Smoking
Conditions
Keywords
smoking cessation, nicotine lozenge, nicotine replacement therapy
Brief summary
A multi-center, randomized, double-blind, placebo-controlled, 4-arm clinical study to evaluate efficacy and safety of nicotine lozenge (2mg and 4mg) in smoking cessation in adult cigarette smokers who are motivated to quit smoking. Successful quitters or participants who smoke occasionally will be followed up after week 24 till 12 months.
Interventions
DRUGNicotine
2 mg or 4 mg nicotine lozenge
DRUGPlacebo
placebo lozenge
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
* Participant must be 18 years of age or older; * Participant is motivated in smoking cessation using nicotine mint lozenge; * Participant has the habit of smoking regularly every day for at least 1 year; * Participant is able to read and provide written informed consent.
Exclusion criteria
* Participant uses other forms of tobacco other than cigarettes such as pipes, cigars, snuff, or smokeless tobacco within 30 days of entry into the study; * Participant uses other nicotine delivery system such as nicotine gum, nicotine patch, nicotine inhaler, or nicotine nasal spray etc. within 30 days of study entry; * Participant smoke any other substance within 30 days of study entry (such as cannabis, cocaine, heroin, ice drug, herbal cigarettes etc); * The participant has a past history of alcohol or drug abuse; * Participants use other smoking cessation aids (including bupropion, varenicline, traditional Chinese medicines such as herbals, acupuncture, consultation etc), within 30 days of study entry.; * Participant is currently involved in another clinical trial or has used any investigational medication within 30 days of study entry; Any previous participation in this study; * Participant is a member of the same household as another clinical subject. Subject is a relative of study site staff or member of the study staff; * Participant is pregnant or breast-feeding, or has childbearing potential but refusing taking medical contraception measures (within first 24 weeks during study). (Note: All female subjects with childbearing potential must take urine pregnancy test before entry the study, only negative result subject is permitted to this study.); * Participants who have heart and cerebral vascular disease not stable or controlled by medication or have an irregular heartbeat or have had a heart attack within the last 3 months; * Participants with poorly controlled high blood pressure by medications, systolic BP greater than or equal to 140mmHg, diastolic BP greater than or equal to 90mmHg after administration; * Participants having hyperthyroidism or current application of insulin for diabetes; * Participants having myocardial infarction or cerebral vascular accidents recently (within the past 3 months); * Participants who are unable to fulfill study requirements in relation to conforming to the visit schedule; * Participants who are allergy to Aspartame or Phenylpyruvic acid (an edulcorant is widely used in foods and drinks)，or have diagnosed with Phenylketonuria; * The other clinically significant pulmonary, gastrointestinal, liver, neurological, renal or haematological abnormalities.( unstable or worsening angina pectoris, Prinzmetal's angina, nerve or circulatory problems, rheumatoid arthritis, moderate and severe COPD); * A medical history that, in the opinion of the investigator, might jeopardize the safety of the subject or the validity for the study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Successful Smoking Cessation at Week 6 | From baseline to Week 6 | Rate of Successful Smoking Cessation at Week 6 was measured by Carbon Monoxide (CO) breath levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Long-term Successful Smoking Cessation at Week 24 | From Week 6 to Week 24 | Rate of long-term successful smoking cessation at Week 24 was defined as the proportion of participants who achieved the primary end-point with no more than six cumulative days of smoking from Week 6 to Week 24. |
| Proportion of Participants With Seven Day Point Prevalence Abstinence | Weekly assessment at Week 1, 2, 4, 6, 12 and Week 24 | Seven day point prevalence abstinence was defined as complete abstinence from smoking for the 7 days up to and including the evaluation day. |
| Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Weekly assessment at Week 1, 2, 3, 4, 5 and Week 6 | The evaluation of withdrawal and craving symptoms was carried out every day with the Minnesota Nicotine Withdrawal scale (MNWS). The MNWS total score contains 9 items (urge to smoke; depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating; restlessness; increased appetite; difficulty going to sleep; difficulty staying asleep). Each item was rated on a 5 grade scale with scores ranging from 0 (best score) to 4 (worst score) i.e. none (score=0), slight (score=1), mild (score=2), moderate (score=3), and severe (score=4). For each symptom at each week, the average score was calculated as the average of the daily scores during that week. The total score was calculated as the sum of the 9 symptoms. |
| Rate of Continuous Successful Smoking Cessation at Week 12 and Week 24 | From baseline to Week 12 and Week 24 | Continuous abstinence was verified by measurement of CO breath levels. |
| Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Baseline, Week 6, 12 and Week 24 | Change in body weight was analyzed at Weeks 6, 12, and 24. |
| Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | Weekly assessments from first treatment dose up to 15 days after last treatment dose | All AEs and SAEs were reviewed and reported by investigator. AEs were graded on a 3-point scale as Mild, Moderate and Severe. |
| Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Weeks 1-2, 3-4, 5-6, 7-12 and 13-24 | Mean daily dose of lozenges was calculated as number of lozenges taken at each visit divided by days since the last visit. |
Participant flow
Recruitment details
Participants were recruited at the clinical site.
Pre-assignment details
Of 781 screened participants, only 723 were randomized and remaining 58 were considered screening failures. Participants who smoked their first cigarette within 30 minutes after waking were considered as high dependence smokers while those who smoked their first cigarette after 30 minutes of waking were considered as low dependence smokers.
Participants by arm
| Arm | Count |
|---|---|
| Nicotine Lozenge 2 mg (Low Dependence Smokers) Participants who smoked their first cigarette after 30 minutes of waking received 2 mg of nicotine lozenge, orally. | 241 |
| Placebo Lozenge (Low Dependence Smokers) Participants who smoked their first cigarette after 30 minutes of waking received placebo lozenge containing 0 mg of nicotine, orally. | 242 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) Participants who smoked their first cigarette within 30 minutes after waking received 4 mg nicotine lozenge, orally. | 120 |
| Placebo Lozenge (High Dependence Smokers) Participants who smoked their first cigarette within 30 minutes after waking received placebo lozenge containing 0 mg of nicotine, orally. | 119 |
| Total | 722 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 | 2 | 2 |
| Overall Study | Lack of Efficacy | 5 | 6 | 1 | 3 |
| Overall Study | Lost to Follow-up | 4 | 11 | 2 | 3 |
| Overall Study | Other Reason | 6 | 1 | 4 | 2 |
| Overall Study | Protocol Violation | 1 | 2 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | Nicotine Lozenge 2 mg (Low Dependence Smokers) | Placebo Lozenge (Low Dependence Smokers) | Nicotine Lozenge 4 mg (High Dependence Smokers) | Placebo Lozenge (High Dependence Smokers) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 38.4 Years STANDARD_DEVIATION 11.78 | 39.9 Years STANDARD_DEVIATION 11.76 | 42.3 Years STANDARD_DEVIATION 10.38 | 42.0 Years STANDARD_DEVIATION 10.57 | 40.1 Years STANDARD_DEVIATION 11.44 |
| Body Weight | 71.8 Kg STANDARD_DEVIATION 11.06 | 72.3 Kg STANDARD_DEVIATION 11.42 | 75.9 Kg STANDARD_DEVIATION 11.64 | 74.3 Kg STANDARD_DEVIATION 12.15 | 73.1 Kg STANDARD_DEVIATION 11.53 |
| Sex: Female, Male Female | 11 Participants | 7 Participants | 2 Participants | 3 Participants | 23 Participants |
| Sex: Female, Male Male | 230 Participants | 235 Participants | 118 Participants | 116 Participants | 699 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 | 59 / 241 | 45 / 242 | 43 / 119 | 26 / 118 |
| serious Total, serious adverse events | 1 / 241 | 0 / 242 | 1 / 119 | 1 / 118 |
Outcome results
Primary
Rate of Successful Smoking Cessation at Week 6
Rate of Successful Smoking Cessation at Week 6 was measured by Carbon Monoxide (CO) breath levels.
