Study to Determine if a New Nicotine Replacement Therapy Can Safely Help Smokers to Quit Smoking

This trial is a multi-center, randomized, double blind, placebo-controlled parallel group
study to measure the efficacy and safety of a new nicotine replacement therapy for smoking
cessation in a naturalistic environment. Subjects will be randomized in a 2:1 ratio (active
to placebo). It is anticipated that data from about 450 in the active treatment group at
Week 12 will be required for the safety analysis. In order to obtain that number of
subjects, approximately 1500 subjects will need to be enrolled into the Use phase of the
study, 1000 in the active arm and 500 in the placebo arm.

Based on the directions for use on the Drug Facts label, the study will include six weeks of
full study drug treatment and then six weeks of progressive tapering drug treatment (Weeks
1-12). There will be a 14-week post-use follow up period.

This trial will be conducted in three sequential phases: Enrollment (baseline), Use and
Post-use Follow-up. The Enrollment Phase will be conducted in approximately 20 pharmacies
in nine diverse geographical areas in the continental United States. Subjects who qualify
to participate in the study will be given three units of investigational product, a subject
diary for tracking investigational product use and a medical problems worksheet to assist in
the collection of AE information. Subjects will also be given a small hand counter and will
be encouraged to use it to help keep track of the number of doses they use each day.
Subjects will also be given a card with contact information for the pharmacy and study
nurses. Where needed, the subject can also speak with the study physician.

During the Use Phase, the collection of data related to efficacy will be accomplished during
four return visits to the pharmacy (at weeks 2, 4, 6 and 12). Self-reported abstinence will
be verified by carbon monoxide (CO) measurements obtained at each pharmacy visit. Subjects
will be given a subject use diary at each follow-up and re-supply visit and completed
diaries will be collected each time the subject returns to the pharmacy. Subjects can
return to the pharmacy for additional supplies at any time during their participation.
Empty units will be returned during these visits.

Safety data will be collected during four telephone interviews, conducted by trained nurse
interviewers, at weeks 2, 4, 6 and 12. If a subject reports an adverse event during a visit
(return visit or resupply visit), this information will be immediately forwarded to the
nurse interviewers for follow-up. Subjects may also initiate a call to the study nurses
themselves to discuss health problems. All AE information collected will be reviewed by a
physician as the adverse events are collected. A standardized visual mouth examination will
be conducted by trained dentists at the enrollment visit and at the Week 12 return visit.

During the Post-use Follow-up period, self-reported efficacy and safety data will be
collected during two telephone interviews initiated by trained nurse interviewers (at weeks
16 and 26). Subjects reporting abstinence since the last visit or abstinence for the prior
seven days during these two interviews will be asked to return to the pharmacy to verify
abstinence with an exhaled CO measurement. An additional telephone interview will be
conducted between Week-12 and Week-16, by trained nurse interviewers, who will administer
the End of Treatment questions to those subjects who have reported the following product use
behavior that are inconsistent with the directions on the Drug Facts label: Use of more than
64 doses in a 24-hour period at least one time or use of more than 4 doses per hour at least
one time based on the diary or their self report.