M19. Social and Functional Outcomes: Results: From a 12-Week Phase 3 Study of 2 Doses Aripiprazole Lauroxil vs Placebo: A Post Hoc Analysis

Abstract

Background: Social functioning impairments, a hallmark of schizophrenia, are relatively unresponsive to pharmacologic interventions. Aripiprazole lauroxil (AL; ARISTADA, Alkermes, Inc.) is a long-acting injectable anti-psychotic approved for the treatment of schizophrenia. We examined the degree to which therapeutic doses of AL might reduce social and functional impairments compared to placebo (PBO) in patients with acute schizophrenia during 12 weeks of treatment [1]. Interest in this area has progressed from early work of creating a Positive and Negative Syndrome Scale (PANSS) subscale (G16 [active social avoidance], N2 [emotional with-drawal], N4 [passive social withdrawal], N7 [stereotyped thinking], P3 [hallucinatory behavior], P6 [suspiciousness/persecution]) to measure prosocial behavior, which was then modifed further to a 4-item subscale (items G16, N2, N4, and N5 [diffculty in abstract thinking]) [2]. The PANSS Prosocial subscale was the predecessor to the Personal and Social Performance Scale (PSP) that is now the gold standard for this domain. Methods: Patients with acute schizophrenia (n = 623) in a double-blind, placebo-controlled trial were randomized in a 1:1:1 ratio to receive AL 441 mg, AL 882 mg, or matching PBO once monthly for 12 weeks. Social functioning was measured with the PANSS Prosocial and modifed PANSS Prosocial subscales and PSP total. In a post hoc analysis, we assessed the PSP total score to evaluate a composite measure and analyzed the 6-and 4-item PANSS subscales using analysis of covariance with last observation carried forward for imputation of missing data. Results: There was a signifcant improvement in the 6-item and 4-item PANSS Prosocial scores with AL treatment (both 441 mg and 882 mg) compared to PBO (observed Day 8 to Week 12 [all P 10 points at all time points (deemed a clinically meaningful change [3]). Limitations of this study include its short duration, the use of subscales, and post hoc nature. This study was funded by Alkermes, Inc.