Nicotine DependencePhase 2NCT01480232

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

A Phase 2 study testing EVP-6124, NicoDerm Patch (Active) and Brief Supportive and Behavioral Treatment in people with Nicotine Dependence and Smoking Cessation, run by A. Eden Evins at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial 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 Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Nicotine Dependence, Smoking Cessation
What is being tested?: EVP-6124, NicoDerm Patch (Active) and Brief Supportive and Behavioral Treatment
Type of treatment: Pill or oral medicine, Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 345 participants
Where: 1 siteUnited States
Study dates: Dec 2011to Sep 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 23Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Massachusetts General Hospital
Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: Proof-of-Concept Study of EVP-6124, an Alpha-7 Nicotinic Acetylcholine Receptor Agonist, Versus Placebo in Subjects With Nicotine Dependence

Conditions: Nicotine Dependence, Smoking Cessation
Being tested: EVP-6124, Placebo Capsule, NicoDerm Patch (Active), NRT Patch (Placebo), Brief Supportive and Behavioral Treatment
Medical subject headings: Tobacco Use Disorder, Smoking Cessation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EVP-6124Drug
One EVP-6124 capsule ingested orally daily for 12 weeks (84 days)
Placebo CapsuleDrug
One placebo capsule ingested orally daily for 12 weeks (84 days)
NicoDerm Patch (Active)Drug
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).
NRT Patch (Placebo)Drug
One NRT patch (Placebo) daily for first 6 weeks (42 days).
Brief Supportive and Behavioral TreatmentBehavioural
Brief, standard, manualized individual cognitive behavioral therapy intervention will be based on the Freedom from Smoking curriculum from the American Lung Association.

Study groups in NCT01480232
Study group	Role	What they receive
EVP-6124 + NicoDerm (Active)	Experimental	One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days) Receives: Drug: EVP-6124; Drug: NicoDerm Patch (Active); Behavioral: Brief Supportive and Behavioral Treatment
Placebo + NicoDerm (Active)	Active comparator	One placebo capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days) Receives: Drug: Placebo Capsule; Drug: NicoDerm Patch (Active); Behavioral: Brief Supportive and Behavioral Treatment
EVP-6124 + NRT Patch (Placebo)	Experimental	One EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days) Receives: Drug: EVP-6124; Drug: NRT Patch (Placebo); Behavioral: Brief Supportive and Behavioral Treatment
Placebo + NRT Patch (Placebo)	Placebo comparator	One placebo capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days) Receives: Drug: Placebo Capsule; Drug: NRT Patch (Placebo); Behavioral: Brief Supportive and Behavioral Treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Week 1, 2, 4, 6, 8, 10, 12
Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point
CO concentration was measured at every visit.
Measured: Baseline, Weeks 1, 2, 4, 6, 8, 10, 12

Secondary outcomes (3)

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.
Measured: Baseline, week 1, week 12
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
Measured: Weeks 1-12
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)
Measured: Baseline, week 1, week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2011Sep 2015

First posted28 Nov 2011 (estimated)
Study startDec 2011
Primary completionSep 2015
Study completionSep 2015

Why it stopped: Study has been put on clinical hold by FDA

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Nicotine DependenceStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 345 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01480232
Sponsor's protocol ID: EVP-6124-014
Other IDs: 1R01DA030992-01
Status last verified: Feb 2017
First submitted: 23 Nov 2011
Last updated: 6 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Advanced Functional and Structural MRI Techniques for Neuropharmacological Imaging
Drug Abuse, Nicotine Dependence
Not yet recruiting
Quit With Sense: Using Mindful Smoking and Wearable Device for Smoking Cessation
Smoking Cessation, Cigarette Smoking
Recruiting
Adapting and Pilot Testing a Skills-based Smoking Cessation Intervention to Address Developmental and Health-related Stress Among Adults Who Smoke
Smoking Cessation, Depression
Not yet recruitingPhase 2
Effects of Psilocybin on Craving in Nicotine Dependence
Nicotine Dependence
Not yet recruitingObservational study
Prevalence and Association of Dysfunctional Breathing With Nicotine Dependence and Physical Activity Among Young Smokers
Dysfunctional Breathing, Physical Activity

