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

INTRODUCTION: This post-hoc analysis examined the efficacy and safety of aripiprazole lauroxil (AL) by baseline severity of illness in the double-blind ALPINE study (NCT03345979) in patients with schizophrenia treated with AL every 2 months.

METHODS: Adults with acute schizophrenia were randomized to AL 1064mg every 2 months initiated with ALNCD 675mg or active control (paliperidone palmitate [PP] 156mg monthly). Based on CGI-S scores, baseline severity of illness was categorized as moderate, marked, or severe. Changes from baseline in PANSS Total score were assessed at week 25, along with PANSS items related to hostility/excitement. Numbers of patients with activation adverse events (AEs; anxiety, agitation, and insomnia) were also evaluated.

RESULTS: Of 96 AL patients assessed, 31 (32%) were moderately ill at baseline, 52 (54%) were markedly ill, and 13 (14%) were severely ill (PP: moderate, 26/99 [26%]; marked, 57 [58%]; severe, 16 [16%]). With AL treatment, mean±SE changes from baseline in PANSS Total score at week 25 for each subgroup were −21.1±2.5 (moderately ill; baseline, 87.1±5.5), −24.1±1.8 (markedly ill; baseline, 95.3±7.3), and −25.6±6.4 (severely ill, baseline, 106.1±7.2). Improvements from baseline in PANSS scores related to hostility/excitement items were comparable among severity subgroups. Efficacy results for PP subgroups were similar. Activation AEs occurred in 7 AL-treated patients (moderate, 3/31 [10%]; marked, 3/52 [6%]; severe 1/13 [8%]) and 10 PP patients (moderate, 5/26 [19%]; marked, 2/57 [4%]; severe, 3/16 [19%]).

CONCLUSIONS: Regardless of baseline severity of illness, AL efficacy and safety were comparable among patients with schizophrenia in this post hoc analysis.