Time frame: From baseline to Week 6
Population: Analysis was considered per Full Analysis Set (FAS) population. FAS population consisted of all randomized participants who had study medication for at least once with assessment data post-dosing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Rate of Successful Smoking Cessation at Week 6 | 24.48 Percentage of participants |
| Placebo Lozenge (Low Dependence Smokers) | Rate of Successful Smoking Cessation at Week 6 | 21.49 Percentage of participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Rate of Successful Smoking Cessation at Week 6 | 30.83 Percentage of participants |
| Placebo Lozenge (High Dependence Smokers) | Rate of Successful Smoking Cessation at Week 6 | 20.17 Percentage of participants |
Comparison: Null hypothesis considered no treatment difference in the smoking cessation success rate for the active treatment versus its matching placebo.p-value: 0.385195% CI: [0.78, 1.92]Cochran-Mantel-Haenszel
Comparison: Null hypothesis considered no treatment difference in the smoking cessation success rate for the active treatment versus its matching placebo.p-value: 0.056595% CI: [0.99, 3.32]Cochran-Mantel-Haenszel
Secondary
Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination.
Change in body weight was analyzed at Weeks 6, 12, and 24.
Time frame: Baseline, Week 6, 12 and Week 24
Population: Analysis was carried out per FAS population, which consisted of all randomized subjects who had study medication for at least once with assessment data post-dosing. Due to drop outs, there was difference in the population analyzed (n) for this outcome measure at each time point i.e. Week 6, Week 12 and Week 24. Missing values were not imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Week 6 (n=225, 230, 115, 109) | 0.9 kilogram (kg) | Standard Deviation 1.94 |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Week 24 (n=221, 224, 111, 112) | 1.3 kilogram (kg) | Standard Deviation 2.89 |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Week 12 (n=221, 225, 112, 107) | 1.2 kilogram (kg) | Standard Deviation 2.43 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Week 6 (n=225, 230, 115, 109) | 0.7 kilogram (kg) | Standard Deviation 2.21 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Week 24 (n=221, 224, 111, 112) | 1.3 kilogram (kg) | Standard Deviation 2.81 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Week 12 (n=221, 225, 112, 107) | 1.0 kilogram (kg) | Standard Deviation 2.4 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Week 12 (n=221, 225, 112, 107) | 1.9 kilogram (kg) | Standard Deviation 3.58 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Week 6 (n=225, 230, 115, 109) | 1.2 kilogram (kg) | Standard Deviation 2.45 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Week 24 (n=221, 224, 111, 112) | 2.2 kilogram (kg) | Standard Deviation 3.14 |
| Placebo Lozenge (High Dependence Smokers) | Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Week 6 (n=225, 230, 115, 109) | 1.2 kilogram (kg) | Standard Deviation 2.16 |
| Placebo Lozenge (High Dependence Smokers) | Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Week 24 (n=221, 224, 111, 112) | 2.1 kilogram (kg) | Standard Deviation 2.5 |
| Placebo Lozenge (High Dependence Smokers) | Mean Change From Baseline in Body Weight at Week 6, Week 12 and Week 24/ Premature Termination. | Week 12 (n=221, 225, 112, 107) | 1.5 kilogram (kg) | Standard Deviation 2.17 |
Secondary
Mean Daily Dose at Visit 4, 5, 6, 7 and 10
Mean daily dose of lozenges was calculated as number of lozenges taken at each visit divided by days since the last visit.