All Nicotine Dependence trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Proof-of-Concept Study of EVP-6124, an Alpha-7 Nicotinic Acetylcholine Receptor Agonist, Versus Placebo in Subjects With Nicotine Dependence
ClinicalTrials.gov ID: NCT01480232
Acronym / sponsor ID: EVP-6124-014
Conditions: Nicotine Dependence, Smoking Cessation
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study has been put on clinical hold by FDA
Enrolment: 345 participants (actual)
Lead sponsor: A. Eden EvinsUniversity, hospital or other
Collaborators: FORUM Pharmaceuticals Inc, National Institute on Drug Abuse (NIDA)
Study start: Dec 2011
Primary completion: Sep 2015 (actual)
Study completion: Sep 2015 (actual)
First posted: 28 Nov 2011 (estimated)
Results: Posted 6 Apr 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
EVP-6124 + NicoDerm (Active)	Experimental	Drug: EVP-6124, Drug: NicoDerm Patch (Active), Behavioral: Brief Supportive and Behavioral TreatmentOne EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)
Placebo + NicoDerm (Active)	Active comparator	Drug: Placebo Capsule, Drug: NicoDerm Patch (Active), Behavioral: Brief Supportive and Behavioral TreatmentOne placebo capsule ingested orally daily for 12 weeks (84 days) and one NicoDerm patch (Active) daily for first 6 weeks (42 days)
EVP-6124 + NRT Patch (Placebo)	Experimental	Drug: EVP-6124, Drug: NRT Patch (Placebo), Behavioral: Brief Supportive and Behavioral TreatmentOne EVP-6124 capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)
Placebo + NRT Patch (Placebo)	Placebo comparator	Drug: Placebo Capsule, Drug: NRT Patch (Placebo), Behavioral: Brief Supportive and Behavioral TreatmentOne placebo capsule ingested orally daily for 12 weeks (84 days) and one NRT patch (Placebo) daily for first 6 weeks (42 days)

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (23 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EVP-6124One EVP-6124 capsule ingested orally daily for 12 weeks (84 days)	Drug	EVP-6124 + NRT Patch (Placebo), EVP-6124 + NicoDerm (Active)
Placebo CapsuleOne placebo capsule ingested orally daily for 12 weeks (84 days)	Drug	Placebo + NRT Patch (Placebo), Placebo + NicoDerm (Active)
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).	Drug	EVP-6124 + NicoDerm (Active), Placebo + NicoDerm (Active)
NRT Patch (Placebo)One NRT patch (Placebo) daily for first 6 weeks (42 days).	Drug	EVP-6124 + NRT Patch (Placebo), Placebo + NRT Patch (Placebo)
Brief Supportive and Behavioral TreatmentBrief, standard, manualized individual cognitive behavioral therapy intervention will be based on the Freedom from Smoking curriculum from the American Lung Association.	Behavioural	EVP-6124 + NRT Patch (Placebo), EVP-6124 + NicoDerm (Active), Placebo + NRT Patch (Placebo), Placebo + NicoDerm (Active)

Primary outcome

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.

3 secondary outcomes

Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time
Time frame: Baseline, week 1, week 12
Safety and Tolerability of EVP-6124 Alone or Combined With NRT
Time frame: Weeks 1-12
Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time
Time frame: Baseline, week 1, week 12

Results and safety

Results posted to the registry on 6 Apr 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
EVP-6124 + NicoDerm (Active)	40	22
EVP-6124 + NRT Patch (Placebo)	41	19
Placebo + NicoDerm (Active)	38	21
Placebo + NRT Patch (Placebo)	41	22

Primary outcome: Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence

Time frame: Week 1, 2, 4, 6, 8, 10, 12. Number. Unit: % participants with 7-Day Point Prevalen

