Clinical trial NCT01480232: A Safety and Cognitive Function Study of EVP-6124 Versus Placebo in Subjects With Nicotine Dependence
Official title: Proof-of-Concept Study of EVP-6124, an Alpha-7 Nicotinic Acetylcholine Receptor Agonist, Versus Placebo in Subjects With Nicotine Dependence
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Nicotine Dependence
Smoking Cessation
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: FORUM Pharmaceuticals Inc
name: National Institute on Drug Abuse (NIDA)
First posted: 2011-11-28
Enrollment: 345
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence
timeFrame: Week 1, 2, 4, 6, 8, 10, 12
measure: Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point
timeFrame: Baseline, Weeks 1, 2, 4, 6, 8, 10, 12
Secondary outcomes:
measure: Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time
timeFrame: Baseline, week 1, week 12
measure: Safety and Tolerability of EVP-6124 Alone or Combined With NRT
timeFrame: Weeks 1-12
measure: Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time
timeFrame: Baseline, week 1, week 12
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Anne Eden Evins, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Maurizio Fava, MD
role: PRINCIPAL_INVESTIGATOR
References: