* The efficacy of Varenicline (the active ingredient of SmokeLESS) in smoking cessation was demonstrated in six clinical trials in which a total of 3659 chronic cigarette smokers (>/= 10 cigarettes per day) were treated with Varenicline.
In all clinical studies, abstinence from smoking was determined by patient self-report and verified by measurement of exhaled carbon monoxide (CO</=10 ppm) at weekly visits.
Among the Varenicline treated patients enrolled in these studies, the completion rate was 65%.
Except for the initial Phase 2 study (Study 1) and the maintenance of abstinence study (Study 6), patients were treated for 12 weeks and then were followed for 40 weeks post-treatment.
Most subjects enrolled in these trials were white (79% - 96%).
All studies enrolled almost equal numbers of men and women.
The average age of subjects in these studies was 43 years.
Subjects on average had smoked about 21 cigarettes per day for an average of approximately 25 years.

* In all studies, patients were provided with an educational booklet on smoking cessation and received up to 10 minutes of smoking cessation counseling at each weekly treatment visit according to Agency for Healthcare Research and Quality guidelines.
Patients set a date to stop smoking (target quit date, TQD) with dosing starting 1 week before this date.

Initiation of Abstinence

* Study 1: This was a six-week dose-ranging study comparing Varenicline to placebo.
This study provided initial evidence that Varenicline at a total dose of 1 mg per day or 2 mg per day was effective as an aid to smoking cessation.

* Study 2: This study of 627 subjects compared Varenicline 1 mg per day and 2 mg per day with placebo.
Patients were treated for 12 weeks (including one week titration) and then were followed for 40 weeks post-treatment.
Varenicline was given in two divided doses.
Each dose of Varenicline was given in two different regimens, with and without initial dose titration, to explore the effect of different dosing regimens on tolerability.
For the titrated groups, dosage was titrated up over the course of one week, with full dosage achieved starting with the second week of dosing.
The titrated and nontitrated groups were pooled for efficacy analysis.

* Forty five percent of subjects receiving Varenicline 1 mg per day (0.5 mg BID) and 51% of subjects receiving 2 mg per day (1 mg BID) had CO-confirmed continuous abstinence during weeks 9 through 12 compared to 12% of subjects in the placebo group.
In addition, 31% of the 1 mg per day group and 31% of the 2 mg per day group were continuously abstinent from one week after TQD through the end of treatment as compared to 8% of the placebo group.

* Study 3: This flexible-dosing study of 312 subjects examined the effect of a patient-directed dosing strategy of Varenicline or placebo.
After an initial one-week titration to a dose of 0.5 mg BID, subjects could adjust their dosage as often as they wished between 0.5 mg QD to 1 mg BID per day.
Sixty nine percent of patients titrated to the maximum allowable dose at any time during the study.
For 44% of patients, the modal dose selected was 1 mg BID; for slightly over half of the study participants, the modal dose selected was 1 mg/day or less.

* Of the subjects treated with Varenicline, 40% had CO-confirmed continuous abstinence during weeks 9 through 12 compared to 12% in the placebo group.
In addition, 29% of the Varenicline group were continuously abstinent from one week after TQD through the end of treatment as compared to 9% of the placebo group.

* Study 4 and Study 5: These identical double-blind studies compared Varenicline 2 mg per day, bupropion sustained release (SR) 150 mg BID, and placebo.
Patients were treated for 12 weeks and then were followed for 40 weeks post-treatment.
The Varenicline dosage of 1 mg BID was achieved using a titration of 0.5 mg QD for the initial 3 days followed by 0.5 mg BID for the next 4 days.
The bupropion SR dosage of 150 mg BID was achieved using a 3-day titration of 150 mg QD.
Study 4 enrolled 1022 subjects and Study 5 enrolled 1023 subjects.
Patients inappropriate for bupropion treatment or patients who had previously used bupropion were excluded.

● In Study 4, subjects treated with Varenicline had a superior rate of CO-confirmed abstinence during weeks 9 through 12 (44%) compared to patients treated with bupropion SR (30%) or placebo (17%).
The bupropion SR quit rate was also superior to placebo.
In addition, 29% of the Varenicline group were continuously abstinent from one week after TQD through the end of treatment as compared to 12% of the placebo group and 23% of the bupropion SR group.

● Similarly in Study 5, subjects treated with Varenicline had a superior rate of CO-confirmed abstinence during weeks 9 through 12 (44%) compared to patients treated with bupropion SR (30%) or placebo (18%).
The bupropion SR quit rate was also superior to placebo.
In addition, 29% of the Varenicline group were continuously abstinent from one week after TQD through the end of treatment as compared to 11% of the placebo group and 21% of the bupropion SR group.

● The efficacy of Varenicline (the active ingredient of SmokeLESS) in smoking cessation was demonstrated in six clinical trials in which a total of 3659 chronic cigarette smokers (>/= 10 cigarettes per day) were treated with Varenicline.
In all clinical studies, abstinence from smoking was determined by patient self-report and verified by measurement of exhaled carbon monoxide (CO</=10 ppm) at weekly visits.
Among the Varenicline treated patients enrolled in these studies, the completion rate was 65%.
Except for the initial Phase 2 study (Study 1) and the maintenance of abstinence study (Study 6), patients were treated for 12 weeks and then were followed for 40 weeks post-treatment.
Most subjects enrolled in these trials were white (79% - 96%).
All studies enrolled almost equal numbers of men and women.
The average age of subjects in these studies was 43 years.
Subjects on average had smoked about 21 cigarettes per day for an average of approximately 25 years.

