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| ID | Type | Description | Link |
|---|---|---|---|
| U01DA020830 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
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The purpose of this research program is to understand how a biomarker called the "nicotine metabolite ratio" (also referred to as NMR) may influence a smoker's ability to quit smoking.
Smoking is an enormous public health problem with a great need for research to improve treatment outcomes. Our prior data indicates that the cytochrome P450 2A6 (CYP2A6) enzyme is critical in the metabolic inactivation of nicotine, and also influences smoking behavior and response to therapies. With a vision toward translation of our research to practice, we have characterized a genetically-informed biomarker of CYP2A6 activity, specifically the nicotine metabolite ratio (NMR; 3'hydroxycotinine/cotinine), which reflects both CYP2A6 genetic variation and environmental influences on CYP2A6 activity. The NMR is measured non-invasively in smokers with established reliability, stability, analytic validity, and efficacy as a predictor of the ability to quit smoking and treatment response in multiple retrospective trials. Translation of these findings to clinical practice requires validation in a prospective clinical trial comparing alternative therapies for smoking cessation. Thus, the proposed trial is a prospective, stratified, placebo-controlled, multi-center clinical trial of alternative therapies for smoking cessation treatment in approximately 1,200 smokers. Randomization to placebo (PLA), transdermal nicotine (TN), or varenicline (VAR) will be stratified prospectively based on the nicotine metabolite ratio (NMR). Abstinence from smoking at the end of treatment will be the primary outcome. Quit rate at 6-month follow-up is a secondary outcome. To facilitate translation to practice, analysis of the cost-effectiveness of our proposed approach will also be completed. The proposed research provides the next critical step to validate a genetically-informed diagnostic tool, the NMR, which clinicians can use in the future to optimize treatment decisions for their patients who wish to quit smoking.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo (Slow Metabolizers) | Placebo Comparator | Subjects in this arm are those identified as slow metabolizers of nicotine (based on their NMR) and will take placebo pills daily for twelve weeks & wear a placebo patch daily for eleven weeks. The placebo pill will look identical to the active varenicline tablets; however, they will not contain any active medication. Subjects will follow the same drug regimen as those in the active varenicline arm. The placebo patch will look identical to the active transdermal nicotine patches; however, they do not contain actual nicotine. Subjects will follow the same regimen as those in the active transdermal nicotine arm. All subjects in this arm will receive smoking cessation counseling during their sessions. |
|
| Varenicline (Slow Metabolizers) | Active Comparator | Subjects in this arm are those identified as slow metabolizers of nicotine (based on their NMR) and will take active varenicline pills daily for twelve weeks & wear a placebo patch daily for eleven weeks. When taking the active varenicline, subjects will follow the same treatment regimen per the manufacturer. The placebo patch will look identical to the active transdermal nicotine patches; however, they do not contain actual nicotine. Subjects will follow the same regimen as those in the active transdermal nicotine arm. All subjects in this arm will receive smoking cessation counseling during their sessions. |
|
| Transdermal Nicotine (Slow Metabolizers) | Active Comparator | Subjects in this arm are those identified as slow metabolizers of nicotine (based on their NMR) and will take placebo pills daily for twelve weeks & will wear an active transdermal nicotine patch daily for eleven weeks. The placebo pill will look identical to the active varenicline tablets; however, they will not contain any active medication. Subjects will follow the same drug regimen as those in the active varenicline arm. When wearing the active transdermal nicotine, subjects will follow the same treatment regimen per the manufacturer. All subjects in this arm will receive smoking cessation counseling during their sessions. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Varenicline | Drug | Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| 7-day Point Prevalence Quit Rate at End-of-Treatment (EOT) | The percentage of ITT subjects who were verified as abstinent. Abstinence was defined as no self-reported smoking (not even a puff) for at least 7 days before the telephone assessment, with in-person verification for those self-reporting abstinence. In-person verification consisted of breath carbon monoxide analysis, with a reading of 8 parts-per-million or less confirming abstinence. Subjects who were lost to follow-up were considered smokers. | Week 11 |
| Measure | Description | Time Frame |
|---|---|---|
| 7-day Point Prevalence Quit Rate at 6-month Follow up Survey | The percentage of ITT subjects who were verified as abstinent at the 6-month follow up survey. Abstinence was defined as no self-reported smoking (not even a puff) for at least 7 days before the telephone assessment, with in-person verification for those self-reporting abstinence. In-person verification consisted of breath carbon monoxide analysis, with a reading of 8 parts-per-million or less confirming abstinence. Subjects who were lost to follow-up were considered smokers. |
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Inclusion Criteria:
Eligible participants will be males and females
Exclusion Criteria:
Smoking Behavior
Alcohol/Drug Exclusion Criteria
Medical Exclusion Criteria
Women who are pregnant, planning a pregnancy, or lactating.
