Smoking, Smoking Cessation
Conditions
Keywords
Nicotine, Nicotine craving
Brief summary
This study is designed to evaluate the ability of a nicotine lozenge to relieve craving for a cigarette compared to a matched placebo (a placebo is like sugar pill and contains no active).
Interventions
DRUGNicotine lower dose
lower dose nicotine lozenge
DRUGNicotine higher dose
higher dose nicotine lozenge
DRUGPlacebo
placebo
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Generally healthy smokers who smoke more than 5 cigarettes per day * Body mass index (BMI) within the range 19-35 kilogram (kg)/meter (m)\^2 * Females of childbearing potential who are, in the opinion of the investigator, practicing a reliable method of contraception.
Exclusion criteria
* Women who are pregnant or who have a positive urine pregnancy test. * Participants with known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. * Clinical Study/Experimental Medication: Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit. * Prior Concomitant Medication: Treatment with enzyme altering agents (e.g. carbamazepine, phenytoin, cimetidine, sodium valporate) within 30 days of the craving provocation visit; Use of any prescription psychoactive medication (such as but not limited to antidepressants, antipsychotics, anxiolytics) within 14 days of the craving provocation visit; Participant has used an over-the-counter (OTC) medication such as antihistamines, sedating agents, or any compound that would have a sedating effect within 24 hours of the craving provocation visit; Current use of any nicotine replacement therapy. * Substance abuse: Recent history or current history (within the last 1 year) of alcohol or other substance abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Nicotine Cravings VAS Scores in Light Smokers | Baseline, 1, 3, 5, 10 and 15 minutes post-treatment | Participants completed a nicotine craving assessment consisting of following five items: I have a desire for a cigarette right now, if it were possible I would smoke right now, All I want right now is a cigarette, I have an urge for a cigarette, I crave a cigarette right now. All participants indicated their craving intensity on a pre-drawn 100 mm scale ranging from 0 (disagree) to 100 (agree). At the end of the craving assessment period, mean VAS score (in mm) was measured. |
| Mean Change From Baseline in Nicotine Cravings VAS Scores in Heavy Smokers | Baseline, 3 minutes and 15 minutes post-treatment | Participants completed a nicotine craving assessment consisting of following five items: I have a desire for a cigarette right now, if it were possible I would smoke right now, All I want right now is a cigarette, I have an urge for a cigarette, I crave a cigarette right now. All participants indicated their craving intensity on a pre-drawn 100 mm scale ranging from 0 (disagree) to 100 (agree). At the end of the craving assessment period, mean VAS score (in mm) was measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders With Improved Craving Scores in Heavy and Light Smokers Group | Baseline prior to provoked craving paradigm, baseline post provoked craving paradigm | Responders were defined as participants with an increase of at least one point (on the 100 point VAS scale) from baseline prior to provoked craving paradigm (B1) to baseline post provoked craving paradigm (B2) on the average cravings score. Percentage of these responders was calculated to evaluate the provocation rate. |
| Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Baseline, 0 minute, 60 minutes and 5 days post treatment | AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with study treatment/s. SAE was defined as any untoward medical occurrence that at any dose results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization results in disability/ incapacity; is a congenital anomaly/ birth defect. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the clinical site.
Pre-assignment details
Participants who smoked more than 5 cigarettes per day were included in the study. Participants were stratified to treatments according to their smoking status: heavy smokers: smoking greater than 20 cigarettes per day and light smokers: smoking between 6 - 20 cigarettes per day.
