A Safety and Cognitive Function Study of EVP-6124 Versus Placebo in Subjects With Nicotine Dependence

Inclusion Criteria: * Self-report of smoking an average of ≥10 cigarettes/day for 6 months and expired carbon monoxide (CO) ≥10 parts per million (ppm) or urine cotinine ≥ 100 ng/mL at screening or self-report of smoking an average of 5-9 cigarettes/day for 6 months and a urine cotinine ≥30ng/ml at screening * Have a negative urine drug screen at screening * Fertile, sexually active subjects (males and females) must use an effective method of contraception from the first dose of study drug and for 3 months after the last dose of study drug * If female and capable of conception, must have a negative urine Human chorionic gonadotrophin (hCG) pregnancy test at screening and Day 1 Exclusion Criteria: * Have unstable medical illness with hospitalization for treatment likely within 6 months * Have life-threatening arrhythmia, cerebrovascular or cardiovascular event within 6 months of enrollment * Have liver function tests elevated \>2.5 times the upper limit of normal range * Have a tumor or a seizure disorder * Currently using other tobacco- or nicotine-containing products and unwilling to try to quit * Have a 6-month history of substance use disorder other than nicotine or caffeine or major depressive disorder * Have a history of multiple adverse drug reactions * Non-response (past 3 months) to nicotine replacement therapy (NRT) \>20 mg/day, bupropion \>150 mg/day, or varenicline 2 mg/day for ≥4 weeks * Use of excluded concomitant medications * Hospitalization for any reason within 30 days of screening * Use of any investigational drug or device within 30 days of screening * Have clinically significant abnormal serum electrolytes * Have insufficiently controlled diabetes mellitus * Have renal insufficiency (serum creatinine \>1.8 mg/dL) * Malignant tumor within the last 5 years, with the exception of squamous and basal cell carcinoma or cervical carcinoma in situ * Have a clinically significant cardiovascular abnormality on the screening EKG * Lifetime history of schizophrenia, bipolar disorder, post-traumatic stress disorder, bulimia, organic mental disorder, dementia, pervasive developmental disorder * Have untreated, clinically significant hypothyroidism or hyperthyroidism * Have a positive self-report of human immunodeficiency virus infection * Females who are pregnant or nursing * Any experimental drug currently or within 30 days before baseline * Have a serious risk of suicide * Have a screening electrocardiogram (ECG) with a corrected QT (QTc) interval using Bazett's formula \>450 msec for males and \>470 msec for females or the presence of any clinically significant cardiac abnormalities