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

This study has been terminated.
(Study has been put on clinical hold by FDA)
Sponsor:
Collaborators:
FORUM Pharmaceuticals Inc
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
A. Eden Evins, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01480232
First received: November 23, 2011
Last updated: February 21, 2017
Last verified: February 2017
  Purpose
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

Condition Intervention Phase
Nicotine Dependence Smoking Cessation Drug: EVP-6124 Drug: Placebo Capsule Drug: NicoDerm Patch (Active) Drug: NRT Patch (Placebo) Behavioral: Brief Supportive and Behavioral Treatment Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Proof-of-Concept Study of EVP-6124, an Alpha-7 Nicotinic Acetylcholine Receptor Agonist, Versus Placebo in Subjects With Nicotine Dependence

Resource links provided by NLM:


Further study details as provided by A. Eden Evins, Massachusetts General Hospital:

Primary Outcome Measures:
  • Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence [ Time Frame: 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 [ Time Frame: Baseline, Weeks 1, 2, 4, 6, 8, 10, 12 ]
    CO concentration was measured at every visit.


Secondary Outcome Measures:
  • Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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)


Enrollment: 345
Study Start Date: December 2011
Study Completion Date: September 2015
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
Drug: EVP-6124
One EVP-6124 capsule ingested orally daily for 12 weeks (84 days)
Drug: NicoDerm Patch (Active)
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).
Behavioral: Brief Supportive and Behavioral Treatment
Brief, standard, manualized individual cognitive behavioral therapy intervention will be based on the Freedom from Smoking curriculum from the American Lung Association.
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)
Drug: Placebo Capsule
One placebo capsule ingested orally daily for 12 weeks (84 days)
Drug: NicoDerm Patch (Active)
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).
Behavioral: Brief Supportive and Behavioral Treatment
Brief, standard, manualized individual cognitive behavioral therapy intervention will be based on the Freedom from Smoking curriculum from the American Lung Association.
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)
Drug: EVP-6124
One EVP-6124 capsule ingested orally daily for 12 weeks (84 days)
Drug: NRT Patch (Placebo)
One NRT patch (Placebo) daily for first 6 weeks (42 days).
Behavioral: Brief Supportive and Behavioral Treatment
Brief, standard, manualized individual cognitive behavioral therapy intervention will be based on the Freedom from Smoking curriculum from the American Lung Association.
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)
Drug: Placebo Capsule
One placebo capsule ingested orally daily for 12 weeks (84 days)
Drug: NRT Patch (Placebo)
One NRT patch (Placebo) daily for first 6 weeks (42 days).
Behavioral: Brief Supportive and Behavioral Treatment
Brief, standard, manualized individual cognitive behavioral therapy intervention will be based on the Freedom from Smoking curriculum from the American Lung Association.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01480232

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
A. Eden Evins
FORUM Pharmaceuticals Inc
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator: Anne Eden Evins, MD, MPH Massachusetts General Hospital
Principal Investigator: Maurizio Fava, MD Massachusetts General Hospital
  More Information

Responsible Party: A. Eden Evins, Director, Center for Addiction Medicine Massachusetts General Hospital, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01480232     History of Changes
Other Study ID Numbers: EVP-6124-014
1R01DA030992-01 ( U.S. NIH Grant/Contract )
Study First Received: November 23, 2011
Results First Received: December 15, 2016
Last Updated: February 21, 2017

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Nicotine
Nicotinic Agonists
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2017