Participants by arm
| Arm | Count |
|---|---|
| Nicotine Lozenge 4 mg (Heavy Smokers Group) Participants smoking more than 20 cigarettes per day, received a single dose of 4mg nicotine lozenge, through oral route. | 52 |
| Placebo Lozenge 1 (Heavy Smokers Group) Participants smoking more than 20 cigarettes per day, received a single dose of placebo lozenge, through oral route. | 34 |
| Nicotine Lozenge 1.5mg (Light Smokers Group) Participants smoking between 6-20 cigarettes per day, received a single dose of 1.5mg nicotine lozenge, through oral route. | 60 |
| Placebo Lozenge 2 (Light Smokers Group) Participants smoking between 6-20 cigarettes per day, received a single dose of placebo lozenge, through oral route. | 41 |
| Total | 187 |
Baseline characteristics
| Characteristic | Nicotine Lozenge 4 mg (Heavy Smokers Group) | Placebo Lozenge 1 (Heavy Smokers Group) | Nicotine Lozenge 1.5mg (Light Smokers Group) | Placebo Lozenge 2 (Light Smokers Group) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 45.1 Years STANDARD_DEVIATION 10.42 | 45.9 Years STANDARD_DEVIATION 9.43 | 43.9 Years STANDARD_DEVIATION 11.48 | 45.0 Years STANDARD_DEVIATION 10.59 | 45.0 Years STANDARD_DEVIATION 10.48 |
| Nicotine cravings assessment baseline scores on a Visual Analogue scale (VAS) Baseline score post provoked craving paradigm (B2) | 76.03 Score on a scale STANDARD_DEVIATION 24.849 | 78.39 Score on a scale STANDARD_DEVIATION 23.659 | 76.96 Score on a scale STANDARD_DEVIATION 21.667 | 69.1 Score on a scale STANDARD_DEVIATION 26.335 | 75.1 Score on a scale STANDARD_DEVIATION 24.127 |
| Nicotine cravings assessment baseline scores on a Visual Analogue scale (VAS) Baseline score prior provoked craving paradigm(B1) | 68.3 Score on a scale STANDARD_DEVIATION 29.147 | 69.54 Score on a scale STANDARD_DEVIATION 26.534 | 70.00 Score on a scale STANDARD_DEVIATION 20.895 | 62.3 Score on a scale STANDARD_DEVIATION 25.785 | 67.5 Score on a scale STANDARD_DEVIATION 26.09 |
| Sex: Female, Male Female | 23 Participants | 16 Participants | 24 Participants | 21 Participants | 84 Participants |
| Sex: Female, Male Male | 29 Participants | 18 Participants | 36 Participants | 20 Participants | 103 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 60 | 11 / 52 | 0 / 34 | 1 / 41 |
| serious Total, serious adverse events | 0 / 60 | 0 / 52 | 0 / 34 | 0 / 41 |
Outcome results
Primary
Mean Change From Baseline in Nicotine Cravings VAS Scores in Heavy Smokers
Participants completed a nicotine craving assessment consisting of following five items: I have a desire for a cigarette right now, if it were possible I would smoke right now, All I want right now is a cigarette, I have an urge for a cigarette, I crave a cigarette right now. All participants indicated their craving intensity on a pre-drawn 100 mm scale ranging from 0 (disagree) to 100 (agree). At the end of the craving assessment period, mean VAS score (in mm) was measured.
Time frame: Baseline, 3 minutes and 15 minutes post-treatment
Population: ITT population: All randomized participants who had at least one cravings assessment measurement post dose.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotine Lozenge 1.5mg (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Heavy Smokers | 1 minute | -16.82 Score on a scale | Standard Error 2.613 |
| Nicotine Lozenge 1.5mg (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Heavy Smokers | 3 minutes | -29.52 Score on a scale | Standard Error 3.124 |
| Placebo Lozenge 2 (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Heavy Smokers | 1 minute | -13.24 Score on a scale | Standard Error 3.232 |
| Placebo Lozenge 2 (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Heavy Smokers | 3 minutes | -19.82 Score on a scale | Standard Error 3.865 |
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to provoked nicotine cravings, at 1 minute post dosing.p-value: 0.392295% CI: [-11.85, 4.7]ANCOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to provoked nicotine cravings, 3 minutes post dosing.p-value: 0.054795% CI: [-19.59, 0.2]ANCOVA
Primary
Mean Change From Baseline in Nicotine Cravings VAS Scores in Light Smokers
Participants completed a nicotine craving assessment consisting of following five items: I have a desire for a cigarette right now, if it were possible I would smoke right now, All I want right now is a cigarette, I have an urge for a cigarette, I crave a cigarette right now. All participants indicated their craving intensity on a pre-drawn 100 mm scale ranging from 0 (disagree) to 100 (agree). At the end of the craving assessment period, mean VAS score (in mm) was measured.
