Durgam Suresh, Landbloom Ronald P, Mackle Mary, Wu Xiao, Mathews Maju, Nasrallah Henry A
Allergan Inc, Jersey City.
Merck, Whitehouse Station.
Neuropsychiatr Dis Treat. 2017 Jul 31;13:2021-2035. doi: 10.2147/NDT.S130211. eCollection 2017.
The primary objective of this study was to assess long-term safety with sublingual asenapine 2.5 or 5 mg twice daily (BID) in patients with schizophrenia.
Actively treated patients on asenapine 2.5 mg BID, asenapine 5 mg BID, or olanzapine 15 mg once daily (QD) who completed a 6-week randomized, double-blind, placebo- and olanzapine-controlled study continued lead-in treatment in this 26-week, multicenter, double-blind, double-dummy, olanzapine-controlled Phase IIIB extension study; placebo patients were assigned to asenapine 2.5 mg BID treatment. Safety analyses were based on the all treated set (patients who received one or more doses of extension trial medication); change from baseline analyses used the acute study baseline. Treatment-emergent adverse events (TEAEs) and changes in laboratory parameters were monitored; weight change for asenapine versus olanzapine was the key secondary objective. Descriptive statistics were used; weight change was analyzed using a mixed-model repeated-measure approach.
Of the 120 patients in the all-treated set, 60% completed treatment (asenapine 2.5 mg BID 66.1% overall, asenapine 5 mg BID 52.4%, olanzapine 15 mg QD 56.3%). The incidence of TEAEs was higher for placebo patients from the lead-in study who switched to asenapine 2.5 mg BID for extension treatment (71.0%) versus patients continuing asenapine 2.5 mg BID (38.7%), asenapine 5 mg BID (38.1%), or olanzapine 15 mg QD (25.0%). The most common TEAE (≥5% in every group) was worsening of schizophrenia. Least squares mean change in body weight from the acute study baseline to week 26 was +0.6 kg for overall asenapine 2.5 mg BID, +0.8 kg for asenapine 5 mg BID, and +1.2 kg for olanzapine 15 mg QD. There were no clinically relevant changes in metabolic parameters; values were generally similar across treatment groups.
Asenapine 2.5 mg BID and 5 mg BID were generally well tolerated in long-term treatment. Weight gain was less for overall asenapine 2.5 mg BID and 5 mg BID than for olanzapine 15 mg QD.
本研究的主要目的是评估每日两次（BID）舌下含服阿立哌唑2.5毫克或5毫克对精神分裂症患者的长期安全性。
在一项为期6周的随机、双盲、安慰剂和奥氮平对照研究中，接受阿立哌唑2.5毫克BID、阿立哌唑5毫克BID或奥氮平15毫克每日一次（QD）积极治疗并完成研究的患者，继续参与这项为期26周、多中心、双盲、双模拟、奥氮平对照的IIIB期扩展研究；安慰剂组患者被分配接受阿立哌唑2.5毫克BID治疗。安全性分析基于所有接受治疗的患者（接受过一剂或多剂扩展试验药物的患者）；从基线变化分析使用急性研究的基线数据。监测治疗中出现的不良事件（TEAE）和实验室参数变化；阿立哌唑与奥氮平的体重变化是关键次要目标。采用描述性统计；体重变化采用混合模型重复测量方法进行分析。
在所有接受治疗的120例患者中，60%完成了治疗（阿立哌唑2.5毫克BID总体完成率为66.1%，阿立哌唑5毫克BID为52.4%，奥氮平15毫克QD为56.3%）。导入期研究中改用阿立哌唑2.5毫克BID进行扩展治疗的安慰剂组患者的TEAE发生率（71.0%）高于继续接受阿立哌唑2.5毫克BID（38.7%）、阿立哌唑5毫克BID（38.1%）或奥氮平15毫克QD（25.0%）治疗的患者。最常见的TEAE（每组≥5%）是精神分裂症病情恶化。从急性研究基线到第26周，阿立哌唑2.5毫克BID总体体重的最小二乘均值变化为+0.6千克，阿立哌唑5毫克BID为+0.8千克，奥氮平15毫克QD为+1.2千克。代谢参数无临床相关变化；各治疗组数值总体相似。
阿立哌唑2.5毫克BID和5毫克BID在长期治疗中总体耐受性良好。阿立哌唑2.5毫克BID和5毫克BID总体的体重增加少于奥氮平15毫克QD。
