Randomized controlled trial of extended-release buprenorphine vs. sublingual buprenorphine for the treatment opioid use disorder patients using fentanyl analogues

使用芬太尼类似物缓释丁丙诺啡与舌下含服丁丙诺啡治疗阿片类药物使用障碍患者的随机对照试验

• 批准号: 10158460
• 负责人: Frances Rudnick Levin
• 金额: $ 19.89万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10158460
• 关键词: Adverse effects; Analgesics; Automobile Driving; Buprenorphine; Clinical Treatment; Development; Dose; Dropout; Drops; Effectiveness; Epidemic; Fatality rate; Fentanyl; Formulation; Heroin; Holidays; Illicit Drugs; Individual; Injectable; Injection product; Injections; Maintenance; Measures; Methadone; Methods; Morphine; Naltrexone; Nature; New York City; Opioid; Opioid replacement therapy; Outcome; Outcome Measure; Overdose; Patients; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Phase II Clinical Trials; Pilot Projects; Randomized; Randomized Controlled Trials; Relapse; Serious Adverse Event; Serum; Subgroup; Testing; Therapeutic; Time; TimeLine; Toxicology; Treatment Failure; Treatment outcome; U-47700; Urine; Withdrawal Symptom; analog; buprenorphine treatment; carfentanil; craving; effective therapy; experience; improved; mu opioid receptors; non-compliance; open label; opioid epidemic; opioid overdose; opioid use; opioid use disorder; opioid user; opioid withdrawal; overdose death; pill; pilot trial; primary outcome; reduce symptoms; screening; synthetic opioid; trial comparing; Adverse effects; Analgesics; Automobile Driving; Buprenorphine; Clinical Treatment; Development; Dose; Dropout; Drops; Effectiveness; Epidemic; Fatality rate; Fentanyl; Formulation; Heroin; Holidays; Illicit Drugs; Individual; Injectable; Injection product; Injections; Maintenance; Measures; Methadone; Methods; Morphine; Naltrexone; Nature; New York City; Opioid; Opioid replacement therapy; Outcome; Outcome Measure; Overdose; Patients; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Phase II Clinical Trials; Pilot Projects; Randomized; Randomized Controlled Trials; Relapse; Serious Adverse Event; Serum; Subgroup; Testing; Therapeutic; Time; TimeLine; Toxicology; Treatment Failure; Treatment outcome; U-47700; Urine; Withdrawal Symptom; analog; buprenorphine treatment; carfentanil; craving; effective therapy; experience; improved; mu opioid receptors; non-compliance; open label; opioid epidemic; opioid overdose; opioid use; opioid use disorder; opioid user; opioid withdrawal; overdose death; pill; pilot trial; primary outcome; reduce symptoms; screening; synthetic opioid; trial comparing

