(#31) Baseline Severity of Illness and Response to Treatment With Aripiprazole Lauroxil Every 2 Months: A Post Hoc Analysis of Phase 3 ALPINE Clinical Trial Data

Abstract: OBJECTIVE: This post hoc analysis examined the efficacy and safety of aripiprazole lauroxil (AL) every-2-months for the treatment of schizophrenia by baseline severity of illness in the double-blind ALPINE study (NCT03345979). METHODS: Adults with acute schizophrenia were randomized to AL 1064 mg every-2-months (initiated with a NanoCrystal Dispersion formulation of AL) or active control (paliperidone palmitate [PP] 156 mg monthly). Based on Clinical Global ImpressionñSeverity scores, baseline severity of illness was categorized as moderate, marked, or severe. Changes from baseline in Positive and Negative Syndrome Scale (PANSS) Total score and PANSS items related to hostility/excitement were assessed at week 25. Numbers of patients with activation adverse events (AEs; anxiety, agitation, and insomnia) were evaluated. RESULTS: Among AL-treated patients, 31/96 (32%) were moderately ill at baseline, 52 (54%) were markedly ill, and 13 (14%) were severely ill (PP: 26/99 [26%], 57 [58%], and 16 [16%], respectively). With AL treatment, mean±SE changes from baseline in PANSS Total score at week 25 were ?21.1±2.5 (moderate; baseline mean, 87.1), ?24.1±1.8 (marked; baseline, 95.3), and ?25.6±6.4 (severe, baseline, 106.1). Improvements from baseline in hostility/excitement-related item scores were similar among severity subgroups. Similar patterns of change in PANSS Total and hostility/excitement-related scores were observed in the PP subgroups. Activation AEs occurred in 7 AL-treated patients (moderate, 3/31 [10%]; marked, 3/52 [6%]; severe 1/13 [8%]; PP: 5/26 [19%], 2/57 [4%], and 3/16 [19%], respectively). CONCLUSIONS: In this post hoc analysis, AL efficacy and safety were comparable across baseline severity-of-illness subgroups of patients with schizophrenia.Short Description: This post hoc analysis of ALPINE evaluated the efficacy and safety of aripiprazole lauroxil (AL) every-2-months by baseline schizophrenia severity (moderate, marked, or severe). Improvements from baseline in Positive and Negative Syndrome Scale (PANSS) Total score and in PANSS hostility/excitement item scores were similar across subgroups at week 25. Baseline severity-of-illness levels were not associated with rates of activation adverse events.Name of Sponsoring Organization(s): This study was sponsored by Alkermes, Inc. Medical writing and editorial support were provided by Peloton Advantage, LLC, an OPEN Health company, and funded by Alkermes, Inc.