Post Anke, Smart Trevor S, Jackson Kimberley, Mann Joanne, Mohs Richard, Rorick-Kehn Linda, Statnick Michael, Anton Raymond, O'Malley Stephanie S, Wong Conrad J
Lilly UK, Windlesham, Surrey, UK.
JStat Services, Ltd, Wokingham, Berkshire, UK.
Alcohol Clin Exp Res. 2016 Sep;40(9):1935-44. doi: 10.1111/acer.13147. Epub 2016 Jul 20.
This was a proof-of-concept study to evaluate the efficacy of LY2940094, a nociceptin/orphanin FQ peptide receptor antagonist, in reducing alcohol consumption in actively alcohol-drinking patients with alcohol dependence.
Eighty-eight patients, 21 to 66 years of age, diagnosed with alcohol dependence, reporting 3 to 6 heavy drinking days per week, were randomized (1:1) to 8 weeks of treatment with once-daily oral placebo (N = 44) or 40 mg/d of LY2940094 (N = 44). The primary efficacy analysis was the change from baseline in number of drinks per day (NDD) utilizing mixed-model repeated measures comparing LY2940094 and placebo in Month 2 of the 8-week double-blind treatment period. The probability that the difference relative to placebo in NDD was ≤0 at endpoint was calculated, and a probability ≥80% was considered to be evidence that LY2940094 was associated with the reduction in NDD.
After 8 weeks of treatment, reduction in mean NDD did not differ between LY2940094 versus placebo (-1.4 vs. -1.5, respectively, 44% probability of greater reduction relative to placebo), but there was a greater reduction in the mean percentage of heavy drinking days in a month with LY2940094 versus placebo (-24.5 vs. -15.7%, respectively, 93% probability of a greater reduction relative to placebo), and an increase in the mean percentage of abstinent days in a month compared to placebo (9.1 vs. 1.9%, respectively, 91% probability of a greater increase relative to placebo). Patients who were treated with LY2940094 showed decreased plasma levels of gamma-glutamyl transferase with probabilities ≥98% for greater reduction compared with placebo at Weeks 1, 4, 6, and 8. Treatment-emergent adverse events in ≥5% of patients treated with LY2940094 included insomnia, vomiting, and anxiety. There were no serious adverse events or significant changes in laboratory assessments or vital signs with LY2940094.
Although not reducing the NDD, LY2940094, compared to placebo, did reduce heavy drinking days and increased abstinence days in patients with alcohol dependence.
这是一项概念验证性研究，旨在评估痛敏肽/孤啡肽FQ肽受体拮抗剂LY2940094在减少酒精依赖的主动饮酒患者酒精摄入量方面的疗效。
88名年龄在21至66岁之间、被诊断为酒精依赖、报告每周有3至6个重度饮酒日的患者被随机（1:1）分为两组，一组接受为期8周的每日一次口服安慰剂治疗（N = 44），另一组接受每日40 mg的LY2940094治疗（N = 44）。主要疗效分析是在8周双盲治疗期的第2个月，利用混合模型重复测量比较LY2940094和安慰剂，计算每日饮酒量（NDD）相对于基线的变化。计算终点时NDD相对于安慰剂的差异≤0的概率，概率≥80%被认为是LY2940094与NDD减少相关的证据。
治疗8周后，LY2940094组与安慰剂组的平均NDD减少量无差异（分别为-1.4和-1.5，相对于安慰剂有更大减少的概率为44%），但与安慰剂相比，LY2940094组一个月内重度饮酒日的平均百分比下降幅度更大（分别为-24.5%和-15.7%，相对于安慰剂有更大减少的概率为93%），且与安慰剂相比，一个月内戒酒日的平均百分比有所增加（分别为9.1%和1.9%，相对于安慰剂有更大增加的概率为91%）。接受LY2940094治疗的患者在第1、4、6和8周时，血浆γ-谷氨酰转移酶水平下降，相对于安慰剂有更大下降的概率≥98%。接受LY2940094治疗的患者中≥5%出现的治疗中出现的不良事件包括失眠、呕吐和焦虑。使用LY2940094未出现严重不良事件，实验室评估或生命体征也无显著变化。
虽然LY2940094没有减少NDD，但与安慰剂相比，它确实减少了酒精依赖患者的重度饮酒日并增加了戒酒日。
