Effects of EVT 302 With or Without NRT on Craving and Withdrawal in Healthy Male Smokers Deprived of Cigarettes

Inclusion criteria

• Male subjects between 18 and 55 years of age, inclusive
• BMI between 18 and 30, minimum weight of 50 kg
• Negative urine drug & alcohol screen
• Able to comply with tyramine-restricted diet
• Smoking of ≥17 and ≤34 cigarettes per day for the past year and have not tried to quit smoking in the 3 months prior to screening
• Subjects are willing and able to quit for about 12 hours in each of three subsequent study periods
• Previous experience of craving following smoking cessation
• Breath CO between 15 ppm and 20 ppm and cotinine in saliva and plasma at least 250 ng/mL at screening
• Liver function test results not above 1.5 times the upper normal limit (UNL) at screening visit and at re-assessment during the study.

Exclusion criteria

• Participation in another clinical study within 60 days of screening
• Evidence of active significant psychiatric or neurological disease or dependency other than cigarettes
• Are known to have or are a carrier of the hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, has a positive result to the human immunodeficiency virus-1 and/or 2 (HIV-1 and/or HIV-2) antibodies
• Known hypersensitivity to MAO inhibitors or any substance that is contained in the study formulations
• Known allergy to plasters or NRT patches
• Previous participation in another study with EVT 302
• Currently receiving treatment for smoking cessation
• Current use of tobacco products other than cigarettes
• Require treatment with any medication
• Subject with a clinically relevant abnormal 12-lead ECG recording or QTcB/F >430 ms
• Use of a prescription medicine within 14 days or 5 half-lives, whichever is the longer, of the start of dosing, or use of an over-the-counter medication during the 7 days before the study, including herbal remedies, but excluding paracetamol and vitamin supplements (provided intake does not exceed the daily recommended allowance)
• Subjects must not be planning to father a child or donate sperm, during the study and 3 months after the end of the study. Acceptable methods of contraception comprise barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive since at least 2 month)
• Daily consumption of more than 5 cups of tea or coffee, or more than 1.0 litre of xanthine-containing drinks
• Recent myocardial infarction, unstable or worsening angina pectoris, prince metal angina, severe arrhythmias, recent stroke.
• Creatinine clearance (CLR) calculated according to the formula by Modification of Diet in Renal Disease (MDRD) of <80 mL/min