History of epilepsy or a seizure disorder.
Current medical problems for which transdermal nicotine is contraindicated including:
Serious or unstable disease within the past 6 months.
History (last 6 months) of abnormal heart rhythms, tachycardia and cardiovascular disease (stroke, angina, heart attack) may result in ineligibility. These conditions will be evaluated on a case by case basis by the Study Physician.
Inability to provide a blood sample to be used to assess nicotine metabolite ratio.
Psychiatric Exclusion Criteria (as determined by self report & MINI)
Medication Exclusion Criteria
Current use or recent discontinuation (within the last 14-days) of:
Current use of:
Daily use of:
General Exclusion
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| Name | Affiliation | Role |
|---|---|---|
| Caryn Lerman, PhD | University of Pennsylvania | Principal Investigator |
| Rachel F Tyndale, PhD | University of Toronto | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University at Buffalo - State University of New York | Buffalo | New York | 14260 | United States | ||
| Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40358028 | Derived | Tonkin SS, Betts JM, Dowd AN, Mahoney MC, Cinciripini PM, Schnoll RA, George TP, Tyndale RF, Hawk LW Jr. Daily Cigarette Abstinence and Smoking Rate With Varenicline: Relationships With Treatment, Craving, and Affect During the First Week of the Quit Attempt. Nicotine Tob Res. 2025 Nov 23;27(12):2328-2332. doi: 10.1093/ntr/ntaf095. | |
| 38369951 | Derived | Chenoweth MJ, Kim YJ, Nollen NL, Hawk LW Jr, Mahoney MC, Lerman C, Knight J, Tyndale RF. Genetic Prediction of Smoking Cessation Medication Side Effects: A Genome-Wide Investigation of Abnormal Dreams on Varenicline. Clin Pharmacol Ther. 2024 Jun;115(6):1277-1281. doi: 10.1002/cpt.3210. Epub 2024 Feb 19. |
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Subjects were randomly assigned to one of three treatment groups in a 1:1:1 ratio: "Placebo"; "Nicotine Patch"; or "Varenicline". Randomization was stratified by nicotine metabolite ratio - slow metabolizers of nicotine vs. normal metabolizers - and study site and blocked in blocks of 12 to maintain balance. Slow metabolizers were over-sampled.
The trial was conducted at four academic medical centers. From 11/16/2010 to 9/16/2013, participants were recruited through advertisements for a free smoking cessation program.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo (Slow Metabolizers) | Slow metabolizers
|
| FG001 | Placebo (Normal Metabolizers) | Normal metabolizers
|
| FG002 | Nicotine Patch (Slow Metabolizers) | Slow metabolizers
|
| FG003 | Nicotine Patch (Normal Metabolizers) | Normal metabolizers
|
| FG004 | Varenicline (Slow Metabolizers) | Slow metabolizers
|
| FG005 | Varenicline (Normal Metabolizers) | Normal metabolizers
|
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The number of subjects who began treatment period in the project (intention-to-treat).
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo (Slow Metabolizers) | Slow metabolizers
|
| BG001 | Placebo (Normal Metabolizers) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 7-day Point Prevalence Quit Rate at End-of-Treatment (EOT) | The percentage of ITT subjects who were verified as abstinent. Abstinence was defined as no self-reported smoking (not even a puff) for at least 7 days before the telephone assessment, with in-person verification for those self-reporting abstinence. In-person verification consisted of breath carbon monoxide analysis, with a reading of 8 parts-per-million or less confirming abstinence. Subjects who were lost to follow-up were considered smokers. | Intent-to-treat population (all subjects who received at least one dose of intervention). | Posted | Number | percentage of ITT subjects | Week 11 |
|
Adverse event data were collected throughout the entire span of each subject's participation, which is approximately 1 year, 1 month (from initial phone screening to the 12-month follow up survey).
