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

Primary Purpose

Nicotine Dependence, Smoking Cessation

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
EVP-6124
Placebo Capsule
NicoDerm Patch (Active)
NRT Patch (Placebo)
Brief Supportive and Behavioral Treatment
Sponsored by
A. Eden Evins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nicotine Dependence

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Placebo Comparator

Arm Label

EVP-6124 + NicoDerm (Active)

Placebo + NicoDerm (Active)

EVP-6124 + NRT Patch (Placebo)

Placebo + NRT Patch (Placebo)

Arm Description

One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)

One placebo capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)

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 placebo capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)

Outcomes

Primary Outcome Measures

Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence
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
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
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
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
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)

Full Information

First Posted
November 23, 2011
Last Updated
February 21, 2017
Sponsor
A. Eden Evins
Collaborators
FORUM Pharmaceuticals Inc, National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT01480232
Brief Title
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

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Terminated
Why Stopped
Study has been put on clinical hold by FDA
Study Start Date
December 2011 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
A. Eden Evins
Collaborators
FORUM Pharmaceuticals Inc, National Institute on Drug Abuse (NIDA)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nicotine Dependence, Smoking Cessation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
345 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EVP-6124 + NicoDerm (Active)
Arm Type
Experimental
Arm Description
One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)
Arm Title
Placebo + NicoDerm (Active)
Arm Type
Active Comparator
Arm Description
One placebo capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)
Arm Title
EVP-6124 + NRT Patch (Placebo)
Arm Type
Experimental
Arm Description
One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)
Arm Title
Placebo + NRT Patch (Placebo)
Arm Type
Placebo Comparator
Arm Description
One placebo capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)
Intervention Type
Drug
Intervention Name(s)
EVP-6124
Intervention Description
One EVP-6124 capsule ingested orally daily for 12 weeks (84 days)
Intervention Type
Drug
Intervention Name(s)
Placebo Capsule
Intervention Description
One placebo capsule ingested orally daily for 12 weeks (84 days)
Intervention Type
Drug
Intervention Name(s)
NicoDerm Patch (Active)
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
NRT Patch (Placebo)
Intervention Description
One NRT patch (Placebo) daily for first 6 weeks (42 days).
Intervention Type
Behavioral
Intervention Name(s)
Brief Supportive and Behavioral Treatment
Intervention Description
Brief, standard, manualized individual cognitive behavioral therapy intervention will be based on the Freedom from Smoking curriculum from the American Lung Association.
Primary Outcome Measure Information:
Title
Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence
Description
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.
Time Frame
Week 1, 2, 4, 6, 8, 10, 12
Title
Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point
Description
CO concentration was measured at every visit.
Time Frame
Baseline, Weeks 1, 2, 4, 6, 8, 10, 12
Secondary Outcome Measure Information:
Title
Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time
Description
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.
Time Frame
Baseline, week 1, week 12
Title
Safety and Tolerability of EVP-6124 Alone or Combined With NRT
Description
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
Time Frame
Weeks 1-12
Title
Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time
Description
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)
Time Frame
Baseline, week 1, week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Eden Evins, MD, MPH
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Maurizio Fava, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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