Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
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DOI：
10.1016/s0140-6736(18)32259-1
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发表时间：
2019-02-23
期刊：
影响因子：
168.9
通讯作者：
Wiest, Katharina L.
中科院分区：
文献类型：
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作者：
Haight, Barbara R.;Learned, Susan M.;Wiest, Katharina L.
RBP-6000，被称为BUP-XR（缓释丁丙诺啡），是一种用于阿片类药物使用障碍的每月皮下注射丁丙诺啡治疗药物。BUP-XR提供持续的丁丙诺啡血浆浓度，以在整个每月给药期间阻断滥用阿片类药物的药物喜好，同时控制戒断和渴望症状。在卫生保健环境中使用BUP-XR还可以减轻滥用、误用、转移和无意暴露。我们的目的是研究不同BUP-XR给药方案对阿片类药物使用障碍患者的疗效。方法：这项随机、双盲、安慰剂对照的3期试验在美国36个治疗中心进行。寻求治疗的18-65岁患有中度或重度阿片类药物使用障碍（根据《精神疾病诊断和统计手册》第五版的定义）的成年人进入了一个开放标签的适应期，用丁丙诺啡-纳洛酮舌下膜治疗长达2周。符合条件的参与者随后被随机分配（4:4:1:1），通过交互式语音/网络响应系统接受BUP-XR 300毫克/300毫克（6次300毫克注射），BUP-XR 300毫克/100毫克（两次300毫克注射加4次100毫克注射），或每28天剂量匹配的安慰剂，并接受每周个人药物咨询。不允许补充丁丙诺啡。主要疗效终点是参与者戒断阿片类药物使用的百分比，定义为从第5周到第24周，每个参与者尿样阴性和自我报告非法阿片类药物使用的百分比，在完整的分析集中进行分析。对所有接受至少一剂BUP-XR或安慰剂的参与者进行安全性评估。本研究已在ClinicalTrials.gov注册，编号NCT02357901。从2015年1月28日至2015年11月12日，筛选了1187名潜在参与者，665人进入磨合期，504人接受了BUP-XR 300 mg/300 mg （n=201）、BUP-XR 300 mg/100 mg （n=203）或安慰剂（n=100）。BUP-XR 300 mg/300 mg组的平均参与者戒断率为41.3% (SD 39.7)， 300 mg/100 mg组为42.7%(38.5)，而安慰剂组为5.0% （17.0）
Background RBP-6000, referred to as BUP-XR (extended-release buprenorphine), is a subcutaneously injected, monthly buprenorphine treatment for opioid use disorder. BUP-XR provides sustained buprenorphine plasma concentrations to block drug-liking of abused opioids over the entire monthly dosing period, while controlling withdrawal and craving symptoms. Administration of BUP-XR in a health-care setting also mitigates abuse, misuse, diversion, and unintentional exposure. We aimed to investigate the efficacy of different BUP-XR dosing regimens in participants with opioid use disorder.Methods This randomised, double-blind, placebo-controlled, phase 3 trial was done at 36 treatment centres in the USA. Treatment-seeking adults aged 18-65 years who had moderate or severe opioid use disorder (as defined by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders) entered an open-label run-in phase of up to 2 weeks' treatment with buprenorphine-naloxone sublingual film. Eligible participants were then randomly assigned (4:4:1:1) with an interactive voice/web-response system to receive BUP-XR 300 mg/300 mg (six injections of 300 mg), BUP-XR 300 mg/100 mg (two injections of 300 mg plus four injections of 100 mg), or volume-matched placebo every 28 days, and received weekly individual drug counselling. No supplemental buprenorphine was allowed. The primary efficacy endpoint was participants' percentage abstinence from opioid use, defined as the percentage of each participant's negative urine samples and self-reports of illicit opioid use from week 5 to week 24, analysed in the full analysis set. Safety was assessed in all participants who received at least one dose of BUP-XR or placebo. This study is registered with ClinicalTrials.gov, number NCT02357901.Findings From Jan 28, 2015, to Nov 12, 2015, 1187 potential participants were screened, 665 entered run-in, and 504 received BUP-XR 300 mg/300 mg (n=201), BUP-XR 300 mg/100 mg (n=203), or placebo (n=100). Mean participants' percentage abstinence was 41.3% (SD 39.7) for BUP-XR 300 mg/300 mg and 42.7% (38.5) for 300 mg/100 mg, compared with 5.0% (17.0) for placebo (p