Multiple Dose, Dose Escalation Study of Varenicline Controlled Release Formulation in Adult Smokers

• Drug: Varenicline Tartrate
  
  Varenicline 1.8 mg AMT-8 controlled release tablets administered twice a day for 14 days.
• Drug: Varenicline Tartrate
  
  Planned dose is Varenicline 2.4 mg AMT-8 controlled release tablets administered twice a day for 14 days. Actual dose may be adjusted based on emerging data from prior dose cohorts.
• Drug: Varenicline Tartrate
  
  Planned dose is Varenicline 3 mg AMT-8 controlled release tablets administered twice a day for 14 days. Actual dose may be adjusted based on emerging data from prior dose cohorts.
• Drug: Varenicline Tartrate
  
  The dose to be administered is not yet determined and will be based on emerging data from prior dose cohorts. The dose will be administered as Varenicline AMT-8 controlled release tablets twice a day for 14 days. The doses to be tested may be lower, higher or repeat a previously tested dose and may include a titration.

• Cohort 1
  
  Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3).
  Intervention: Drug: Varenicline Tartrate
• Cohort 2
  
  Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3).
  Intervention: Drug: Varenicline Tartrate
• Cohort 3
  
  Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3).
  Intervention: Drug: Varenicline Tartrate
• Optional Cohort 4
  
  Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3).
  Intervention: Drug: Varenicline Tartrate
• Optional Cohort 5
  
  Subjects will be randomized to receive either experimental drug (N=9) or matching placebo (N=3).
  Intervention: Drug: Varenicline Tartrate

Inclusion Criteria:

• Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12 lead ECG and clinical laboratory tests.
• Currently smoking and have smoked an average of at least 10 cigarettes per day during the past year, with no period of abstinence greater than 3 continuous months in the past year.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
• Pregnant or nursing women are excluded; women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception as outlined in the protocol from at least 14 days prior to study medication administration until completion of protocol-required procedures are excluded.
• Subjects with an estimated creatinine clearance (CLcr) <80 mL/min derived using the method of Cockcroft and Gault.