Citrome Leslie, O'Malley Stephanie S, McDonnell David, Jiang Ying, Simmons Adam C, Berry Mark P, Dipetrillo Lauren E
Dr. Citrome is with the Department of Psychiatry and Behavioral Sciences at New York Medical College in Valhalla, New York.
Dr. O'Malley is with the Department of Psychiatry at the Yale School of Medicine in New Haven, Connecticut.
Innov Clin Neurosci. 2019 May 1;16(5-6):15-21.
Alcohol use disorder (AUD) is a common comorbidity in patients with schizophrenia. Although pharmacological options for the management of each disease exist separately, there is no agent approved for both. Moreover, studies conducted in this patient population, who face practical and social challenges as a consequence of being diagnosed with schizophrenia and comorbid AUD, are limited. We describe the design of a Phase II, double-blind, randomized trial to evaluate adult outpatients with schizophrenia and comorbid AUD receiving a combination of olanzapine plus samidorphan (OLZ+SAM; ALKS 3831), a novel entity currently under development for the treatment of schizophrenia. The combination drug formulation of OLZ+SAM is intended to provide the antipsychotic efficacy of OLZ while mitigating the weight gain and concomitant metabolic abnormalities commonly associated with OLZ alone. In considering this patient population, the novel primary efficacy endpoint is the time from randomization to the first event of exacerbation of disease symptoms (EEDS) based on the occurrence of any of eight prespecified events related to worsening of disease symptoms and/or AUD, as confirmed by a blinded independent adjudication committee. The rate and number of EEDS, improvement in drinking level, and the safety and tolerability of OLZ in combination with SAM will also be assessed. A limited number of studies have been conducted in patients with schizophrenia and AUD, and the need for further research in this difficult-to-study population is well documented. This study is, to our knowledge, the largest and longest trial with a randomized, double-blind, active-controlled design. In addition to providing evidence for the development of OLZ+SAM (ALKS 3831) as a therapeutic option, the study aims to provide insights into the clinical management of subjects with schizophrenia and comorbid AUD. Clinical trials NCT02161718, registered May 2014; EudraCT Number: 2014-001211-39.
酒精使用障碍（AUD）是精神分裂症患者中常见的共病情况。虽然分别存在针对每种疾病的药物治疗选择，但尚无获批用于两者的药物。此外，针对这一因被诊断患有精神分裂症和共病AUD而面临实际和社会挑战的患者群体所开展的研究有限。我们描述了一项II期双盲随机试验的设计，以评估成年精神分裂症合并AUD门诊患者接受奥氮平加沙米朵芬（OLZ+SAM；ALKS 3831）联合治疗的效果，ALKS 3831是一种目前正在研发用于治疗精神分裂症的新药物。OLZ+SAM的联合药物制剂旨在提供奥氮平的抗精神病疗效，同时减轻通常单独使用奥氮平所伴随的体重增加和代谢异常。考虑到这一患者群体，新的主要疗效终点是基于与疾病症状和/或AUD恶化相关的八个预先指定事件中的任何一个发生情况，从随机分组到疾病症状首次加重事件（EEDS）的时间，该时间由一个盲法独立判定委员会确认。还将评估EEDS的发生率和数量、饮酒水平的改善情况以及OLZ与SAM联合使用的安全性和耐受性。针对精神分裂症和AUD患者开展的研究数量有限，对这一难以研究的人群进行进一步研究的必要性已有充分记录。据我们所知，本研究是规模最大、时间最长的采用随机双盲、活性对照设计的试验。除了为将OLZ+SAM（ALKS 3831）开发为一种治疗选择提供证据外，该研究旨在深入了解精神分裂症合并AUD患者的临床管理。临床试验编号NCT02161718，于2014年5月注册；欧盟临床试验编号：2014-001211-39。
