Leslie Citrome1,2,3,4, Stephanie S O'Malley1,2,3,4, David McDonnell1,2,3,4, Ying Jiang1,2,3,4, Adam C Simmons1,2,3,4, Mark P Berry1,2,3,4, Lauren E Dipetrillo1,2,3,4. 1. Dr. Citrome is with the Department of Psychiatry and Behavioral Sciences at New York Medical College in Valhalla, New York. 2. Dr. O'Malley is with the Department of Psychiatry at the Yale School of Medicine in New Haven, Connecticut. 3. Dr. McDonnell is with Alkermes Pharma Ireland Limited in Roscommon, Ireland. 4. Drs. Jiang, Simmons, Berry, and DiPetrillo are with Alkermes, Inc. in Waltham, Massachusetts.
Abstract
Background: 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. Methods: We describe the design of a Phase II, double-blind, randomized trial to evaluate adult outpatients with schizophrenia and comorbid AUD receiving a combination ofolanzapine 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. Discussion: 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. Trial registration: Clinical trials NCT02161718, registered May 2014; EudraCT Number: 2014-001211-39.
RCT Entities:
Background: 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. Methods: 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. Discussion: 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. Trial registration: Clinical trials NCT02161718, registered May 2014; EudraCT Number: 2014-001211-39.
Entities:
Keywords:
ALKS 3831; Schizophrenia; alcohol use disorder; olanzapine; samidorphan
Authors: Douglas M Ziedonis; David Smelson; Richard N Rosenthal; Steven L Batki; Alan I Green; Renata J Henry; Ivan Montoya; Joseph Parks; Roger D Weiss Journal: J Psychiatr Pract Date: 2005-09 Impact factor: 1.325
Authors: Ismene L Petrakis; Stephanie O'Malley; Bruce Rounsaville; James Poling; Colette McHugh-Strong; John H Krystal Journal: Psychopharmacology (Berl) Date: 2003-11-21 Impact factor: 4.530
Authors: Steven L Batki; Jacqueline A Dimmock; Michael Wade; Paul W Gately; Martha Cornell; Stephen A Maisto; Kate B Carey; Robert Ploutz-Snyder Journal: Am J Addict Date: 2007 Jul-Aug