- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01480232
A Safety and Cognitive Function Study of EVP-6124 Versus Placebo in Subjects With Nicotine Dependence
February 21, 2017 updated by: A. Eden Evins
Proof-of-Concept Study of EVP-6124, an Alpha-7 Nicotinic Acetylcholine Receptor Agonist, Versus Placebo in Subjects With Nicotine Dependence
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
Study Overview
Status
Terminated
Conditions
Study Type
Interventional
Enrollment (Actual)
345
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: EVP-6124 + NicoDerm (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)
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One EVP-6124 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).
Brief, standard, manualized individual cognitive behavioral therapy intervention will be based on the Freedom from Smoking curriculum from the American Lung Association.
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Active Comparator: Placebo + NicoDerm (Active)
One placebo capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)
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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).
Brief, standard, manualized individual cognitive behavioral therapy intervention will be based on the Freedom from Smoking curriculum from the American Lung Association.
One placebo capsule ingested orally daily for 12 weeks (84 days)
|
Experimental: EVP-6124 + 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)
|
One EVP-6124 capsule ingested orally daily for 12 weeks (84 days)
Brief, standard, manualized individual cognitive behavioral therapy intervention will be based on the Freedom from Smoking curriculum from the American Lung Association.
One NRT patch (Placebo) daily for first 6 weeks (42 days).
|
Placebo Comparator: 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)
|
Brief, standard, manualized individual cognitive behavioral therapy intervention will be based on the Freedom from Smoking curriculum from the American Lung Association.
One placebo capsule ingested orally daily for 12 weeks (84 days)
One NRT patch (Placebo) daily for first 6 weeks (42 days).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence
Time Frame: Week 1, 2, 4, 6, 8, 10, 12
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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.
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Week 1, 2, 4, 6, 8, 10, 12
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Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point
Time Frame: Baseline, Weeks 1, 2, 4, 6, 8, 10, 12
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CO concentration was measured at every visit.
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Baseline, Weeks 1, 2, 4, 6, 8, 10, 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time
Time Frame: Baseline, week 1, week 12
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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.
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Baseline, week 1, week 12
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Safety and Tolerability of EVP-6124 Alone or Combined With NRT
Time Frame: Weeks 1-12
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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
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Weeks 1-12
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Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time
Time Frame: Baseline, week 1, week 12
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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)
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Baseline, week 1, week 12
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Anne Eden Evins, MD, MPH, Massachusetts General Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2011
Primary Completion (Actual)
September 1, 2015
Study Completion (Actual)
September 1, 2015
Study Registration Dates
First Submitted
November 23, 2011
First Submitted That Met QC Criteria
November 23, 2011
First Posted (Estimate)
November 28, 2011
Study Record Updates
Last Update Posted (Actual)
April 6, 2017
Last Update Submitted That Met QC Criteria
February 21, 2017
Last Verified
February 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Substance-Related Disorders
- Tobacco Use Disorder
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Cholinergic Agents
- Ganglionic Stimulants
- Nicotinic Agonists
- Cholinergic Agonists
- Nicotine
Other Study ID Numbers
- EVP-6124-014
- 1R01DA030992-01 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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