Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, New Jersey, USA.
Schizophr Res. 2010 Feb;116(2-3):107-17. doi: 10.1016/j.schres.2009.10.026. Epub 2009 Dec 2.
We assessed efficacy and tolerability of the injectable atypical antipsychotic paliperidone palmitate in delaying time-to-relapse in adults with schizophrenia.
Eligible patients (Positive and Negative Syndrome Scale [PANSS] total score < 120) were transitioned from previous antipsychotics to paliperidone palmitate during a 9-week, open-label phase. Patients received the first 2 intramuscular injections of paliperidone palmitate (50mg eq) one-week apart, then subsequent injections (25, 50, or 100mg eq, flexibly-dosed), once-monthly. Stable patients (PANSS total score < or = 75) continued into the 24-week maintenance phase. At maintenance phase endpoint, stabilized patients were randomized (1:1 ratio) to either continue paliperidone palmitate (at stabilized dose) or begin placebo in the variable-duration, double-blind phase.
The preplanned interim analysis (conducted after 68 relapse events) included 312 patients: mean age = 40 years, 55% men, 66% white, and mean transition baseline PANSS total score (SD): placebo, 69.5 (16.89); paliperidone palmitate, 69.3 (17.39). Time-to-relapse (primary endpoint) favored paliperidone palmitate (p<0.0001, log-rank test) at interim and final analysis (n=408). The hazard ratio (placebo/paliperidone palmitate) at the final analysis was 3.60 (95% CI: 2.45, 5.28). Treatment-emergent adverse event rates (final analysis set) were: 67% for transition and maintenance phases, and 45% (placebo) and 44% (paliperidone palmitate) for the double-blind phase. Across phases, the incidence of glucose-related adverse events was low (< or = 4%), while mean weight increased by 1.9 kg for paliperidone palmitate and remained unchanged for placebo patients. Injection site tolerability was comparable between groups.
Paliperidone palmitate significantly delayed time-to-relapse compared with placebo and presented no new safety signals.
我们评估了可注射性非典型抗精神病药棕榈酸帕利哌酮在延迟精神分裂症成人复发时间方面的疗效和耐受性。
符合条件的患者（阳性和阴性症状量表[PANSS]总分<120）在 9 周的开放标签期内从之前的抗精神病药物转换为棕榈酸帕利哌酮。患者接受第 1 次和第 2 次间隔一周的 2 次肌肉注射棕榈酸帕利哌酮（50mg 等效），然后进行后续注射（25、50 或 100mg 等效，灵活剂量），每月 1 次。稳定的患者（PANSS 总分<或=75）继续进入 24 周的维持期。在维持期终点，稳定的患者以 1:1 的比例随机（随机分配）继续接受棕榈酸帕利哌酮（稳定剂量）或在可变持续时间的双盲期开始安慰剂。
该预先计划的中期分析（在 68 例复发事件后进行）纳入了 312 名患者：平均年龄为 40 岁，55%为男性，66%为白人，平均过渡基线 PANSS 总分（SD）：安慰剂，69.5（16.89）；棕榈酸帕利哌酮，69.3（17.39）。在中期和最终分析（n=408）中，复发时间（主要终点）有利于棕榈酸帕利哌酮（p<0.0001，对数秩检验）。最终分析时的风险比（安慰剂/棕榈酸帕利哌酮）为 3.60（95%CI：2.45，5.28）。治疗期不良事件发生率（最终分析集）为：转换和维持期为 67%，双盲期为 45%（安慰剂）和 44%（棕榈酸帕利哌酮）。各阶段葡萄糖相关不良事件的发生率均较低（<或=4%），而棕榈酸帕利哌酮组的平均体重增加 1.9 公斤，安慰剂组无变化。注射部位耐受性在两组间相当。
与安慰剂相比，棕榈酸帕利哌酮显著延迟了复发时间，且未出现新的安全性信号。
