阿立哌唑月制剂 1 日起始用于急性精神分裂症住院患者门诊治疗转换的疗效和安全性：第 3 阶段、随机、双盲、阳性对照 ALPINE 研究。

Efficacy and Safety of a 2-Month Formulation of Aripiprazole Lauroxil With 1-Day Initiation in Patients Hospitalized for Acute Schizophrenia Transitioned to Outpatient Care: Phase 3, Randomized, Double-Blind, Active-Control ALPINE Study.

机构信息

Karuna Therapeutics, 33 Arch Street, Suite 3110, Boston, MA 02110.

Alkermes, Inc, Waltham, Massachusetts, USA.

出版信息

J Clin Psychiatry. 2020 May 19;81(3):19m13207. doi: 10.4088/JCP.19m13207.

DOI:10.4088/JCP.19m13207

PMID:32433835

Abstract

OBJECTIVE

Evaluate efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) with 1-day initiation during hospitalization for acute exacerbation of schizophrenia followed by transition to outpatient care.

METHODS

The phase 3b double-blind Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness (ALPINE) study was conducted from November 2017 to March 2019. Adults with acute schizophrenia according to DSM-5 criteria were randomized (1:1) to AL (AL NanoCrystal Dispersion + oral aripiprazole 30 mg, day 1; AL 1,064 mg, day 8 and every 8 weeks [q8wk]) or paliperidone palmitate (PP 234 mg, day 1; PP 156 mg, day 8 and then q4wk) for 25 weeks. Patients remained hospitalized ≥ 2 weeks after randomization per protocol. Primary endpoint was within-group change in Positive and Negative Syndrome Scale total score (PANSST) from baseline to week 4. Secondary analyses included within- and between-group changes from baseline at various time points. Adverse events (AEs) and laboratory data were monitored.

RESULTS

A total of 200 patients were randomized (AL, n = 99; PP, n = 101); 56.6% and 42.6%, respectively, completed the study. For AL, the mean baseline PANSST was 94.1; scores were significantly reduced from baseline at week 4 (-17.4; P < .001) and were also reduced at weeks 9 (-19.8) and 25 (-23.3). With PP, PANSST also improved significantly from baseline (94.6) at week 4 (-20.1; P < .001) and also improved at weeks 9 (-22.5) and 25 (-21.7). The 3 most common AEs over 25 weeks in the AL group were injection site pain (17.2%), increased weight (9.1%), and akathisia (9.1%). The same AEs were the most common in the PP group (injection site pain [24.8%], increased weight [16.8%], and akathisia [10.9%]).

CONCLUSIONS

AL and PP were efficacious and well-tolerated for initiating treatment of schizophrenia in the hospital and continuing outpatient treatment.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT03345979.

摘要

目的

评估阿立哌唑月桂酰酯（AL）2 个月疗程在住院治疗精神分裂症急性加重期的疗效和安全性，第 1 天采用 1 天起始治疗，随后过渡至门诊治疗。

方法

这是一项为期 3b 期、双盲、阿立哌唑月桂酰酯和棕榈酸帕利哌酮：起始有效性（ALPINE）研究，于 2017 年 11 月至 2019 年 3 月进行。根据 DSM-5 标准诊断为急性精神分裂症的成年患者按 1:1 比例随机（AL NanoCrystal Dispersion+口服阿立哌唑 30mg，第 1 天；AL 1064mg，第 8 天，每 8 周[q8wk]）或棕榈酸帕利哌酮（PP 234mg，第 1 天；PP 156mg，第 8 天，然后 q4wk）治疗 25 周。根据方案，患者随机分组后至少需住院治疗 2 周。主要终点为从基线到第 4 周时阳性和阴性综合征量表总分（PANSST）的组内变化。次要分析包括从基线开始在不同时间点的组内和组间变化。监测不良事件（AE）和实验室数据。

结果

共有 200 例患者被随机分组（AL，n=99；PP，n=101）；分别有 56.6%和 42.6%的患者完成了研究。对于 AL，基线时 PANSST 的平均基线值为 94.1；从第 4 周开始（-17.4；P<.001），评分显著降低，第 9 周（-19.8）和第 25 周（-23.3）也降低。对于 PP，从基线开始（94.6），第 4 周（-20.1；P<.001）时 PANSST 也显著改善，第 9 周（-22.5）和第 25 周（-21.7）也有所改善。AL 组在 25 周内最常见的 3 种 AE 为注射部位疼痛（17.2%）、体重增加（9.1%）和静坐不能（9.1%）。PP 组最常见的同样的 AE（注射部位疼痛[24.8%]、体重增加[16.8%]和静坐不能[10.9%]）。