Systematic Assessment: subjects completed a side effect checklist (SEC) during each study session over the course of the treatment period (target quit date through end-of-treatment). The SEC listed anticipated side effects that could be caused by the study medication. Subjects could also spontaneously report AEs at any time.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo (Slow Metabolizers) | Slow metabolizers
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | Systematic Assessment | Episode of atrial fibrillation that required hospitalization |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chest Pain | Cardiac disorders | Systematic Assessment |
A limitation is that few Hispanics or Asians were included.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Paul M. Sanborn, M.S. | University of Pennsylvania | 215-746-7150 | sanborn@mail.med.upenn.edu |
Not provided
| ID | Term |
|---|---|
| D014029 | Tobacco Use Disorder |
| D012907 | Smoking |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
| D001519 | Behavior |
Not provided
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| ID | Term |
|---|---|
| D000068580 | Varenicline |
| D061485 | Tobacco Use Cessation Devices |
| D009538 | Nicotine |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
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|
| Placebo (Normal Metabolizers) | Placebo Comparator | Subjects in this arm are those identified as normal metabolizers of nicotine (based on their NMR) and will take placebo pills daily for twelve weeks & wear a placebo patch daily for eleven weeks. The placebo pill will look identical to the active varenicline tablets; however, they will not contain any active medication. Subjects will follow the same drug regimen as those in the active varenicline arm. The placebo patch will look identical to the active transdermal nicotine patches; however, they do not contain actual nicotine. Subjects will follow the same regimen as those in the active transdermal nicotine arm. All subjects in this arm will receive smoking cessation counseling during their sessions. |
|
| Varenicline (Normal Metabolizers) | Active Comparator | Subjects in this arm are those identified as normal metabolizers of nicotine (based on their NMR) and will take active varenicline pills daily for twelve weeks & wear a placebo patch daily for eleven weeks. When taking the active varenicline, subjects will follow the same treatment regimen per the manufacturer. The placebo patch will look identical to the active transdermal nicotine patches; however, they do not contain actual nicotine. Subjects will follow the same regimen as those in the active transdermal nicotine arm. All subjects in this arm will receive smoking cessation counseling during their sessions. |
|
| Transdermal Nicotine (Normal Metabolizers) | Active Comparator | Subjects in this arm are those identified as normal metabolizers of nicotine (based on their NMR) and will take placebo pills daily for twelve weeks & will wear an active transdermal nicotine patch daily for eleven weeks. The placebo pill will look identical to the active varenicline tablets; however, they will not contain any active medication. Subjects will follow the same drug regimen as those in the active varenicline arm. When wearing the active transdermal nicotine, subjects will follow the same treatment regimen per the manufacturer. All subjects in this arm will receive smoking cessation counseling during their sessions. |
|
|
| Placebo | Drug | Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Week 1 - 6: 21mg placebo patch Week 7 - 8: 14mg placebo patch Week 9 - 11: 7mg placebo patch |
|
|
| Transdermal Nicotine | Drug | Week 1-6: 21mg nicotine patch Week 7-8: 14mg nicotine patch Week 9-11: 7mg nicotine patch |
|
|
| Week 24 |
| Total Side-Effect Severity Index at Pre-Quit | The mean side-effect severity score by treatment group (placebo vs. nicotine patch vs. varenicline) and by NMR group (slow metabolizers vs. normal metabolizers). Side-effect severity was calculated using a Side Effects Checklists (SEC). 29 common side-effects associated with transdermal nicotine or varenicline treatment were rated by participants on a 0 (none) to 3 (severe) scale. For each participant at this timepoint, these scores were summed to calculate a total score, with a range of 0 to 87; a higher score indicated a higher severity of side-effects. | Pre-Quit (Week -1/Baseline) |
