Nicotine Dependence, Smoking Cessation
Conditions
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
Interventions
DRUGEVP-6124
One EVP-6124 capsule ingested orally daily for 12 weeks (84 days)
DRUGPlacebo Capsule
One placebo capsule ingested orally daily for 12 weeks (84 days)
DRUGNicoDerm 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).
DRUGNRT Patch (Placebo)
One NRT patch (Placebo) daily for first 6 weeks (42 days).
BEHAVIORALBrief 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.
Sponsors
FORUM Pharmaceuticals Inc
National Institute on Drug Abuse (NIDA)
A. Eden Evins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | 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 | Baseline, Weeks 1, 2, 4, 6, 8, 10, 12 | CO concentration was measured at every visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | 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 | 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 | 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) |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited using advertisements in the local media market.Those who made contact in response to advertisements spoke initially with a research coordinator who provided further information about the study, answered initial questions from the potential subject, and administered a 10-minute questionnaire assessing eligibility.
Pre-assignment details
Prior to initiation of any study procedures, the informed consent process was conducted by a study physician who explained the study in detail making sure that the subject understood the potential risks/benefits as outlined in the consent form; 350 signed consent, 60 were found ineligible and 130 either withdrew consent or was discontinued
Participants by arm
| Arm | Count |
|---|---|
| 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)
EVP-6124: One EVP-6124 capsule ingested orally daily for 12 weeks (84 days)
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).
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. | 40 |
| 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)
EVP-6124: One EVP-6124 capsule ingested orally daily for 12 weeks (84 days)
NRT Patch (Placebo): One NRT patch (Placebo) daily for first 6 weeks (42 days).
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. | 41 |
| 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)
Placebo Capsule: One placebo capsule ingested orally daily for 12 weeks (84 days)
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).
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. | 38 |
| 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)
Placebo Capsule: One placebo capsule ingested orally daily for 12 weeks (84 days)
NRT Patch (Placebo): One NRT patch (Placebo) daily for first 6 weeks (42 days).
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. | 41 |
| Total | 160 |
Baseline characteristics
| Characteristic | EVP-6124 + NicoDerm (Active) | EVP-6124 + NRT Patch (Placebo) | Placebo + NicoDerm (Active) | Placebo + NRT Patch (Placebo) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 42.63 years STANDARD_DEVIATION 12.17 | 44.70 years STANDARD_DEVIATION 13.06 | 44.03 years STANDARD_DEVIATION 12.81 | 45.15 years STANDARD_DEVIATION 11.42 | 44.30 years STANDARD_DEVIATION 11.86 |
| Cigarettes Smoked Per Day | 18.53 cigarettes per day STANDARD_DEVIATION 9.35 | 19.41 cigarettes per day STANDARD_DEVIATION 15.09 | 22.87 cigarettes per day STANDARD_DEVIATION 30.63 | 20.04 cigarettes per day STANDARD_DEVIATION 13.85 | 20.21 cigarettes per day STANDARD_DEVIATION 17.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 4 Participants | 3 Participants | 1 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 37 Participants | 35 Participants | 40 Participants | 144 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Expired CO, ppm | 5.18 parts per million STANDARD_DEVIATION 4.17 | 4.29 parts per million STANDARD_DEVIATION 2.76 | 4.78 parts per million STANDARD_DEVIATION 3.46 | 4.85 parts per million STANDARD_DEVIATION 4.38 | 4.78 parts per million STANDARD_DEVIATION 3.69 |
| FTND Score | 5.40 units on a scale STANDARD_DEVIATION 2.07 | 5.34 units on a scale STANDARD_DEVIATION 2.17 | 5.39 units on a scale STANDARD_DEVIATION 1.94 | 5.32 units on a scale STANDARD_DEVIATION 2.07 | 5.36 units on a scale STANDARD_DEVIATION 2.06 |
| Race/Ethnicity, Customized African American | 8 Participants | 3 Participants | 7 Participants | 10 Participants | 28 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 30 Participants | 36 Participants | 29 Participants | 30 Participants | 125 Participants |
| Sex: Female, Male Female | 14 Participants | 14 Participants | 13 Participants | 17 Participants | 58 Participants |
| Sex: Female, Male Male | 26 Participants | 27 Participants | 25 Participants | 24 Participants | 102 Participants |
| Years of Regular Smoking | 23.31 years STANDARD_DEVIATION 11.01 | 26.38 years STANDARD_DEVIATION 13.24 | 24.89 years STANDARD_DEVIATION 12.84 | 26.46 years STANDARD_DEVIATION 12.17 | 25.26 years STANDARD_DEVIATION 12.32 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 35 / 40 | 30 / 41 | 34 / 38 | 34 / 41 |
| serious Total, serious adverse events | 1 / 40 | 1 / 41 | 1 / 38 | 0 / 41 |
Outcome results
Primary
Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point
CO concentration was measured at every visit.