● In all studies, patients were provided with an educational booklet on smoking cessation and received up to 10 minutes of smoking cessation counseling at each weekly treatment visit according to Agency for Healthcare Research and Quality guidelines.
Patients set a date to stop smoking (target quit date, TQD) with dosing starting 1 week before this date.

Initiation of Abstinence

● Study 1: This was a six-week dose-ranging study comparing Varenicline to placebo.
This study provided initial evidence that Varenicline at a total dose of 1 mg per day or 2 mg per day was effective as an aid to smoking cessation.

● Study 2: This study of 627 subjects compared Varenicline 1 mg per day and 2 mg per day with placebo.
Patients were treated for 12 weeks (including one week titration) and then were followed for 40 weeks post-treatment.
Varenicline was given in two divided doses.
Each dose of Varenicline was given in two different regimens, with and without initial dose titration, to explore the effect of different dosing regimens on tolerability.
For the titrated groups, dosage was titrated up over the course of one week, with full dosage achieved starting with the second week of dosing.
The titrated and nontitrated groups were pooled for efficacy analysis.

● Forty five percent of subjects receiving Varenicline 1 mg per day (0.5 mg BID) and 51% of subjects receiving 2 mg per day (1 mg BID) had CO-confirmed continuous abstinence during weeks 9 through 12 compared to 12% of subjects in the placebo group.
In addition, 31% of the 1 mg per day group and 31% of the 2 mg per day group were continuously abstinent from one week after TQD through the end of treatment as compared to 8% of the placebo group.

● Study 3: This flexible-dosing study of 312 subjects examined the effect of a patient-directed dosing strategy of Varenicline or placebo.
After an initial one-week titration to a dose of 0.5 mg BID, subjects could adjust their dosage as often as they wished between 0.5 mg QD to 1 mg BID per day.
Sixty nine percent of patients titrated to the maximum allowable dose at any time during the study.
For 44% of patients, the modal dose selected was 1 mg BID; for slightly over half of the study participants, the modal dose selected was 1 mg/day or less.

● Of the subjects treated with Varenicline, 40% had CO-confirmed continuous abstinence during weeks 9 through 12 compared to 12% in the placebo group.
In addition, 29% of the Varenicline group were continuously abstinent from one week after TQD through the end of treatment as compared to 9% of the placebo group.

● Study 4 and Study 5: These identical double-blind studies compared Varenicline 2 mg per day, bupropion sustained release (SR) 150 mg BID, and placebo.
Patients were treated for 12 weeks and then were followed for 40 weeks post-treatment.
The Varenicline dosage of 1 mg BID was achieved using a titration of 0.5 mg QD for the initial 3 days followed by 0.5 mg BID for the next 4 days.
The bupropion SR dosage of 150 mg BID was achieved using a 3-day titration of 150 mg QD.
Study 4 enrolled 1022 subjects and Study 5 enrolled 1023 subjects.
Patients inappropriate for bupropion treatment or patients who had previously used bupropion were excluded.

● In Study 4, subjects treated with Varenicline had a superior rate of CO-confirmed abstinence during weeks 9 through 12 (44%) compared to patients treated with bupropion SR (30%) or placebo (17%).
The bupropion SR quit rate was also superior to placebo.
In addition, 29% of the Varenicline group were continuously abstinent from one week after TQD through the end of treatment as compared to 12% of the placebo group and 23% of the bupropion SR group.

● Similarly in Study 5, subjects treated with Varenicline had a superior rate of CO-confirmed abstinence during weeks 9 through 12 (44%) compared to patients treated with bupropion SR (30%) or placebo (18%).
The bupropion SR quit rate was also superior to placebo.
In addition, 29% of the Varenicline group were continuously abstinent from one week after TQD through the end of treatment as compared to 11% of the placebo group and 21% of the bupropion SR group.

● The efficacy of Varenicline (the active ingredient of SmokeLESS) in smoking cessation was demonstrated in six clinical trials in which a total of 3659 chronic cigarette smokers (>/= 10 cigarettes per day) were treated with Varenicline.
In all clinical studies, abstinence from smoking was determined by patient self-report and verified by measurement of exhaled carbon monoxide (CO</=10 ppm) at weekly visits.
Among the Varenicline treated patients enrolled in these studies, the completion rate was 65%.
Except for the initial Phase 2 study (Study 1) and the maintenance of abstinence study (Study 6), patients were treated for 12 weeks and then were followed for 40 weeks post-treatment.
Most subjects enrolled in these trials were white (79% - 96%).
All studies enrolled almost equal numbers of men and women.
The average age of subjects in these studies was 43 years.
Subjects on average had smoked about 21 cigarettes per day for an average of approximately 25 years.