| Total Side-Effect Severity Index at Target Quit Date | The mean side-effect severity score by treatment group (placebo vs. nicotine patch vs. varenicline) and by NMR group (slow metabolizers vs. normal metabolizers). Side-effect severity was calculated using a Side Effects Checklists (SEC). 29 common side-effects associated with transdermal nicotine or varenicline treatment were rated by participants on a 0 (none) to 3 (severe) scale. For each participant at this timepoint, these scores were summed to calculate a total score, with a range of 0 to 87; a higher score indicated a higher severity of side-effects. | Target Quit Date (Week 0) |
| Total Side-Effect Severity Index at Week 1 | The mean side-effect severity score by treatment group (placebo vs. nicotine patch vs. varenicline) and by NMR group (slow metabolizers vs. normal metabolizers). Side-effect severity was calculated using a Side Effects Checklists (SEC). 29 common side-effects associated with transdermal nicotine or varenicline treatment were rated by participants on a 0 (none) to 3 (severe) scale. For each participant at this timepoint, these scores were summed to calculate a total score, with a range of 0 to 87; a higher score indicated a higher severity of side-effects. | Week 1 |
| Total Side-Effect Severity Index at Week 4 | The mean side-effect severity score by treatment group (placebo vs. nicotine patch vs. varenicline) and by NMR group (slow metabolizers vs. normal metabolizers). Side-effect severity was calculated using a Side Effects Checklists (SEC). 29 common side-effects associated with transdermal nicotine or varenicline treatment were rated by participants on a 0 (none) to 3 (severe) scale. For each participant at this timepoint, these scores were summed to calculate a total score, with a range of 0 to 87; a higher score indicated a higher severity of side-effects. | Week 4 |
| Philadelphia |
| Pennsylvania |
| 19104 |
| United States |
| MD Anderson Cancer Center, University of Texas | Houston | Texas | 77230 | United States |
| Centre for Addiction and Mental Health, University of Toronto | Toronto | Ontario | M5T1RH | Canada |
| 36789481 | Derived | Chenoweth MJ, Lerman C, Knight J, Tyndale RF. Influence of CYP2A6 Genetic Variation, Nicotine Dependence Severity, and Treatment on Smoking Cessation Success. Nicotine Tob Res. 2023 May 22;25(6):1207-1211. doi: 10.1093/ntr/ntac268. |
| 35639828 | Derived | Tonkin SS, Colder C, Mahoney MC, Swan GE, Cinciripini P, Schnoll R, George TP, Tyndale RF, Hawk LW. Evaluating Treatment Mechanisms of Varenicline: Mediation by Affect and Craving. Nicotine Tob Res. 2022 Oct 26;24(11):1803-1810. doi: 10.1093/ntr/ntac138. |
| 33713409 | Derived | Chenoweth MJ, Lerman C, Knight J, Tyndale RF. A Genome-Wide Association Study of Nausea Incidence in Varenicline-Treated Cigarette Smokers. Nicotine Tob Res. 2021 Aug 29;23(10):1805-1809. doi: 10.1093/ntr/ntab044. |
| 33300144 | Derived | El-Boraie A, Chenoweth MJ, Pouget JG, Benowitz NL, Fukunaga K, Mushiroda T, Kubo M, Nollen NL, Sanderson Cox L, Lerman C, Knight J, Tyndale RF. Transferability of Ancestry-Specific and Cross-Ancestry CYP2A6 Activity Genetic Risk Scores in African and European Populations. Clin Pharmacol Ther. 2021 Oct;110(4):975-985. doi: 10.1002/cpt.2135. Epub 2021 Jan 1. |
| 31502736 | Derived | Peng AR, Swardfager W, Benowitz NL, Ahluwalia JS, Lerman C, Nollen NL, Tyndale RF. Impact of early nausea on varenicline adherence and smoking cessation. Addiction. 2020 Jan;115(1):134-144. doi: 10.1111/add.14810. Epub 2019 Nov 5. |
| 30946162 | Derived | Ashare RL, Thompson M, Leone F, Metzger D, Gross R, Mounzer K, Tyndale RF, Lerman C, Mahoney MC, Cinciripini P, George TP, Collman RG, Schnoll R. Differences in the rate of nicotine metabolism among smokers with and without HIV. AIDS. 2019 May 1;33(6):1083-1088. doi: 10.1097/QAD.0000000000002127. |
| 30614717 | Derived | Robinson JD, Li L, Chen M, Lerman C, Tyndale RF, Schnoll RA, Hawk LW, George TP, Benowitz NL, Cinciripini PM. Evaluating the temporal relationships between withdrawal symptoms and smoking relapse. Psychol Addict Behav. 2019 Mar;33(2):105-116. doi: 10.1037/adb0000434. Epub 2019 Jan 7. |
