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: 10630247
• 负责人: Cindy Jacobs
• 金额: $ 58.47万
• 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/10630247
• 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; Cigarette Smoker; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Consent Forms; Contracts; Cotinine; Counseling; Data Collection; Databases; Development; Devices; Dose; Double-Blind Method; Drug Packaging; Eastern Europe; Electronic Nicotine Delivery Systems; Electronic cigarette; Electronics; Enrollment; Europe; FDA approved; Health; High Prevalence; Immune system; Individual; Infrastructure; Institutional Review Boards; Intervention; Label; Laboratories; Licensing; Logistics; Lung diseases; Lung infections; Marketing; Measurement; Measures; Medical; Monitor; Natural Compound; 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; Qualifying; Questionnaires; Randomized; Recommendation; Relapse; Research Design; Research Personnel; Safety; Safety Management; Saliva; Salivary; Schedule; Self Assessment; Severities; Site; Smoking; Smoking History; Statistical Data Interpretation; Subgroup; System; Testing; Treatment Protocols; Vendor; Visit; Withdrawal Symptom; arm; cigarette user; clinical development; clinical research site; commercialization; comparison control; 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; safety assessment; 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.

抽象的 尼古丁是高度添加剂的：> 95％的无助戒烟尝试失败了6个月。电子（E） - 民事（VAPING）是尼古丁交通设备，对于某些人来说，可能对戒烟有用 但是，由于戒烟援助和长期使用可能会产生不确定的健康影响，因此并未被FDA批准。 有证据表明，烟雾蛋白也可能增加心血管和肺部疾病风险。许多 专家和专业社会建议，Vapers还应试图停止使用Nicotine E- 香烟。但是，尚未确定或批准FDA的治疗方法。 该项目将测试Cytisine是否是降低尼古丁戒断严重程度的部分NACHR激动剂 症状在抑制大脑中的尼古丁奖励效果的同时，可以促进使用电子烟的使用。事先的 试验表明，辛茶的效率在戒烟方面的效率，并被销售为戒烟 数十年来在欧洲援助。实现生命科学最近（过去3年）加快了美国临床 氰氨酸的开发计划是一种戒烟援助，现在提出了测试戒烟的建议。 这将是第一个在每日尼古丁E-进行的多中心，随机，安慰剂对照的试点研究 卷烟使用者评估氰胺作为戒烟辅助的好处和安全性。主要目的是 评估受试者是否每天3次随机分别为3 mg cytisine（TID），vs安慰剂TID 从第9周到第12周，生化验证的尼古丁烟雾戒烟的较高患病率。 目的包括对：1。在第3周开始启动的cytisine vs安慰剂的评估。 6或6-9周； 2。减少烟雾，通过每周定量可替宁水平衡量； 3。测试适中 由人口统计学和基线特征定义的亚组的效率结果的影响。安全 目标将比较甘氨酸与安慰剂的安全概况12周。 这项研究将在美国8个网站上注册150名成人受试者（≥18岁），每天都是Nicotine E-E-a-abigarette用户和 不是目前的吸烟者（由唾液可替宁和过期的一氧化碳[CO]水平确认） 戒烟，并愿意从学习治疗开始后7-14天放弃日期。受试者将是随机的 分配（2：1）到两个臂之一：（ cytisine 3 mg tid n = 100，或相同的安慰剂tid n = 50）在12周 治疗。在研究期间，所有受试者都将获得尼古丁/烟雾戒烟的同时行为支持。 学习治疗将是双盲。烟雾状态（禁欲）将在计划之后通过自我报告进行评估 随机化后7-14天退出目标，从第2周到第12周进行每周评估，包括 每周通过测量唾液可替宁水平的生化验证。过期的CO级别将受到监控 用于吸烟接力。在治疗的第1周以及此后每周的第1周，将对受试者进行安全性评估。 在治疗期间。在干预组中，成功将被衡量为≥20-30％的停止，并且 在其他终点中，统计学意义（p≤0.1或0.05）细胞蛋白益处。