Innovative Interventions for Smoking Cessation

The purpose of this study is to evaluate the effect of a combination of the 21 mg nicotine
patch and very low nicotine content cigarette (VLNC) compared to the VLNC cigarette alone or
21 mg nicotine patch alone on abstinence, time to relapse and toxicant levels.

The following primary hypothesis will be tested:

Abstinence rates will be highest and the time to relapse will be the longest in the VLNC
cigarettes plus nicotine patch condition compared to nicotine patch or VLNC cigarettes
alone.

Other hypotheses include:

1. Greater positive subjective responses to cigarettes will be observed with VLNC
cigarettes plus patch vs. VLNC cigarette;

2. Less drop-outs will be observed in the VLNC plus patch vs the other two conditions; and

3. Less compensatory smoking will be observed in the VLNC plus patch condition compared to
VLNC cigarette alone condition.

Cigarette smokers will be randomized to:

1. VLNC cigarettes (which provide sensory behavioral aspects of smoking but with limited
nicotine) plus nicotine patch for 6 weeks;

2. Nicotine patch for 6 weeks; or

3. VLNC cigarettes alone.

Outcome measures will include cessation assessed at the end of treatment as the primary
endpoint and at 36 weeks post-treatment, time to lapse and relapse to usual brand
cigarettes, and biomarkers of toxicant exposure. Predictors of abstinence and treatment
response for each of the treatment conditions will be explored.

Inclusion Criteria:

- a) Smoking at least 10 cigarettes daily for the past year;

- b) In good physical health;

- c) No contraindications for medicinal nicotine; and

- d) Stable, good mental health.

Exclusion Criteria:

- a) Subjects must not be using other tobacco or nicotine products.

- b) Female subjects cannot be pregnant or nursing and must be using appropriate birth
control.