Project Summary The US opioid epidemic continues to evolve with highly potent synthetic opioids (HPSO) now driving higher overdose fatality rates. There has been a five-fold increase in US synthetic opioid overdose rate from 2013 (3,105) to 2016 (approximately 20,000) out of the approximately 42,000 overdose deaths due to opioids. Fentanyl analogs and other HPSO are now commonly found in heroin and counterfeit prescription painkiller pills. Due to the rapidly changing nature of the illicit drug supply, the efficacy of commonly used pharmacotherapies for opioid use disorder (OUD) (e.g., buprenorphine, methadone, naltrexone) in treating users of HPSO is unknown. The increasing number of overdose deaths combined with possible lower efficacy of standard therapies creates an urgent need to develop new strategies for the HPSO-using patient. Despite the known effectiveness of buprenorphine sublingual (BSL) maintenance treatment, retention and continued non-prescribed opioid use remain significant limitations, with approximately 50% or more of patients treated with BSL dropping out of treatment by 3 to 6 months. The first extended-release injectable buprenorphine (Sublocade™) became commercially available in 2018 after FDA Fast Track and Priority Review designation. This monthly buprenorphine formulation, which is available in two doses (100 mg and 300 mg), can achieve serum buprenorphine concentrations in excess of that achieved by BSL 24 mg per day. Moreover, if an unexpected drug holiday is experienced, at two weeks past the injection due date, µ-opioid receptor remains above 70%, providing extended protection against opioid withdrawal and relapse. While this buprenorphine extended-release (BXR) injection formulation has not yet been compared to BSL treatment, the pharmacologic advantages of an extended-release injection can be expected to improve treatment retention and outcomes. The extended-release injection aspect should improve compliance and reduce relapse by providing more continuous buprenorphine serum levels as compared to the sublingual formulation. We hypothesize that BXR injection will have particular benefit for individuals using fentanyl analogues because by providing continuous therapeutic serum buprenorphine levels there will be substantially less opportunity for non-compliance and relapse. Individuals who discontinue BSL and use HPSO containing opioids may have more difficulty restarting sublingual treatment, leading to treatment failure. We propose an early Phase II clinical trial, in which patients seeking treatment for OUD who are positive for HPSO at screening (N = 40) will be inducted onto BSL and then randomly assigned to receive either standard therapy (BSL maintenance) or BXR injection, under open label conditions, with a primary outcome measure of days of opioid use per week as measured by the timeline followback method confirmed by urine toxicology. To our knowledge, this would be the first trial testing a treatment for individuals with OUD using HPSO.

项目摘要 美国阿片类药物流行病继续进化，现在高度潜在的合成阿片类药物（HPSO）现在推动更高 过量的死亡率。从2013年起，美国合成阿片类药物过量率增加了五倍 （3,105）到2016年（约20,000），在大约42,000人因卵巢毒素导致的过量死亡中。 芬太尼类似物和其他HPSO现在通常在海洛因和伪造处方止痛药中找到 药丸。由于非法药物供应的性质迅速变化，常用的效率 阿片类药物使用障碍的药物疗法（例如，丁丙诺啡，Metagadone，Naltrexone）治疗 HPSO的用户未知。过量死亡人数增加，并可能降低效率 标准疗法迫切需要为使用HPSO的患者制定新的策略。 尽管丁丙诺啡舌下（BSL）维护处理，保留和 持续的非处方阿片类药物使用仍然存在重大局限性，大约50％或更多的患者 用BSL治疗3至6个月的治疗。第一个扩展释放的注射 丁丙诺啡（Sublocade™）在FDA快速轨道和优先级之后，在2018年获得商业上市 评论设计。这个每月的丁丙诺啡配方，有两剂（100毫克和300剂）可用 mg），可以实现血清丁丙诺啡浓度超过每天24 mg BSL所达到的浓度。 此外，如果经历了意外的毒品假期，则在注射到期日之前的两个星期，阿片类药物 接收器保持在70％以上，可扩展防止阿片类药物提取和继电器。同时 丁丙诺啡延长释放（BXR）注射式尚未与BSL治疗， 预期扩展释放注射的药理优势可以改善治疗保留率 和结果。扩展释放的注入方面应提高合规性并减少继电器 与舌下配方相比，提供更连续的丁丙诺啡血清水平。我们 假设BXR注射将对使用芬太尼类似物的个人具有特殊的好处，因为 提供连续的热血清丁丙诺啡水平，将大大减少机会 违规和继电器。停止BSL并使用含有HPSO的阿片类药物的个人可能 更难重新开始舌下治疗，导致治疗失败。 我们提出了一项早期II期临床试验，在该试验中，寻求对OUD治疗的患者呈阳性 筛选时的HPSO（n = 40）将被感应到BSL上，然后随机分配以接收任一标准 在开放标签条件下，治疗（BSL维护）或BXR注射，主要结果指标 按时间线后卫方法测量的每周使用阿片类药物的天数，尿液毒理学证实。到 我们的知识，这将是第一次使用HPSO对OUD患者进行治疗的试验。