Safety, Tolerability and Efficacy of the Nicotine Patch and Gum for the Treatment of Adolescent Tobacco Dependence

We hypothesize that two nicotine replacement delivery systems (patch and gum) are both safe
and efficacious for the treatment of adolescent nicotine dependence. Consequently, use of
both the patch and gum should be tolerable in this population with only minor adverse
side-effects. Secondly, some individuals in both groups (patch, gum) may benefit from either
cessation or reduction in smoke exposure, as a result of the distinctly different mechanisms
of the two treatments (steady state vs. intermittent delivery of NRT).

A.The primary objectives of this study are:

1. to evaluate the comparative safety of the nicotine transdermal system (21 mg "patch")
and the nicotine gum (2 mg and 4 mg), dosed appropriately to pre-treatment levels of
smoking, to initiate and sustain smoking cessation and reduction ;

2. to compare compliance levels with the patch and gum;

3. to evaluate the comparative efficacy of the patch and the gum to initiate and sustain
smoking cessation and reduction;

4. to compare the rates of biochemically-verified continuous abstinence by using
intent-to-treat analysis based on individual subject outcome.

B.The secondary objectives of this study are:

1. to correlate pre-treatment nicotine exposure (saliva cotinine) with withdrawal
intensity measured in all groups during treatment and with treatment outcome;

2. to compare biological markers of smoke exposure (expired air CO and saliva thiocyanate)
with self-reports of smoking and to correlate them with withdrawal symptomatology and
treatment outcome;

3. to obtain smoking topography data (puff volume, velocity of intake, interpuff interval,
and puffs per cigarette) on adolescent patterns of smoking as an index of smoking
intensity and exposure and to correlate pre-treatment smoking intensity with treatment
outcome.

C.The tertiary objectives are:

1. to examine the validity of the use of biochemical markers of smoke exposure (expired
air CO and saliva thiocyanate) as potential markers of smoking cessation in
adolescents;

2. to compare the relative cotinine exposure of adolescents who are smoking with those who
are receiving nicotine replacement who do and do not successfully quit

Inclusion Criteria:

- History of smoking 11 or more cigarettes per day (cpd) for at least one year

- Fagerström Test for Nicotine Dependence score of 5 and above

- General good health as verified by history, physical, psychiatric examination and
screening laboratory tests

Exclusion Criteria:

- History of cardiac disease

- Active dependence on any drug other than nicotine (as assessed by the DUSI)

- Current or past severe psychiatric disorders as per the Diagnostic Interview for
Children and Adolescents (DICA-A)

- Current use of tobacco or nicotine containing products other than cigarettes

- Previous use of any nicotine transdermal patch or nicotine gum

- Presence or history of severe skin allergies or dermatoses

- Pregnancy or lactation

- Active oral, dental or jaw mobility problems