| 29986268 | Derived | Peng AR, Schnoll R, Hawk LW Jr, Cinciripini P, George TP, Lerman C, Tyndale RF. Predicting smoking abstinence with biological and self-report measures of adherence to varenicline: Impact on pharmacogenetic trial outcomes. Drug Alcohol Depend. 2018 Sep 1;190:72-81. doi: 10.1016/j.drugalcdep.2018.04.035. Epub 2018 Jun 26. |
| 25732567 | Derived | Hamilton DA, Mahoney MC, Novalen M, Chenoweth MJ, Heitjan DF, Lerman C, Tyndale RF, Hawk LW Jr. Test-Retest Reliability and Stability of the Nicotine Metabolite Ratio Among Treatment-Seeking Smokers. Nicotine Tob Res. 2015 Dec;17(12):1505-9. doi: 10.1093/ntr/ntv031. Epub 2015 Mar 1. |
| 25588294 | Derived | Lerman C, Schnoll RA, Hawk LW Jr, Cinciripini P, George TP, Wileyto EP, Swan GE, Benowitz NL, Heitjan DF, Tyndale RF; PGRN-PNAT Research Group. Use of the nicotine metabolite ratio as a genetically informed biomarker of response to nicotine patch or varenicline for smoking cessation: a randomised, double-blind placebo-controlled trial. Lancet Respir Med. 2015 Feb;3(2):131-138. doi: 10.1016/S2213-2600(14)70294-2. Epub 2015 Jan 12. |
| 25012994 | Derived | Chenoweth MJ, Novalen M, Hawk LW Jr, Schnoll RA, George TP, Cinciripini PM, Lerman C, Tyndale RF. Known and novel sources of variability in the nicotine metabolite ratio in a large sample of treatment-seeking smokers. Cancer Epidemiol Biomarkers Prev. 2014 Sep;23(9):1773-82. doi: 10.1158/1055-9965.EPI-14-0427. Epub 2014 Jul 10. |
Normal metabolizers
|
| BG002 | Nicotine Patch (Slow Metabolizers) | Slow metabolizers
|
| BG003 | Nicotine Patch (Normal Metabolizers) | Normal metabolizers
|
| BG004 | Varenicline (Slow Metabolizers) | Slow metabolizers
|
| BG005 | Varenicline (Normal Metabolizers) | Normal metabolizers
|
| BG006 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Education level | Question on Demographics measure (self-report) completed at the Intake session ("What is the highest level of education you completed?"). | Number | participants |
|
| Annual Income (US dollars) | Question on Demographics measure (self-report) completed at the Intake session ("What was your household income before taxes last year?"). | Number | participants |
|
| Employment Status | Question on Demographics measure (self-report) completed at the Intake session ("Are you currently employed full-time or part-time for salary or wages?"). | Number | participants |
|
| FTND Score | The Fagerstrom Test for Nicotine Dependence (FTND) is a six-item self-report scale that measures the level of nicotine dependence. Summary scores are calculated, ranging from 0 to 10, with higher scores indicating a greater difficulty quitting smoking. | Mean | Standard Deviation | units on a scale |
|
| Cigarettes per day | Self-report measure of the number of cigarettes smoked in a typical day. | Mean | Standard Deviation | cigarettes per day |
|
| OG001 | Placebo (Normal Metabolizers) | Normal metabolizers
|
| OG002 | Nicotine Patch (Slow Metabolizers) | Slow metabolizers
|
| OG003 | Nicotine Patch (Normal Metabolizers) | Normal metabolizers
|
| OG004 | Varenicline (Slow Metabolizers) | Slow metabolizers
|
| OG005 | Varenicline (Normal Metabolizers) | Normal metabolizers
|
|
|
| Secondary | 7-day Point Prevalence Quit Rate at 6-month Follow up Survey | The percentage of ITT subjects who were verified as abstinent at the 6-month follow up survey. Abstinence was defined as no self-reported smoking (not even a puff) for at least 7 days before the telephone assessment, with in-person verification for those self-reporting abstinence. In-person verification consisted of breath carbon monoxide analysis, with a reading of 8 parts-per-million or less confirming abstinence. Subjects who were lost to follow-up were considered smokers. | Intent-to-treat population (all subjects who received at least one dose of intervention). | Posted | Number | percentage of ITT subjects | Week 24 |
|
|
|
