The efficacy of CHANTIX 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 CHANTIX. 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 CHANTIX 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 CHANTIX to
placebo. This study provided initial evidence that CHANTIX 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 CHANTIX 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.
CHANTIX was given in two divided doses. Each dose of CHANTIX 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 CHANTIX 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 (Figure 1). 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 CHANTIX 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 CHANTIX, 40% had CO-confirmed continuous
abstinence during weeks 9 through 12 compared to 12% in the placebo group.
In addition, 29% of the CHANTIX 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 CHANTIX
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 CHANTIX 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 CHANTIX 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 CHANTIX 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 CHANTIX 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 CHANTIX 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.
Figure 1: Continuous Abstinence, Weeks 9 through 12
Table 1: Continuous Abstinence, Weeks 9 through 12 (95% confidence
interval) across different studies
Urge To Smoke
Long-Term Abstinence
Figure 2: Continuous Abstinence, Weeks 9 through 52
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
CHANTIX therapy on the likelihood of long-term abstinence. Patients in this
study (n=1927) were treated with open-label CHANTIX 1 mg BID for 12 weeks.
Patients who had stopped smoking by Week 12 were then randomized to double-blind
treatment with CHANTIX (1 mg BID) or placebo for an additional 12 weeks
and then followed for
The continuous abstinence rate from Week 13 through Week 24 was higher
for subjects continuing treatment with CHANTIX (70%) than for subjects switching
to placebo (50%). Superiority to placebo was also maintained during 28 weeks
post-treatment follow-up (CHANTIX 54% versus placebo 39%).
In Figure 3 below, the x-axis represents the study week for each observation
allowing a comparison of groups at similar times after discontinuation of
CHANTIX. Post-CHANTIX follow-up begins at Week 13 for the placebo group
and Week 25 for the CHANTIX group. The y-axis represents the percent of
subjects who had been abstinent for the last week of CHANTIX treatment and
remained abstinent at the given timepoint.
Figure 3: Continuous Abstinence Rate during nontreatment follow-up