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 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 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 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 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