjective Effects - Perceived Health Risks | Week 2 | 7.0 units on a scale | Standard Deviation 2.68 |
| Usual Brand Non-Mentholated | Subjective Effects - Perceived Health Risks | Week -1 | 7.7 units on a scale | Standard Deviation 2.25 |
| Usual Brand Non-Mentholated | Subjective Effects - Perceived Health Risks | Week 4 | 7.4 units on a scale | Standard Deviation 2.55 |
| Usual Brand Combined | Subjective Effects - Perceived Health Risks | Week 6 | 6.7 units on a scale | Standard Deviation 2.12 |
| Usual Brand Combined | Subjective Effects - Perceived Health Risks | Week -1 | 7.1 units on a scale | Standard Deviation 2.23 |
| Usual Brand Combined | Subjective Effects - Perceived Health Risks | Week 2 | 6.9 units on a scale | Standard Deviation 2.38 |
| Usual Brand Combined | Subjective Effects - Perceived Health Risks | Week 4 | 7.0 units on a scale | Standard Deviation 2.45 |