| Secondary | Total Side-Effect Severity Index at Pre-Quit | The mean side-effect severity score by treatment group (placebo vs. nicotine patch vs. varenicline) and by NMR group (slow metabolizers vs. normal metabolizers). Side-effect severity was calculated using a Side Effects Checklists (SEC). 29 common side-effects associated with transdermal nicotine or varenicline treatment were rated by participants on a 0 (none) to 3 (severe) scale. For each participant at this timepoint, these scores were summed to calculate a total score, with a range of 0 to 87; a higher score indicated a higher severity of side-effects. | Intent-to-treat population (all subjects who received at least one dose of intervention). | Posted | Mean | Standard Deviation | units on a scale | Pre-Quit (Week -1/Baseline) |
|
|
|
| Secondary | Total Side-Effect Severity Index at Target Quit Date | The mean side-effect severity score by treatment group (placebo vs. nicotine patch vs. varenicline) and by NMR group (slow metabolizers vs. normal metabolizers). Side-effect severity was calculated using a Side Effects Checklists (SEC). 29 common side-effects associated with transdermal nicotine or varenicline treatment were rated by participants on a 0 (none) to 3 (severe) scale. For each participant at this timepoint, these scores were summed to calculate a total score, with a range of 0 to 87; a higher score indicated a higher severity of side-effects. | Intent-to-treat population (all subjects who received at least one dose of intervention). | Posted | Mean | Standard Deviation | units on a scale | Target Quit Date (Week 0) |
|
|
|
| Secondary | Total Side-Effect Severity Index at Week 1 | The mean side-effect severity score by treatment group (placebo vs. nicotine patch vs. varenicline) and by NMR group (slow metabolizers vs. normal metabolizers). Side-effect severity was calculated using a Side Effects Checklists (SEC). 29 common side-effects associated with transdermal nicotine or varenicline treatment were rated by participants on a 0 (none) to 3 (severe) scale. For each participant at this timepoint, these scores were summed to calculate a total score, with a range of 0 to 87; a higher score indicated a higher severity of side-effects. | Intent-to-treat population (all subjects who received at least one dose of intervention). | Posted | Mean | Standard Deviation | units on a scale | Week 1 |
|
|
|
| Secondary | Total Side-Effect Severity Index at Week 4 | The mean side-effect severity score by treatment group (placebo vs. nicotine patch vs. varenicline) and by NMR group (slow metabolizers vs. normal metabolizers). Side-effect severity was calculated using a Side Effects Checklists (SEC). 29 common side-effects associated with transdermal nicotine or varenicline treatment were rated by participants on a 0 (none) to 3 (severe) scale. For each participant at this timepoint, these scores were summed to calculate a total score, with a range of 0 to 87; a higher score indicated a higher severity of side-effects. | Intent-to-treat population (all subjects who received at least one dose of intervention). | Posted | Mean | Standard Deviation | units on a scale | Week 4 |
|
|
|
| 10 |
| 215 |
| 194 |
| 215 |
| EG001 | Placebo (Normal Metabolizers) | Normal metabolizers
| 6 | 193 | 171 | 193 |
| EG002 | Nicotine Patch (Slow Metabolizers) | Slow metabolizers
| 11 | 227 | 206 | 227 |
| EG003 | Nicotine Patch (Normal Metabolizers) | Normal metabolizers
| 11 | 191 | 169 | 191 |
| EG004 | Varenicline (Slow Metabolizers) | Slow metabolizers
| 3 | 220 | 210 | 220 |
| EG005 | Varenicline (Normal Metabolizers) | Normal metabolizers
| 8 | 200 | 185 | 200 |
|
| Heart Attack | Cardiac disorders | Systematic Assessment | Episodes of heart attack or heart attack-like symptoms |
|
| Diabetes diagnosis | Endocrine disorders | Systematic Assessment | Diagnosis made during hospitalization following heart attack-like symptoms |
|
| Pancreatitis | Gastrointestinal disorders | Systematic Assessment |
|
| Severe nausea/vomiting/abdominal pain | Gastrointestinal disorders | Systematic Assessment | Symptoms severe enough to require hospitalization. |
|
| Tongue Swelling | Gastrointestinal disorders | Systematic Assessment | Hospitalization due to swelling of the tongue |
|
| Death | General disorders | Systematic Assessment |
|
| Gall bladder issues | Hepatobiliary disorders | Systematic Assessment | Hospitalized due to surgery or issues of the gall bladder |
|