Measure	EVP-6124 + NicoDerm CQ (Active) n = 40	EVP-6124 + NRT Patch (Placebo) n = 41	Placebo + NicoDerm CQ (Active) n = 38	Placebo + NRT Patch (Placebo) n = 41
Seven-Day Point Prevalence Abstinence Rate week 1	25.0	12.2	28.9	17.1
Seven-Day Point Prevalence Abstinence Rate week 2	47.5	19.5	42.1	24.4
Seven-Day Point Prevalence Abstinence Rate week 4	40.0	17.1	44.7	19.5
Seven-Day Point Prevalence Abstinence Rate week 6	52.5	14.6	34.2	22.0
Seven-Day Point Prevalence Abstinence Rate week 8	37.5	14.6	28.9	24.4
Seven-Day Point Prevalence Abstinence Rate week 10	37.5	12.2	23.7	24.4
Seven-Day Point Prevalence Abstinence Rate week 12	25.0	12.2	18.4	19.5

Population analysed: The primary smoking cessation variable is biochemically verified self-report of 7-day point prevalence abstinence at 12 weeks (end of treatment).

Primary outcome: Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point

Time frame: Baseline, Weeks 1, 2, 4, 6, 8, 10, 12. Mean (Standard Deviation). Unit: part per million

Measure	EVP-6124 + NicoDerm CQ (Active) n = 40	EVP-6124 + NRT Patch (Placebo) n = 41	Placebo + NicoDerm CQ (Active) n = 38	Placebo + NRT Patch (Placebo) n = 41
Baseline	20.2 (11)	17.2 (9.8)	20.5 (13.7)	19.3 (9.4)
Week 1	8.6 (11)	9.2 (10.1)	5.2 (6)	8.1 (8.6)
Week 2	7.7 (11.5)	10.1 (10.2)	4.9 (5.4)	8.5 (8.5)
Week 4	6.1 (7.7)	9.8 (11.5)	6.3 (7.9)	9.6 (10.5)
Week 6	7.5 (11.4)	12.7 (16.3)	5.3 (5.7)	7.8 (6.4)
Week 8	7.2 (10.5)	12.6 (16.8)	7.5 (6.4)	7.6 (6.8)
Week 10	7.2 (10.9)	11.2 (11.9)	8.2 (7.4)	5.3 (5)
Week 12	8.8 (8.7)	11.4 (13.6)	9 (8.1)	8.3 (9.3)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: week 1 to week 12. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
EVP-6124 + NicoDerm (Active)	1 of 40 (2.5%)	35 of 40 (87.5%)	Not reported
EVP-6124 + NRT Patch (Placebo)	1 of 41 (2.4%)	30 of 41 (73.2%)	Not reported
Placebo + NicoDerm (Active)	1 of 38 (2.6%)	34 of 38 (89.5%)	Not reported
Placebo + NRT Patch (Placebo)	0 of 41 (0%)	34 of 41 (82.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Nicotine Dependence

Recruiting
Advanced Functional and Structural MRI Techniques for Neuropharmacological Imaging
Drug Abuse, Nicotine Dependence
Not yet recruiting
Quit With Sense: Using Mindful Smoking and Wearable Device for Smoking Cessation
Smoking Cessation, Cigarette Smoking
Recruiting
Adapting and Pilot Testing a Skills-based Smoking Cessation Intervention to Address Developmental and Health-related Stress Among Adults Who Smoke
Smoking Cessation, Depression
Not yet recruitingPhase 2
Effects of Psilocybin on Craving in Nicotine Dependence
Nicotine Dependence
Not yet recruitingObservational study
Prevalence and Association of Dysfunctional Breathing With Nicotine Dependence and Physical Activity Among Young Smokers
Dysfunctional Breathing, Physical Activity

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Anne Eden Evins, MD, MPH principal investigator

Massachusetts General Hospital

Maurizio Fava, MD principal investigator

Massachusetts General Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence (time frame: Week 1, 2, 4, 6, 8, 10, 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01480232.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2017; AzTrials last refreshed its copy on 27 Oct 2026.