Comparison of Nicotine Inhaler and/or Bupropion in Helping People to Stop Smoking and Prevent the Recurrence of Smoking

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.

DISEASE CHARACTERISTICS: Currently smoking at least 10 cigarettes per day Smoked regularly
for the past year Motivated to use study medication More than 30 days since prior use of
tobacco products other than cigarettes (e.g., smokeless tobacco, pipes, cigars, or snuff)
No active chemical dependence of drug other than nicotine (e.g., alcohol, marijuana,
cocaine, heroin, or other illicit drugs) within the past year

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Not specified Life
expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not
specified Cardiovascular: No unstable angina, myocardial infarction, or cardiac
arrhythmias within the past 3 months Other: Not pregnant or nursing Negative pregnancy
test Fertile patients must use effective contraception for at least 3 months prior to and
during study Good health by medical history No history of seizure disorder No epilepsy No
prior serious head trauma or other predisposing factors to seizures (e.g., alcohol
withdrawal, febrile seizures during childhood, brain tumor, cerebrovascular accident, or
family history of idiopathic seizure disorder) No known hypersensitivity or allergy to
nicotine, menthol, or bupropion No prior or concurrent diagnosis of bulimia or anorexia
nervosa No other member of household currently enrolled on this study No bipolar disorder,
psychosis, or schizophrenia

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified
Endocrine therapy: More than 30 days since prior systemic steroids Radiotherapy: Not
specified Surgery: Not specified Other: More than 30 days since other prior behavioral or
pharmacologic smoking- cessation program (e.g., behavioral therapy, nicotine replacement
therapy, clonidine, bupropion, nortriptyline, or doxepin) More than 30 days since prior
investigational drugs More than 30 days since prior antipsychotics or antidepressants More
than 30 days since prior theophylline More than 30 days since prior monoamine oxidase
inhibitor More than 30 days since prior medication containing bupropion No concurrent
antiepileptic medications No concurrent medications known to lower seizure threshold No
other concurrent investigational drugs