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

Smoking Cessation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01480232
• Other study ID #: EVP-6124-014
• Secondary ID: 1R01DA030992-01
• Status: Terminated
• Phase: Phase 2
• First received: November 23, 2011
• Last updated: July 20, 2016
• Start date: December 2011
• Est. completion date: September 2015

Study information

• Verified date: July 2016
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 345
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 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 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Nicotine Dependence
• Smoking Cessation
• Tobacco Use Disorder

Intervention

Drug:
• EVP-6124
One EVP-6124 capsule ingested orally daily for 12 weeks (84 days)
• Placebo Capsule
One placebo capsule ingested orally daily for 12 weeks (84 days)
• 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).
• 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.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
A. Eden Evins	FORUM Pharmaceuticals Inc, National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Weeks 1-12	No
Primary	Difference in expired CO concentration	CO concentration over time will be plotted to determine whether there is variation in the effect of EVP-6124, using a random effect model.	Weeks 1-12	No
Secondary	Effects of EVP-6124 on cognitive performance	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).	Weeks 1-12	No
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.	Weeks 1-14	Yes