| Pneumonia | Infections and infestations | Systematic Assessment | Hospitalization due to pneumonia |
|
| Ankle injury | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Broken bones | Musculoskeletal and connective tissue disorders | Systematic Assessment | Broken bones due to accidents |
|
| Knee injuries | Musculoskeletal and connective tissue disorders | Systematic Assessment | Knee injuries; may require surgery |
|
| Cancer; colon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment | Diagnosis of colon cancer |
|
| Cancer; lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment | Diagnosis of lung cancer |
|
| Cancer; oral | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment | Diagnosis of oral cancer |
|
| Cancer; throat | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment | Diagnosis of throat cancer |
|
| Moderate cervical dysplasia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment | Unknown whether benign or malignant |
|
| Seizures; cause unknown | Nervous system disorders | Systematic Assessment |
|
| Mood changes | Psychiatric disorders | Systematic Assessment |
|
| Panic Attacks | Psychiatric disorders | Systematic Assessment |
|
| Sleep problems | Psychiatric disorders | Systematic Assessment |
|
| Suicidal thoughts | Psychiatric disorders | Systematic Assessment |
|
| Kidney stone procedure | Renal and urinary disorders | Systematic Assessment |
|
| COPD diagnosis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Hospitalization; COPD diagnosis |
|
| Severe asthma attack | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Required hospitalization |
|
| Abscess drainage; surgery | Surgical and medical procedures | Systematic Assessment |
|
| Skin/bone biopsy | Surgical and medical procedures | Systematic Assessment |
|
| Brain aneurysm | Vascular disorders | Systematic Assessment |
|
| Pulmonary embolism | Vascular disorders | Systematic Assessment |
|
| Stroke | Vascular disorders | Systematic Assessment |
|
| Heart Palpitations | Cardiac disorders | Systematic Assessment |
|
| Irregular Heartbeat | Cardiac disorders | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | Systematic Assessment |
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| Gas | Gastrointestinal disorders | Systematic Assessment |
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| Indigestion | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Dizziness | General disorders | Systematic Assessment |
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| Dry Mouth | General disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Headache | General disorders | Systematic Assessment |
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| Body Weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Feel Weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Abnormal Dreams | Psychiatric disorders | Systematic Assessment |
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| Agitation | Psychiatric disorders | Systematic Assessment |
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| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Depressed Mood | Psychiatric disorders | Systematic Assessment |
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| Disturbed Attention | Psychiatric disorders | Systematic Assessment |
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| Hostility | Psychiatric disorders | Systematic Assessment |
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| Insomnia | Psychiatric disorders | Systematic Assessment |
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| Irritability | Psychiatric disorders | Systematic Assessment |
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| Sleep Problems | Psychiatric disorders | Systematic Assessment |
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| Suicidal Thoughts | Psychiatric disorders | Systematic Assessment |
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| Skin Redness | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Skin Swelling/Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
Not provided
Not provided
| D011810 | Quinoxalines |
| D013812 | Therapeutics |
| D012991 | Solanaceous Alkaloids |
| D000470 | Alkaloids |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |