Benefit and Safety of Cytisinicline (cytisine) for Cessation of Nicotine E-cigarette Use

金雀花碱（金雀花碱）用于戒断尼古丁电子烟的益处和安全性

• 批准号: 10586834
• 负责人: Cindy Jacobs
• 金额: $ 191.32万
• 依托单位: ACHIEVE LIFE SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10586834
• 关键词: 18 year old; Abstinence; Accountability; Adolescent and Young Adult; Adult; Agonist; Agreement; Behavioral; Binding; Biochemical; Biological Markers; Biological Sciences; Brain; Budgets; Carbon Monoxide; Cardiovascular Diseases; Case Report Form; Characteristics; Cigarette Smoker; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Consent Forms; Contracts; Cotinine; Counseling; Data Collection; Databases; Development; Devices; Dose; Double-Blind Method; Eastern Europe; Electronic Nicotine Delivery Systems; Electronic cigarette; Enrollment; Europe; FDA approved; Health; High Prevalence; Immune system; Individual; Infrastructure; Institutional Review Boards; Intervention; Label; Laboratories; Licensing; Logistics; Lung diseases; Lung infections; Measurement; Measures; Medical; Monitor; Nicotine; Nicotine Dependence; Nicotine Withdrawal; Outcome; Pamphlets; Patient Self-Report; Pharmaceutical Preparations; Pharmacotherapy; Phase; Pilot Projects; Placebo Control; Placebos; Probability; Procedures; Professional Organizations; Program Development; Protocols documentation; Public Health; Pulmonary Inflammation; Questionnaires; Randomized; Relapse; Research Design; Research Personnel; Safety; Safety Management; Saliva; Salivary; Schedule; Severities; Ships; Site; Smoking; Smoking History; Statistical Data Interpretation; Subgroup; System; Testing; Time; Treatment Protocols; Vendor; Visit; Withdrawal Symptom; arm; clinical development; clinical research site; commercialization; compliance behavior; cytisine; data management; demographics; disorder risk; e-cigarette cessation; efficacy evaluation; efficacy outcomes; electronic cigarette use; electronic cigarette user; group intervention; next generation; nicotine cessation; nicotine exposure; nicotine reward; nicotine use; programs; public health priorities; side effect; smoking cessation; smoking relapse; success; treatment duration; treatment effect; uptake; vaper; vaping; vaping nicotine

ABSTRACT Nicotine is highly addictive: >95% of unaided attempts at smoking cessation fail by 6 months. Electronic (e)- cigarettes (vaping) are nicotine-delivery devices that may be useful in some individuals for smoking cessation but are not FDA-approved as a smoking cessation aid and long-term use may have uncertain health impacts. Evidence suggests that vaping nicotine may also raise cardiovascular and pulmonary disease risks. Many experts and professional societies recommend that vapers should also attempt to stop using nicotine e- cigarettes. However, treatments to aid e-cigarette cessation have yet to be identified or FDA-approved. This project will test whether cytisine, a partial nAChR agonist that reduces the severity of nicotine withdrawal symptoms while inhibiting nicotine reward effects in the brain, can promote cessation of e-cigarette use. Prior trials have shown cytisine’s efficacy for smoking cessation, and it has been marketed as a smoking cessation aid in Europe for decades. Achieve Life Sciences has recently (past 3 years) expedited the US clinical development program for cytisine as a smoking cessation aid and now proposes to test for vaping cessation. This will be the first multicenter, randomized, placebo-controlled Pilot study conducted in daily nicotine e- cigarette users to evaluate the benefit and safety of cytisine as a vaping cessation aid. The primary objective is to assess if subjects randomized to 12 weeks of 3 mg cytisine three times a day (TID), vs placebo TID, have a higher prevalence of biochemically- verified nicotine vaping cessation from Week 9 to Week 12. Secondary objectives include assessment of cytisine vs placebo regarding: 1. Earlier vaping cessation initiated at Week 3- 6 or Week 6-9; 2. Vaping reduction, measured by weekly quantitative cotinine levels; 3. Testing moderation effects in efficacy outcomes across subgroups defined by demographic and baseline characteristics. The safety objective will compare the safety profile of cytisine vs placebo when administered for 12 weeks. This study will enroll 150 adult subjects (≥18 years) at 8 US sites, who are daily nicotine e-cigarette users and not current cigarette smokers (confirmed by saliva cotinine and expired carbon monoxide [CO] levels), intending to quit vaping, and willing to set a quit date 7-14 days from the start of study treatment. Subjects will be randomly assigned (2:1) to one of two arms: (cytisine 3 mg TID N=100, or identical placebo TID N=50) for 12 weeks study treatment. All subjects will receive concurrent behavioral support for nicotine/vaping cessation during the study. Study treatment will be double-blind. Vaping status (abstinence) will be assessed by self-report after the planned quit target of 7-14 days post-randomization and assessed weekly from Week 2 through Week 12, including weekly biochemical verification via measurement of salivary cotinine levels. Expired CO levels will be monitored for smoking relapse. Subjects will be assessed for safety during Week 1 of treatment, and weekly thereafter, during the treatment period. Success will be measured as ≥20-30% cessation in the intervention group, and statistically significant (p≤0.1 or 0.05) cytisine benefit in other endpoints.

摘要 尼古丁具有很强的成瘾性：95%的戒烟尝试在6个月内失败。电子(E)- 香烟(电子烟)是一种尼古丁输送装置，对某些人来说可能有助于戒烟。 但不是FDA批准的戒烟辅助剂，长期使用可能会对健康产生不确定的影响。 有证据表明，蒸发尼古丁还可能增加心血管和肺部疾病的风险。许多 专家和专业协会建议，尿布也应该尝试停止使用尼古丁电子烟。 香烟。然而，帮助电子烟戒烟的治疗方法尚未确定或FDA批准。 该项目将测试胞苷，一种部分nAChR激动剂，是否可以降低尼古丁戒断的严重程度 症状虽然抑制了大脑中尼古丁的奖励效应，但可以促进电子烟的停止使用。之前 试验表明，胞二磷胆碱具有戒烟效果，并被作为一种戒烟药物推向市场 在欧洲援助了几十年。实现生命科学最近(过去3年)加速了美国临床 作为戒烟辅助剂的胞二磷胆碱的开发计划，现在建议测试蒸发戒烟。 这将是第一个在每日尼古丁电子烟中进行的多中心、随机、安慰剂对照的试点研究。 评估胞二磷胆碱作为戒烟辅助剂的益处和安全性。主要目标是 为了评估随机服用3毫克一天三次(TID)与安慰剂TID的受试者是否有12周的 从第9周到第12周，经过生物化学验证的尼古丁挥发戒烟的患病率更高。 目标包括评估胞二磷胆碱与安慰剂之间的关系：1.更早的汽化在第3周开始-- 6周或6-9周；2.蒸发减少，以每周定量可替宁水平衡量；3.测试适度 由人口统计学和基线特征定义的亚组对疗效结果的影响。安全 目的比较西替辛与安慰剂在给药12周时的安全性。 这项研究将在美国8个地点招募150名成年受试者(≥18岁)，他们每天都吸尼古丁电子烟， 不是目前的吸烟者(通过唾液可替宁和过期一氧化碳[CO]水平确认)，打算 戒烟，并愿意将戒烟日期定在研究治疗开始后7-14天。受试者将随机 分配(2：1)给两个手臂中的一个：(胞二磷胆碱3 mg，TID N=100，或相同的安慰剂TID N=50)，为期12周的研究 治疗。在研究期间，所有受试者将同时接受尼古丁/汽化戒断的行为支持。 研究治疗将是双盲的。蒸发状态(禁欲)将在计划后通过自我报告进行评估 戒烟目标为随机化后7-14天，从第2周到第12周每周进行评估，包括 每周通过测量唾液可替宁水平进行生化验证。将监控过期的CO水平 为了戒烟。受试者将在治疗的第一周和之后的每周接受安全性评估， 在治疗期间。在干预组中，成功将以≥停止20%-30%来衡量，并且 统计上有意义的(p≤0.1或0.0 5)其他终点的胞二磷胆碱受益。