PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE MULTIPLE-DOSE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF VARENICLINE IN HEALTHY ADOLESCENT SMOKERS

Varenicline has been given to more than 3,000 adult cigarette smokers in other
studies. This drug is approved in the United States, Canada and Europe as an
aid to smoking cessation treatment in adults. Varenicline is a selective
nicotinic acetylcholine receptor (partial agonist), wich mediates the behavior
reinforcing eggects of nicotine. The therapeutic effect of varenicline offers
the therapeutic benefit of relieving symptoms of nicotine withdrawal and
cigarette craving during abstinence while blocking the reinforcing effects of
chronic nicotine. Phase 2 and 3 clinical trials have demonstrated the efficacy
and tolerability of varenicline 1 mg BID in more than 3000 cigarette smokers,
increasing the odds of quitting approximately 4-fold compared with placebo, and
nearly 2-fold compared with bupropion.

To characterize the multiple-dose pharmacokinetics of varenicline in adolescent
male
and female smoking subjects

This will be a double-blind, randomized, parallel group, placebo-controlled
study. A total of 70 adolescents 12-16 years of age, inclusive, enrolled and
completing the study will be targeted. Subjects will be required to be regular
smokers (smoking on a daily basis for at least the previous 3 months) and
having smoked an average of 3 cigarettes per day over the past 4 weeks. Dosing
will be determined based on your child*s body weight.). After determining the
weight group, your child will be randomly selected in the assigned dosisgroup:
High dose, low dose or placebo. The trial requirs total of 5 in-clinic visits.
The subject will be in the study for up to 46 days.

1) Low dose varenicline:
0.5 mg QD during 14 days [Regimen A] for the low weight group or
0.5 mg QD and 0.5 mg BID during 7 days [Regimen B] for the high weight group;

2) High dose varenicline:
0.5 mg QD and 0.5 mg BID during 7 days [Regimen B] for the low weight group or
0.5 mg QD during 3 days, 0.5 mg BID during 4 days, and 1 mg BID during 7 days
[Regimen C] for the high weight group;

3) or Placebo during 14 days

Patients may undergo serveral treatments, such as physical examination,
including measurement of the vital signs (blood pressure and heart rate),
collection of blood samples, pregnancy test and ECG. Patients will record the
number of cigarettes smoked during the in-patient stay on a Number of
Cigarettes Smoked Log.

Risks: Taking the drug varenicline may cause you to have nausea, sleep
disturbance, dizziness, constipation, flatulence (or gas) and/or vomiting.
Blood work may cause bleeding, pain, bruising, swelling and/or possible
infection at the site of the needle stick. It might be a risk of worsening the
smoking addiction as a result of not having active treatment for your child*s
smoking addiction.

Benefits: This study might not help you to quit smoking, but it may give
Pfizer information to help others to quit smoking.

Side effects: based on the experience of others who have received varenicline
are nausea, sleep disturbance, dizziness, constipation, flatulence (or gas) and
vomiting. Side effects may vary in severity depending on dosage level(s).