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

Phase 2

Terminated

Conditions: Nicotine Dependence
Smoking Cessation

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

Registration Number: NCT01480232

Lead Sponsor: A. Eden Evins

Brief 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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 345

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + NRT Patch (Placebo)	NRT Patch (Placebo)	One placebo capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)
EVP-6124 + NicoDerm (Active)	NicoDerm Patch (Active)	One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)
EVP-6124 + NicoDerm (Active)	Brief Supportive and Behavioral Treatment	One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)
Placebo + NicoDerm (Active)	Brief Supportive and Behavioral Treatment	One placebo capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)
Placebo + NRT Patch (Placebo)	Placebo Capsule	One placebo capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)
EVP-6124 + NRT Patch (Placebo)	EVP-6124	One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)
EVP-6124 + NicoDerm (Active)	EVP-6124	One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)
Placebo + NicoDerm (Active)	Placebo Capsule	One placebo capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)
EVP-6124 + NRT Patch (Placebo)	NRT Patch (Placebo)	One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)
EVP-6124 + NRT Patch (Placebo)	Brief Supportive and Behavioral Treatment	One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)
Placebo + NicoDerm (Active)	NicoDerm Patch (Active)	One placebo capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)
Placebo + NRT Patch (Placebo)	Brief Supportive and Behavioral Treatment	One placebo capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)

Primary Outcome Measures

Name	Time	Method
Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence	Week 1, 2, 4, 6, 8, 10, 12	Smoking abstinence is defined as a self-report of smoking no cigarettes for the past 7 days by time-line follow-back, confirmed by expired carbon monoxide (CO) \<10 ppm and/or urine cotinine \<50 ng/mL.
Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point	Baseline, Weeks 1, 2, 4, 6, 8, 10, 12	CO concentration was measured at every visit.

Secondary Outcome Measures

Name	Time	Method
Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time	Baseline, week 1, week 12	The Continuous Performance Test (CPT) is a measure of both vigilance/attentional control and response inhibition. During the task, subjects are required to press a button whenever a letter appears on the screen unless that letter is an 'X'. Measures of attentional control will serve as primary measure from this test. Baseline attentional impairment is associated with reduced odds of abstinence, abstinence differentially worsens performance on this measure in those with baseline attentional impairment, and NRT improves performance on a similar measure.
Safety and Tolerability of EVP-6124 Alone or Combined With NRT	Weeks 1-12	All AEs (adverse experiences) spontaneously reported by subjects and/or observed by investigator and evaluation of physical examinations, prior and concomitant medications, clinical laboratory tests, ECGs, and vital signs measurements. Data was collected at every visit and was analyzed as aggregate at the end of week 12
Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time	Baseline, week 1, week 12	This task is a standard measure that can assess working memory performance under varying levels of task demand. Subjects are presented with a stream of stimuli, and the task is to decide for each stimulus whether it matches the one presented N items before. The processing load can be varied systematically by manipulating the value of N, which is expressed with changes in accuracy and reaction time. The number of errors as well as reaction times increase monotonically with increasing levels of N. The n-back task is sensitive to nicotine administration and abstinence effects. Here we present reaction time (RT)

Trial Locations

Locations (1): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States