Time frame: Baseline, 1, 3, 5, 10 and 15 minutes post-treatment
Population: Intent to treat (ITT) population: All randomized participants with at least one cravings assessment measurement post dose were analyzed. No data was imputed in case of dropouts or missing data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotine Lozenge 1.5mg (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Light Smokers | 15 minutes | -38.99 Score on a scale | Standard Error 3.689 |
| Nicotine Lozenge 1.5mg (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Light Smokers | 10 minutes | -35.33 Score on a scale | Standard Error 3.428 |
| Nicotine Lozenge 1.5mg (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Light Smokers | 1 minute | -15.40 Score on a scale | Standard Error 2.439 |
| Nicotine Lozenge 1.5mg (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Light Smokers | 5 minutes | -30.19 Score on a scale | Standard Error 3.257 |
| Nicotine Lozenge 1.5mg (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Light Smokers | 3 minutes | -24.42 Score on a scale | Standard Error 3.108 |
| Placebo Lozenge 2 (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Light Smokers | 5 minutes | -23.86 Score on a scale | Standard Error 3.95 |
| Placebo Lozenge 2 (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Light Smokers | 3 minutes | -17.26 Score on a scale | Standard Error 3.77 |
| Placebo Lozenge 2 (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Light Smokers | 10 minutes | -30.23 Score on a scale | Standard Error 4.158 |
| Placebo Lozenge 2 (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Light Smokers | 15 minutes | -33.99 Score on a scale | Standard Error 4.475 |
| Placebo Lozenge 2 (Light Smokers Group) | Mean Change From Baseline in Nicotine Cravings VAS Scores in Light Smokers | 1 minute | -8.17 Score on a scale | Standard Error 2.958 |
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to provoked nicotine cravings at 1 minute post dosing.p-value: 0.064395% CI: [-14.89, 0.44]ANCOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to provoked nicotine cravings at 3 minute post dosing.p-value: 0.148995% CI: [-16.93, 2.61]ANCOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to provoked nicotine cravings at 5 minute post dosing.p-value: 0.222595% CI: [-16.56, 3.9]ANCOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to provoked nicotine cravings, 10 minutes post dosing.p-value: 0.349195% CI: [-15.87, 5.66]ANCOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to provoked nicotine cravings, 15 minutes post dosing.p-value: 0.393695% CI: [-16.6, 6.59]ANCOVA
Secondary
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with study treatment/s. SAE was defined as any untoward medical occurrence that at any dose results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization results in disability/ incapacity; is a congenital anomaly/ birth defect.
Time frame: Baseline, 0 minute, 60 minutes and 5 days post treatment
Population: Safety population: All randomized participants who received the study treatments were considered evaluable for safety.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nicotine Lozenge 1.5mg (Light Smokers Group) | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AEs | 11 participants |
| Nicotine Lozenge 1.5mg (Light Smokers Group) | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | SAE | 0 participants |
| Placebo Lozenge 2 (Light Smokers Group) | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | SAE | 0 participants |
| Placebo Lozenge 2 (Light Smokers Group) | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AEs | 0 participants |
| Nicotine Lozenge 1.5mg (Light Smokers Group) | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AEs | 1 participants |
| Nicotine Lozenge 1.5mg (Light Smokers Group) | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | SAE | 0 participants |
| Placebo Lozenge 2 (Light Smokers Group) | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AEs | 1 participants |
| Placebo Lozenge 2 (Light Smokers Group) | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | SAE | 0 participants |
Secondary
Percentage of Responders With Improved Craving Scores in Heavy and Light Smokers Group
Responders were defined as participants with an increase of at least one point (on the 100 point VAS scale) from baseline prior to provoked craving paradigm (B1) to baseline post provoked craving paradigm (B2) on the average cravings score. Percentage of these responders was calculated to evaluate the provocation rate.
Time frame: Baseline prior to provoked craving paradigm, baseline post provoked craving paradigm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Lozenge 1.5mg (Light Smokers Group) | Percentage of Responders With Improved Craving Scores in Heavy and Light Smokers Group | 77.2 percentage |
| Placebo Lozenge 2 (Light Smokers Group) | Percentage of Responders With Improved Craving Scores in Heavy and Light Smokers Group | 75.6 percentage |