Time frame: Weeks 1-2, 3-4, 5-6, 7-12 and 13-24
Population: Analysis was carried out per FAS population, which consisted of all randomized subjects who had study medication for at least once with assessment data post-dosing. Due to drop outs, there was difference in the population analyzed (n) for this outcome measure at each time point. Missing values were not imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Weeks 7-12 (n=221, 224, 112, 106) | 4.85 Number of lozenges | Standard Deviation 2.33 |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Week 3-4 (n=224, 231, 114, 107) | 8.66 Number of lozenges | Standard Deviation 3.17 |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Weeks 13-24 (n=222, 222, 105, 107) | 0.89 Number of lozenges | Standard Deviation 1.05 |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Week 5-6 (n=223, 228, 113, 106) | 8.15 Number of lozenges | Standard Deviation 3.39 |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Week 1-2 (n=232, 237, 117, 111) | 8.96 Number of lozenges | Standard Deviation 3.32 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Week 5-6 (n=223, 228, 113, 106) | 8.07 Number of lozenges | Standard Deviation 3.3 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Weeks 7-12 (n=221, 224, 112, 106) | 4.54 Number of lozenges | Standard Deviation 2.4 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Weeks 13-24 (n=222, 222, 105, 107) | 0.78 Number of lozenges | Standard Deviation 1.04 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Week 3-4 (n=224, 231, 114, 107) | 8.71 Number of lozenges | Standard Deviation 3.4 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Week 1-2 (n=232, 237, 117, 111) | 8.59 Number of lozenges | Standard Deviation 3.23 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Week 5-6 (n=223, 228, 113, 106) | 8.55 Number of lozenges | Standard Deviation 3.32 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Week 1-2 (n=232, 237, 117, 111) | 8.81 Number of lozenges | Standard Deviation 3.57 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Week 3-4 (n=224, 231, 114, 107) | 8.93 Number of lozenges | Standard Deviation 3.17 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Weeks 7-12 (n=221, 224, 112, 106) | 5.02 Number of lozenges | Standard Deviation 2.35 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Weeks 13-24 (n=222, 222, 105, 107) | 0.95 Number of lozenges | Standard Deviation 0.9 |
| Placebo Lozenge (High Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Weeks 7-12 (n=221, 224, 112, 106) | 4.67 Number of lozenges | Standard Deviation 2.31 |
| Placebo Lozenge (High Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Week 3-4 (n=224, 231, 114, 107) | 8.60 Number of lozenges | Standard Deviation 3.39 |
| Placebo Lozenge (High Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Week 1-2 (n=232, 237, 117, 111) | 8.52 Number of lozenges | Standard Deviation 3.16 |
| Placebo Lozenge (High Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Week 5-6 (n=223, 228, 113, 106) | 8.09 Number of lozenges | Standard Deviation 3.43 |
| Placebo Lozenge (High Dependence Smokers) | Mean Daily Dose at Visit 4, 5, 6, 7 and 10 | Weeks 13-24 (n=222, 222, 105, 107) | 0.84 Number of lozenges | Standard Deviation 0.92 |
Secondary
Mean Score of Relief of Craving/ Total Withdrawal Symptoms
The evaluation of withdrawal and craving symptoms was carried out every day with the Minnesota Nicotine Withdrawal scale (MNWS). The MNWS total score contains 9 items (urge to smoke; depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating; restlessness; increased appetite; difficulty going to sleep; difficulty staying asleep). Each item was rated on a 5 grade scale with scores ranging from 0 (best score) to 4 (worst score) i.e. none (score=0), slight (score=1), mild (score=2), moderate (score=3), and severe (score=4). For each symptom at each week, the average score was calculated as the average of the daily scores during that week. The total score was calculated as the sum of the 9 symptoms.
Time frame: Weekly assessment at Week 1, 2, 3, 4, 5 and Week 6
Population: Analysis was carried out per FAS population, which consisted of all randomized subjects who have had study medication for at least once with assessment data post-dosing. Due to drop outs, there was difference in the number of participants analyzed (n) for this outcome measure. Missing values were not imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 2 (n=230, 233, 112, 115) | 7.59 Score on a scale | Standard Deviation 7.25 |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 1 (n=236, 238, 119, 118) | 8.40 Score on a scale | Standard Deviation 7.18 |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 3 (n=226, 232, 115, 110) | 6.80 Score on a scale | Standard Deviation 7.12 |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 4 (n=225, 226, 113, 108) | 6.67 Score on a scale | Standard Deviation 7.36 |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 5 (n=221, 229, 112, 104) | 6.06 Score on a scale | Standard Deviation 6.57 |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 6 (215, 223, 103, 102) | 5.85 Score on a scale | Standard Deviation 6.53 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 6 (215, 223, 103, 102) | 5.45 Score on a scale | Standard Deviation 6.02 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 4 (n=225, 226, 113, 108) | 5.45 Score on a scale | Standard Deviation 5.59 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 1 (n=236, 238, 119, 118) | 7.77 Score on a scale | Standard Deviation 6.55 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 3 (n=226, 232, 115, 110) | 6.06 Score on a scale | Standard Deviation 5.83 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 2 (n=230, 233, 112, 115) | 6.84 Score on a scale | Standard Deviation 6.05 |
| Placebo Lozenge (Low Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 5 (n=221, 229, 112, 104) | 5.29 Score on a scale | Standard Deviation 5.72 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 2 (n=230, 233, 112, 115) | 6.70 Score on a scale | Standard Deviation 5.96 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 3 (n=226, 232, 115, 110) | 6.17 Score on a scale | Standard Deviation 6.4 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 4 (n=225, 226, 113, 108) | 5.66 Score on a scale | Standard Deviation 6.19 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 6 (215, 223, 103, 102) | 5.21 Score on a scale | Standard Deviation 5.58 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 5 (n=221, 229, 112, 104) | 5.60 Score on a scale | Standard Deviation 5.98 |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 1 (n=236, 238, 119, 118) | 7.66 Score on a scale | Standard Deviation 6.08 |
| Placebo Lozenge (High Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 1 (n=236, 238, 119, 118) | 8.67 Score on a scale | Standard Deviation 7.02 |
| Placebo Lozenge (High Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 5 (n=221, 229, 112, 104) | 6.60 Score on a scale | Standard Deviation 5.94 |
| Placebo Lozenge (High Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 6 (215, 223, 103, 102) | 6.49 Score on a scale | Standard Deviation 6.23 |
| Placebo Lozenge (High Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 4 (n=225, 226, 113, 108) | 6.71 Score on a scale | Standard Deviation 6.06 |
| Placebo Lozenge (High Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 2 (n=230, 233, 112, 115) | 7.39 Score on a scale | Standard Deviation 6.12 |
| Placebo Lozenge (High Dependence Smokers) | Mean Score of Relief of Craving/ Total Withdrawal Symptoms | Week 3 (n=226, 232, 115, 110) | 6.90 Score on a scale | Standard Deviation 5.97 |
Secondary
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs
All AEs and SAEs were reviewed and reported by investigator. AEs were graded on a 3-point scale as Mild, Moderate and Severe.
Time frame: Weekly assessments from first treatment dose up to 15 days after last treatment dose
Population: Safety Population of this study consists of all randomized participants who have had study medication for at least once.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | AEs | 111 Participants |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | SAEs | 1 Participants |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | Cardiovascular AEs | 24 Participants |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | Discontinuation due to AEs | 3 Participants |
| Placebo Lozenge (Low Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | SAEs | 0 Participants |
| Placebo Lozenge (Low Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | Cardiovascular AEs | 3 Participants |
| Placebo Lozenge (Low Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | Discontinuation due to AEs | 2 Participants |
| Placebo Lozenge (Low Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | AEs | 91 Participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | Cardiovascular AEs | 11 Participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | SAEs | 1 Participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | Discontinuation due to AEs | 1 Participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | AEs | 61 Participants |
| Placebo Lozenge (High Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | Discontinuation due to AEs | 2 Participants |
| Placebo Lozenge (High Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | SAEs | 1 Participants |
| Placebo Lozenge (High Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | AEs | 58 Participants |
| Placebo Lozenge (High Dependence Smokers) | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Cardiovascular AEs and Who Discontinued Due to AEs | Cardiovascular AEs | 10 Participants |
Secondary
Proportion of Participants With Seven Day Point Prevalence Abstinence
Seven day point prevalence abstinence was defined as complete abstinence from smoking for the 7 days up to and including the evaluation day.
