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

A. Eden Evins

Status and phase: Terminated; Phase 2

Conditions: Nicotine Dependence; Smoking Cessation

Treatments: Drug: EVP-6124; Drug: NicoDerm Patch (Active); Drug: Placebo Capsule; Behavioral: Brief Supportive and Behavioral Treatment; Drug: NRT Patch (Placebo)

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT01480232

EVP-6124-014

1R01DA030992-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Enrollment: 345 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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345 participants in 4 patient groups, including a placebo group

EVP-6124 + NicoDerm (Active)

Experimental group

Description:

One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)

Treatment:

Drug: EVP-6124

Drug: NicoDerm Patch (Active)

Behavioral: Brief Supportive and Behavioral Treatment

Placebo + NicoDerm (Active)

Active Comparator group

Description:

One placebo capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)

Treatment:

Drug: NicoDerm Patch (Active)

Drug: Placebo Capsule

Behavioral: Brief Supportive and Behavioral Treatment

EVP-6124 + NRT Patch (Placebo)

Experimental group

Description:

One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)

Treatment:

Drug: NRT Patch (Placebo)

Drug: EVP-6124

Behavioral: Brief Supportive and Behavioral Treatment

Placebo + NRT Patch (Placebo)

Placebo Comparator group

Description:

One placebo capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)

Treatment:

Drug: NRT Patch (Placebo)

Drug: Placebo Capsule

Behavioral: Brief Supportive and Behavioral Treatment