A Safety and Cognitive Function Study of EVP-6124 Versus Placebo in Subjects With Nicotine Dependence
Condition: Nicotine Dependence; Smoking Cessation
MeSH terms: Tobacco Use Disorder
Intervention: EVP-6124; Placebo Capsule; NicoDerm Patch (Active); NRT Patch (Placebo); Brief Supportive and Behavioral Treatment
Intervention description: One EVP-6124 capsule ingested orally daily for 12 weeks (84 days); One placebo capsule ingested orally daily for 12 weeks (84 days); One NicoDerm patch once daily for first 6 weeks (42 days). Dosage will taper from 21 mg (Weeks 1-3) to 14 mg (Weeks 4-5) to 7 mg (Week 6).; One NRT patch (Placebo) daily for first 6 weeks (42 days).; Brief, standard, manualized individual cognitive behavioral therapy intervention will be based on the Freedom from Smoking curriculum from the American Lung Association.
Intervention MeSH terms: Nicotine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 345.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This study is designed to evaluate the initial evidence for efficacy of the investigational
      medicine, EVP-6124, to improve smoking cessation outcomes with and without a standard taper
      of nicotine replacement therapy (NRT) in healthy nicotine dependent smokers
    

Eligibility criteria:

        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