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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Massachusetts General Hospital
Sponsor:
Collaborators:
FORUM Pharmaceuticals Inc
Information provided by (Responsible Party):
A. Eden Evins, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01480232
First received: November 23, 2011
Last updated: May 14, 2013
Last verified: May 2013
  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 CQ Patch (Active)
Drug: NRT Patch (Placebo)
Behavioral: Brief Supportive and Behavioral Treatment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, 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 Massachusetts General Hospital:

Primary Outcome Measures:
  • Effects of EVP-6124 on 7-day point-prevalence smoking abstinence [ Time Frame: Weeks 1-12 ] [ Designated as safety issue: No ]
    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 CO concentration [ Time Frame: Weeks 1-12 ] [ Designated as safety issue: No ]
    CO concentration over time will be plotted to determine whether there is variation in the effect of EVP-6124, using a random effect model.


Secondary Outcome Measures:
  • Effects of EVP-6124 on cognitive performance [ Time Frame: Weeks 1-12 ] [ Designated as safety issue: No ]
    Cognitive performance will be measured using the N-Back Task, Stroop Task, Cambridge Neuropsychological Test Automated Battery, Smoking Emotional Stroop Task, and the Continuous Performance Test - Conners Version. Additional testing will include nicotine craving and withdrawal assessments (Tiffany Questionnaire of Smoking Urges and Wisconsin Smoking Withdrawal Scale) and psychological efficacy assessments (Positive and Negative Affect Scale, Center for Epidemiologic Studies-Depression [CES-D] Scale, and the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire).

  • Safety and tolerability of EVP-6124 alone or combined with NRT [ Time Frame: Weeks 1-14 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 450
Study Start Date: December 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EVP-6124 + NicoDerm CQ (Active)
One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm CQ 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 CQ Patch (Active)
One NicoDerm CQ 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 CQ (Active)
One placebo capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm CQ 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 CQ Patch (Active)
One NicoDerm CQ 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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Self-report of smoking an average of ≥10 cigarettes/day for 6 months and expired CO ≥10 parts per million (ppm) or urine cotinine ≥100 ng/mL at screening
  • Self-report of smoking first cigarette of the day within 30 minutes of awakening
  • 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 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 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 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

Contacts
Contact: Vicenta B. Hudziak, BA 617-724-8472 a7smoking@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
A. Eden Evins
FORUM Pharmaceuticals Inc
Investigators
Principal Investigator: Anne Eden Evins, MD, MPH Massachusetts General Hospital
Principal Investigator: Maurizio Fava, MD Massachusetts General Hospital
  More Information

No publications provided

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
Study First Received: November 23, 2011
Last Updated: May 14, 2013
Health Authority: United States: Food and Drug Administration

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
Pharmacologic Actions
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014