Effects of the Opioid System Modulator, Samidorphan, on Measures of Alcohol Consumption and Patient-Reported Outcomes in Adults with Alcohol Dependence.

IF 3.2 3区 医学 Q1 Medicine Alcoholism, clinical and experimental research Pub Date : 2018-10-01 Epub Date: 2018-08-13 DOI:10.1111/acer.13849
Stephanie S O'Malley, Mark S Todtenkopf, Yangchun Du, Elliot Ehrich, Bernard L Silverman
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引用次数: 12

Abstract

Background: Demonstrating clinically meaningful benefits of alcohol use disorder treatments is challenging.

Methods: We report findings from a 12-week, phase 2, randomized, double-blind, placebo-controlled study of samidorphan (1, 2.5, or 10 mg/d) in adults with alcohol use disorder (NCT00981617). The primary end point was percentage of subjects with no heavy drinking days (PSNHDD) during weeks 5 to 12; secondary end points included alcohol consumption measures, craving, and patient-rated outcomes.

Results: Altogether, 406 patients were included in the full analysis set (101, 104, 100, and 101 in the placebo, samidorphan 1, 2.5, and 10 mg treatment groups, respectively). There was no statistical difference between samidorphan and placebo groups on PSNHDD during weeks 5 to 12. However, dose-dependent reductions in cumulative rate of heavy drinking days were observed (-41%, p < 0.001 for samidorphan 10 mg/d vs. placebo; -30 and -32% for samidorphan 2.5 and 1 mg, p < 0.05 for both). A higher percentage of samidorphan- than placebo-treated patients had a ≥2-category downshift in World Health Organization (WHO) risk levels of drinking. There were significant reductions from baseline with samidorphan versus placebo in alcohol craving (for samidorphan 10 mg: -38.2 [standard error: 2.9] vs. placebo: -30.2 [2.8]; p = 0.044). On a Patient Global Assessment of Response to Therapy (PGART), samidorphan 10 mg was superior to placebo at 4, 8, and 12 weeks (p < 0.001, p < 0.001, p < 0.01, respectively). Improvement in PGART correlated with a reduction in craving and a decrease in WHO risk level.

Conclusions: Results for the primary outcome measure PSNHDD were negative, but at variance with other measures and patient treatment perceptions that may be relevant for interventional studies. These findings highlight the importance of understanding the most relevant outcomes to patients and incorporating and prioritizing patient-centered outcomes when assessing interventions for alcohol use disorder.

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阿片系统调节剂Samidorphan对酒精依赖成人酒精消耗和患者报告结果的影响
背景:证明酒精使用障碍治疗的临床有意义的益处是具有挑战性的。方法:我们报告了一项为期12周的2期随机、双盲、安慰剂对照研究的结果,该研究使用samidorphan(1、2.5或10 mg/d)治疗酒精使用障碍成人(NCT00981617)。主要终点是第5至12周无重度饮酒天数(PSNHDD)的受试者百分比;次要终点包括酒精消耗测量、渴望和患者评价的结果。结果:总共有406例患者被纳入完整分析集(安慰剂、samidorphan 1、2.5和10mg治疗组分别为101例、104例、100例和101例)。在第5至12周,samidorphan组和安慰剂组在PSNHDD治疗上没有统计学差异。然而,观察到重度饮酒天数累积率的剂量依赖性降低(-41%,p)。结论:主要结局指标PSNHDD的结果为阴性,但与可能与干预性研究相关的其他指标和患者对治疗的看法存在差异。这些发现强调了在评估酒精使用障碍干预措施时,了解与患者最相关的结果以及纳入和优先考虑以患者为中心的结果的重要性。
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来源期刊
CiteScore
5.90
自引率
9.40%
发文量
219
审稿时长
1 months
期刊介绍: Alcoholism: Clinical and Experimental Research''s scope spans animal and human clinical research, epidemiological, experimental, policy, and historical research relating to any aspect of alcohol abuse, dependence, or alcoholism. This journal uses a multi-disciplinary approach in its scope of alcoholism, its causes, clinical and animal effect, consequences, patterns, treatments and recovery, predictors and prevention.
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