Trial Information

Phase III Trial Comparing Nicotine Inhaler Versus Bupropion Versus Nicotine Inhaler Plus Bupropion For Smoking Cessation Efficacy And Relapse Prevention

OBJECTIVES: I. Compare the effectiveness of nicotine inhaler vs bupropion vs nicotine
inhaler plus bupropion on smoking cessation and prevention of relapse in participants who
currently smoke. II. Compare the reduction in the rate of relapse to smoking after initial
abstinence in participants treated long term with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to gender, cigarettes smoked per day at time of screening (10-39 vs
40 or more), and total length of smoking in years (less than 5 vs 5-9 vs 10 or more).
Participants are randomized to one of three treatment arms. Arm I: Participants receive 6-16
nicotine inhaler cartridges per day. Arm II: Participants receive oral bupropion 1-2 times
daily. Arm III: Participants receive 6-16 nicotine inhaler cartridges per day and oral
bupropion 1-2 times daily. In all arms, treatment continues for 12 weeks. After 12 weeks,
participants are randomized a second time based on whether they continue to smoke or are
smoke-free. Participants randomized to arm I who continue to smoke are randomized to one of
two treatment arms. Arm IV: Participants receive oral bupropion 1-2 times daily for 12 weeks
Arm V: Participants receive oral placebo 1-2 times daily for 12 weeks. Participants
randomized to arm II who continue to smoke are randomized to one of two treatment arms. Arm
VI: Participants receive 6-16 nicotine inhaler cartridges per day for 12 weeks. Arm VII:
Participants receive 6-16 placebo inhaler cartridges per day for 12 weeks. Participants
randomized to arm III who continue to smoke do not receive any further therapy. Participants
randomized to arm I who are smoke-free are randomized to one of two treatment arms. Arm
VIII: Participants receive 6-16 nicotine inhaler cartridges per day for 40 weeks. Arm IX:
Participants receive 6-16 placebo inhaler cartridges per day for 40 weeks. Participants
randomized to arm II who are smoke-free are randomized to one of two treatment arms. Arm X:
Participants receive oral bupropion 1-2 times daily for 40 weeks. Arm XI: Participants
receive oral placebo 1-2 times daily for 40 weeks. Participants randomized to arm III who
are smoke-free are randomized to one of four treatment arms. Arm XII: Participants receive
6-16 nicotine inhaler cartridges per day and oral placebo 1-2 times daily for 40 weeks. Arm
XIII: Participants receive 6-16 placebo inhaler cartridges per day and oral bupropion 1-2
times daily for 40 weeks. Arm XIV: Participants receive 6-16 nicotine inhaler cartridges per
day and oral bupropion 1-2 times daily for 40 weeks. Arm XV: Participants receive 6-16
placebo inhaler cartridges per day and oral placebo 1-2 times daily for 40 weeks. All
participants are followed every month for 6 months.

PROJECTED ACCRUAL: Approximately 1850 participants (616 per treatment arm of the initial
randomization) will be accrued for this study within 6 months.