● In all studies, patients were provided with an educational booklet on smoking cessation and received up to 10 minutes of smoking cessation counseling at each weekly treatment visit according to Agency for Healthcare Research and Quality guidelines.
Patients set a date to stop smoking (target quit date, TQD) with dosing starting 1 week before this date.

Initiation of Abstinence

● Study 1: This was a six-week dose-ranging study comparing Varenicline to placebo.
This study provided initial evidence that Varenicline at a total dose of 1 mg per day or 2 mg per day was effective as an aid to smoking cessation.

● Study 2: This study of 627 subjects compared Varenicline 1 mg per day and 2 mg per day with placebo.
Patients were treated for 12 weeks (including one week titration) and then were followed for 40 weeks post-treatment.
Varenicline was given in two divided doses.
Each dose of Varenicline was given in two different regimens, with and without initial dose titration, to explore the effect of different dosing regimens on tolerability.
For the titrated groups, dosage was titrated up over the course of one week, with full dosage achieved starting with the second week of dosing.
The titrated and nontitrated groups were pooled for efficacy analysis.

● Forty five percent of subjects receiving Varenicline 1 mg per day (0.5 mg BID) and 51% of subjects receiving 2 mg per day (1 mg BID) had CO-confirmed continuous abstinence during weeks 9 through 12 compared to 12% of subjects in the placebo group.
In addition, 31% of the 1 mg per day group and 31% of the 2 mg per day group were continuously abstinent from one week after TQD through the end of treatment as compared to 8% of the placebo group.

● Study 3: This flexible-dosing study of 312 subjects examined the effect of a patient-directed dosing strategy of Varenicline or placebo.
After an initial one-week titration to a dose of 0.5 mg BID, subjects could adjust their dosage as often as they wished between 0.5 mg QD to 1 mg BID per day.
Sixty nine percent of patients titrated to the maximum allowable dose at any time during the study.
For 44% of patients, the modal dose selected was 1 mg BID; for slightly over half of the study participants, the modal dose selected was 1 mg/day or less.

● Of the subjects treated with Varenicline, 40% had CO-confirmed continuous abstinence during weeks 9 through 12 compared to 12% in the placebo group.
In addition, 29% of the Varenicline group were continuously abstinent from one week after TQD through the end of treatment as compared to 9% of the placebo group.

● Study 4 and Study 5: These identical double-blind studies compared Varenicline 2 mg per day, bupropion sustained release (SR) 150 mg BID, and placebo.
Patients were treated for 12 weeks and then were followed for 40 weeks post-treatment.
The Varenicline dosage of 1 mg BID was achieved using a titration of 0.5 mg QD for the initial 3 days followed by 0.5 mg BID for the next 4 days.
The bupropion SR dosage of 150 mg BID was achieved using a 3-day titration of 150 mg QD.
Study 4 enrolled 1022 subjects and Study 5 enrolled 1023 subjects.
Patients inappropriate for bupropion treatment or patients who had previously used bupropion were excluded.

● In Study 4, subjects treated with Varenicline had a superior rate of CO-confirmed abstinence during weeks 9 through 12 (44%) compared to patients treated with bupropion SR (30%) or placebo (17%).
The bupropion SR quit rate was also superior to placebo.
In addition, 29% of the Varenicline group were continuously abstinent from one week after TQD through the end of treatment as compared to 12% of the placebo group and 23% of the bupropion SR group.

● Similarly in Study 5, subjects treated with Varenicline had a superior rate of CO-confirmed abstinence during weeks 9 through 12 (44%) compared to patients treated with bupropion SR (30%) or placebo (18%).
The bupropion SR quit rate was also superior to placebo.
In addition, 29% of the Varenicline group were continuously abstinent from one week after TQD through the end of treatment as compared to 11% of the placebo group and 21% of the bupropion SR group.

Table 1: Continuous Abstinence, Week 9 through 12 (95% confidence interval) across different studies

Urge To Smoke
Based on responses to the Brief Questionnaire of Smoking Urges and the Minnesota Nicotine Withdrawal scale “Urge to Smoke” item, Varenicline reduced urge to smoke compared to placebo in all studies.

Long-Term Abstinence
Studies 1 through 5 included 40 weeks of post-treatment follow-up.
In each study, Varenicline treated patients were more likely to maintain abstinence throughout the follow-up period than were patients treated with placebo (Table 2).

Table 2: Continuous Abstinence, Weeks 9 through 52 (95% confidence interval) across different studies

* Study 6: This study assessed the effect of an additional 12 weeks of Varenicline therapy on the likelihood of long-term abstinence.
Patients in this study (n=1927) were treated with open-label Varenicline 1 mg BID for 12 weeks.
Patients who had stopped smoking by Week 12 were then randomized to double-blind treatment with Varenicline (1 mg BID) or placebo for an additional 12 weeks and then followed for 28 weeks post-treatment.

* The continuous abstinence rate from Week 13 through Week 24 was higher for subjects continuing treatment with Varenicline (70%) than for subjects switching to placebo (50%).
Superiority to placebo was also maintained during 28 weeks post-treatment follow-up (Varenicline 54% versus placebo 39%).