Proof-of-Concept Study of EVP-6124, an Alpha-7 Nicotinic Acetylcholine Receptor Agonist, Versus Placebo in Subjects With Nicotine Dependence
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 345
- 试验地点
- 1
- 主要终点
- Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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)
干预措施: EVP-6124 (Drug)
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)
干预措施: NicoDerm Patch (Active) (Drug)
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)
干预措施: Brief Supportive and Behavioral Treatment (Behavioral)
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)
干预措施: Placebo Capsule (Drug)
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)
干预措施: NicoDerm Patch (Active) (Drug)
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)
干预措施: Brief Supportive and Behavioral Treatment (Behavioral)
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)
干预措施: EVP-6124 (Drug)
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)
干预措施: NRT Patch (Placebo) (Drug)
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)
干预措施: Brief Supportive and Behavioral Treatment (Behavioral)
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)
干预措施: Placebo Capsule (Drug)
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)
干预措施: NRT Patch (Placebo) (Drug)
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)
干预措施: Brief Supportive and Behavioral Treatment (Behavioral)
结局指标
主要结局
Effects of EVP-6124 on 7-day Point-prevalence Smoking Abstinence
时间窗: 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
时间窗: Baseline, Weeks 1, 2, 4, 6, 8, 10, 12
CO concentration was measured at every visit.
次要结局
- Effects of EVP-6124 on Cognitive Performance as Measured by the Continuous Performance Test Hit Reaction Time(Baseline, week 1, week 12)
- Safety and Tolerability of EVP-6124 Alone or Combined With NRT(Weeks 1-12)
- Effects of EVP-6124 on Working Memory as Measured by the N-Back Task Reaction Time(Baseline, week 1, week 12)
研究者
A. Eden Evins
Director, Center for Addiction Medicine Massachusetts General Hospital
Massachusetts General Hospital