Time frame: Weekly assessment at Week 1, 2, 4, 6, 12 and Week 24
Population: Analysis was carried out per FAS population. FAS population consisted of all randomized subjects who had study medication for at least once with assessment data post-dosing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 12 | 41.49 Percentage of participants |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 2 | 21.16 Percentage of participants |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 24 | 41.49 Percentage of participants |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 4 | 31.95 Percentage of participants |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 6 | 35.68 Percentage of participants |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 1 | 12.45 Percentage of participants |
| Placebo Lozenge (Low Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 4 | 29.34 Percentage of participants |
| Placebo Lozenge (Low Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 1 | 11.98 Percentage of participants |
| Placebo Lozenge (Low Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 12 | 39.26 Percentage of participants |
| Placebo Lozenge (Low Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 6 | 37.19 Percentage of participants |
| Placebo Lozenge (Low Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 24 | 43.80 Percentage of participants |
| Placebo Lozenge (Low Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 2 | 23.14 Percentage of participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 24 | 50.00 Percentage of participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 2 | 33.33 Percentage of participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 6 | 41.67 Percentage of participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 4 | 36.67 Percentage of participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 1 | 20.00 Percentage of participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 12 | 40.83 Percentage of participants |
| Placebo Lozenge (High Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 24 | 43.70 Percentage of participants |
| Placebo Lozenge (High Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 1 | 10.08 Percentage of participants |
| Placebo Lozenge (High Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 2 | 26.05 Percentage of participants |
| Placebo Lozenge (High Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 4 | 30.25 Percentage of participants |
| Placebo Lozenge (High Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 6 | 32.77 Percentage of participants |
| Placebo Lozenge (High Dependence Smokers) | Proportion of Participants With Seven Day Point Prevalence Abstinence | Week 12 | 26.05 Percentage of participants |
Secondary
Rate of Continuous Successful Smoking Cessation at Week 12 and Week 24
Continuous abstinence was verified by measurement of CO breath levels.
Time frame: From baseline to Week 12 and Week 24
Population: Analysis was done per FAS population. FAS population consisted of all randomized subjects who had study medication for at least once with assessment data post-dosing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Rate of Continuous Successful Smoking Cessation at Week 12 and Week 24 | Smoking Cessation Rate at 12 weeks | 17.84 Percentage of participants |
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Rate of Continuous Successful Smoking Cessation at Week 12 and Week 24 | Smoking Cessation Rate at 24 weeks | 12.86 Percentage of participants |
| Placebo Lozenge (Low Dependence Smokers) | Rate of Continuous Successful Smoking Cessation at Week 12 and Week 24 | Smoking Cessation Rate at 24 weeks | 13.22 Percentage of participants |
| Placebo Lozenge (Low Dependence Smokers) | Rate of Continuous Successful Smoking Cessation at Week 12 and Week 24 | Smoking Cessation Rate at 12 weeks | 16.94 Percentage of participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Rate of Continuous Successful Smoking Cessation at Week 12 and Week 24 | Smoking Cessation Rate at 12 weeks | 22.50 Percentage of participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Rate of Continuous Successful Smoking Cessation at Week 12 and Week 24 | Smoking Cessation Rate at 24 weeks | 19.17 Percentage of participants |
| Placebo Lozenge (High Dependence Smokers) | Rate of Continuous Successful Smoking Cessation at Week 12 and Week 24 | Smoking Cessation Rate at 12 weeks | 10.92 Percentage of participants |
| Placebo Lozenge (High Dependence Smokers) | Rate of Continuous Successful Smoking Cessation at Week 12 and Week 24 | Smoking Cessation Rate at 24 weeks | 10.08 Percentage of participants |
Secondary
Rate of Long-term Successful Smoking Cessation at Week 24
Rate of long-term successful smoking cessation at Week 24 was defined as the proportion of participants who achieved the primary end-point with no more than six cumulative days of smoking from Week 6 to Week 24.
Time frame: From Week 6 to Week 24
Population: Analysis was done per FAS population. FAS population consisted of all randomized subjects who had study medication for at least once with assessment data post-dosing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Lozenge 2 mg (Low Dependence Smokers) | Rate of Long-term Successful Smoking Cessation at Week 24 | 19.09 Percentage of participants |
| Placebo Lozenge (Low Dependence Smokers) | Rate of Long-term Successful Smoking Cessation at Week 24 | 17.77 Percentage of participants |
| Nicotine Lozenge 4 mg (High Dependence Smokers) | Rate of Long-term Successful Smoking Cessation at Week 24 | 24.17 Percentage of participants |
| Placebo Lozenge (High Dependence Smokers) | Rate of Long-term Successful Smoking Cessation at Week 24 | 15.97 Percentage of participants |