Time frame: Baseline, Weeks 1, 2, 4, 6, 8, 10, 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EVP-6124 + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Baseline | 20.2 part per million | Standard Deviation 11 |
| EVP-6124 + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 1 | 8.6 part per million | Standard Deviation 11 |
| EVP-6124 + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 2 | 7.7 part per million | Standard Deviation 11.5 |
| EVP-6124 + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 4 | 6.1 part per million | Standard Deviation 7.7 |
| EVP-6124 + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 6 | 7.5 part per million | Standard Deviation 11.4 |
| EVP-6124 + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 8 | 7.2 part per million | Standard Deviation 10.5 |
| EVP-6124 + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 10 | 7.2 part per million | Standard Deviation 10.9 |
| EVP-6124 + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 12 | 8.8 part per million | Standard Deviation 8.7 |
| EVP-6124 + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 8 | 12.6 part per million | Standard Deviation 16.8 |
| EVP-6124 + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 6 | 12.7 part per million | Standard Deviation 16.3 |
| EVP-6124 + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 1 | 9.2 part per million | Standard Deviation 10.1 |
| EVP-6124 + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 12 | 11.4 part per million | Standard Deviation 13.6 |
| EVP-6124 + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 10 | 11.2 part per million | Standard Deviation 11.9 |
| EVP-6124 + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 4 | 9.8 part per million | Standard Deviation 11.5 |
| EVP-6124 + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 2 | 10.1 part per million | Standard Deviation 10.2 |
| EVP-6124 + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Baseline | 17.2 part per million | Standard Deviation 9.8 |
| Placebo + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 10 | 8.2 part per million | Standard Deviation 7.4 |
| Placebo + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 2 | 4.9 part per million | Standard Deviation 5.4 |
| Placebo + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 4 | 6.3 part per million | Standard Deviation 7.9 |
| Placebo + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 6 | 5.3 part per million | Standard Deviation 5.7 |
| Placebo + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 8 | 7.5 part per million | Standard Deviation 6.4 |
| Placebo + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 12 | 9 part per million | Standard Deviation 8.1 |
| Placebo + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Baseline | 20.5 part per million | Standard Deviation 13.7 |
| Placebo + NicoDerm CQ (Active) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 1 | 5.2 part per million | Standard Deviation 6 |
| Placebo + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 2 | 8.5 part per million | Standard Deviation 8.5 |
| Placebo + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 4 | 9.6 part per million | Standard Deviation 10.5 |
| Placebo + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 1 | 8.1 part per million | Standard Deviation 8.6 |
| Placebo + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Baseline | 19.3 part per million | Standard Deviation 9.4 |
| Placebo + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 6 | 7.8 part per million | Standard Deviation 6.4 |
| Placebo + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 12 | 8.3 part per million | Standard Deviation 9.3 |
| Placebo + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 10 | 5.3 part per million | Standard Deviation 5 |
| Placebo + NRT Patch (Placebo) | Difference in Expired Carbon Monoxide (CO) Concentration From Baseline to End Point | Week 8 | 7.6 part per million | Standard Deviation 6.8 |
Primary
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.
Time frame: Week 1, 2, 4, 6, 8, 10, 12
Population: The primary smoking cessation variable is biochemically verified self-report of 7-day point prevalence abstinence at 12 weeks (end of treatment).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 1 | 25.0 % participants with 7-Day Point Prevalen |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 10 | 37.5 % participants with 7-Day Point Prevalen |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 8 | 37.5 % participants with 7-Day Point Prevalen |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 2 | 47.5 % participants with 7-Day Point Prevalen |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 12 | 25.0 % participants with 7-Day Point Prevalen |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 4 | 40.0 % participants with 7-Day Point Prevalen |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 6 | 52.5 % participants with 7-Day Point Prevalen |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 10 | 12.2 % participants with 7-Day Point Prevalen |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 6 | 14.6 % participants with 7-Day Point Prevalen |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 4 | 17.1 % participants with 7-Day Point Prevalen |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 8 | 14.6 % participants with 7-Day Point Prevalen |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 12 | 12.2 % participants with 7-Day Point Prevalen |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 2 | 19.5 % participants with 7-Day Point Prevalen |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 1 | 12.2 % participants with 7-Day Point Prevalen |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 6 | 34.2 % participants with 7-Day Point Prevalen |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 1 | 28.9 % participants with 7-Day Point Prevalen |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 2 | 42.1 % participants with 7-Day Point Prevalen |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 4 | 44.7 % participants with 7-Day Point Prevalen |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 8 | 28.9 % participants with 7-Day Point Prevalen |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 10 | 23.7 % participants with 7-Day Point Prevalen |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 12 | 18.4 % participants with 7-Day Point Prevalen |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 4 | 19.5 % participants with 7-Day Point Prevalen |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 12 | 19.5 % participants with 7-Day Point Prevalen |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 10 | 24.4 % participants with 7-Day Point Prevalen |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 2 | 24.4 % participants with 7-Day Point Prevalen |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 1 | 17.1 % participants with 7-Day Point Prevalen |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 8 | 24.4 % participants with 7-Day Point Prevalen |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence | Seven-Day Point Prevalence Abstinence Rate week 6 | 22.0 % participants with 7-Day Point Prevalen |
Secondary
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.
Time frame: Baseline, week 1, week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | Baseline Hit RT | 436.26 mili seconds | Standard Deviation 78.15 |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | Week 12 Hit RT | 441.73 mili seconds | Standard Deviation 71.59 |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | Week 1 Hit RT | 424.77 mili seconds | Standard Deviation 76.85 |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | Week 1 Hit RT | 429.99 mili seconds | Standard Deviation 59.94 |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | Baseline Hit RT | 434.72 mili seconds | Standard Deviation 65.4 |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | Week 12 Hit RT | 421.66 mili seconds | Standard Deviation 67.67 |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | Baseline Hit RT | 427.76 mili seconds | Standard Deviation 66.87 |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | Week 12 Hit RT | 432.56 mili seconds | Standard Deviation 73.91 |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | Week 1 Hit RT | 418.74 mili seconds | Standard Deviation 60.32 |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | Week 1 Hit RT | 407.97 mili seconds | Standard Deviation 68.01 |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | Baseline Hit RT | 423.94 mili seconds | Standard Deviation 72.58 |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time | Week 12 Hit RT | 396.78 mili seconds | Standard Deviation 53.44 |
Secondary
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)
Time frame: Baseline, week 1, week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Baseline 2-Back RT | 634.04 mili seconds | Standard Deviation 166.51 |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Baseline 3-Back RT | 667.75 mili seconds | Standard Deviation 202.35 |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 1 2-Back RT | 578.58 mili seconds | Standard Deviation 101.86 |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 1 3-Back RT | 635.08 mili seconds | Standard Deviation 164.16 |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 12 2-Back RT | 608.03 mili seconds | Standard Deviation 145.92 |
| EVP-6124 + NicoDerm CQ (Active) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 12 3-Back RT | 639.51 mili seconds | Standard Deviation 175.91 |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 12 2-Back RT | 620.28 mili seconds | Standard Deviation 175.61 |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Baseline 2-Back RT | 645.01 mili seconds | Standard Deviation 180.83 |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 1 3-Back RT | 627.85 mili seconds | Standard Deviation 180.06 |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 1 2-Back RT | 619.42 mili seconds | Standard Deviation 174.86 |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Baseline 3-Back RT | 642.89 mili seconds | Standard Deviation 182.2 |
| EVP-6124 + NRT Patch (Placebo) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 12 3-Back RT | 613.75 mili seconds | Standard Deviation 176.4 |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 12 2-Back RT | 598.47 mili seconds | Standard Deviation 156.28 |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 1 2-Back RT | 565.84 mili seconds | Standard Deviation 148.24 |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 12 3-Back RT | 611.85 mili seconds | Standard Deviation 185.75 |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Baseline 3-Back RT | 620.55 mili seconds | Standard Deviation 210.04 |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 1 3-Back RT | 608.94 mili seconds | Standard Deviation 152.38 |
| Placebo + NicoDerm CQ (Active) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Baseline 2-Back RT | 632.80 mili seconds | Standard Deviation 176.78 |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 1 3-Back RT | 586.15 mili seconds | Standard Deviation 173.28 |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 12 3-Back RT | 585.15 mili seconds | Standard Deviation 177.86 |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Baseline 3-Back RT | 600.78 mili seconds | Standard Deviation 179.64 |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Baseline 2-Back RT | 616.33 mili seconds | Standard Deviation 186.83 |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 1 2-Back RT | 553.90 mili seconds | Standard Deviation 135 |
| Placebo + NRT Patch (Placebo) | Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time | Week 12 2-Back RT | 565.41 mili seconds | Standard Deviation 149.08 |
Secondary
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
Time frame: Weeks 1-12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EVP-6124 + NicoDerm CQ (Active) | Safety and Tolerability of EVP-6124 Alone or Combined With NRT | 35 Participants |
| EVP-6124 + NRT Patch (Placebo) | Safety and Tolerability of EVP-6124 Alone or Combined With NRT | 30 Participants |
| Placebo + NicoDerm CQ (Active) | Safety and Tolerability of EVP-6124 Alone or Combined With NRT | 34 Participants |
| Placebo + NRT Patch (Placebo) | Safety and Tolerability of EVP-6124 Alone or Combined With NRT | 34 Participants |