Precise Research Centers, Flowood, MS 39232, USA.
Bipolar Disord. 2012 Feb;14(1):31-40. doi: 10.1111/j.1399-5618.2011.00975.x.
The present study evaluated inhaled loxapine for the acute treatment of agitation in patients with bipolar I disorder.
A Phase 3, randomized, double blind, placebo-controlled, parallel group inpatient study was performed at 17 psychiatric research facilities. Agitated patients (N=314) with bipolar I disorder (manic or mixed episodes) were randomized (1:1:1) to inhaled loxapine 5 mg or 10 mg, or inhaled placebo using the Staccato® system. Following baseline assessments, patients received Dose 1 and were evaluated for 24 hours. If required, up to two additional doses of study drug and/or lorazepam rescue medication were given. The primary efficacy endpoint was change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) score two hours after Dose 1. The key secondary endpoint was the Clinical Global Impression-Improvement score at two hours after Dose 1. Additional endpoints included the changes from baseline in the PANSS-EC from 10 min through 24 hours after Dose 1. Safety was assessed by adverse events, vital signs, physical examinations, and laboratory tests.
For the primary and key secondary endpoints, both doses of inhaled loxapine significantly reduced agitation compared with placebo. Reduced agitation, as reflected in PANSS-EC score, was evident 10 min after Dose 1 with both doses. Inhaled loxapine was well tolerated, and the most common adverse events were known effects of loxapine or minor oral effects common with inhaled medications (dysgeusia was reported in 17% of patients receiving active drug versus 6% receiving placebo).
Inhaled loxapine provided a rapid, non-injection, well-tolerated acute treatment for agitation in patients with bipolar I disorder.
本研究评估了洛沙平吸入剂治疗双相 I 型障碍患者激越的急性疗效。
在 17 家精神病学研究机构进行了一项 3 期、随机、双盲、安慰剂对照、平行分组的住院研究。将 314 例患有双相 I 型障碍（躁狂或混合发作）的激越患者（1:1:1）随机分为洛沙平吸入 5mg 或 10mg 组或吸入安慰剂组，采用 Staccato®系统给药。在基线评估后，患者接受第 1 剂，并在 24 小时内进行评估。如果需要，给予最多两剂研究药物和/或劳拉西泮解救药物。主要疗效终点是第 1 剂后 2 小时从基线变化的阳性和阴性综合征量表-兴奋成分（PANSS-EC）评分。关键次要终点是第 1 剂后 2 小时的临床总体印象-改善评分。其他终点包括第 1 剂后 10 分钟至 24 小时从基线变化的 PANSS-EC。安全性通过不良事件、生命体征、体格检查和实验室检查进行评估。
对于主要和关键次要终点，两种剂量的洛沙平吸入剂与安慰剂相比均显著减轻激越。两种剂量均在第 1 剂后 10 分钟即可观察到 PANSS-EC 评分的激越减轻。洛沙平吸入剂耐受性良好，最常见的不良事件是洛沙平的已知作用或吸入药物常见的轻微口腔作用（味觉障碍在接受活性药物的患者中发生率为 17%，而接受安慰剂的患者中为 6%）。
洛沙平吸入剂为双相 I 型障碍患者的激越提供了一种快速、非注射、耐受性良好的急性治疗方法。
