Savitz Adam J, Xu Haiyan, Gopal Srihari, Nuamah Isaac, Ravenstijn Paulien, Hough David, Hargarter Ludger
Janssen Research & Development, LLC, Raritan, NJ, USA,
Janssen Research & Development, a Division of Janssen Pharmaceutica NV, Beerse, Belgium.
Neuropsychiatr Dis Treat. 2019 Feb 21;15:587-602. doi: 10.2147/NDT.S189668. eCollection 2019.
This randomized, double-blind (DB), non-inferiority phase 3 study was conducted to assess the efficacy and safety of paliperidone palmitate 3-month (PP3M) vs 1-month formulation (PP1M) in European and non-European patients with schizophrenia.
In this randomized, DB, parallel-group study, adult patients (18-70 years) with schizophrenia (per DSM-IV-TR) having Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120; previously stabilized on PP1M were enrolled. The study had 4 phases: screening (3 weeks), open-label (OL) stabilization (17 weeks), DB (48 weeks) and follow-up (4-12 weeks) phase. Patients were treated with fixed-dose PP3M (175-525 mg eq deltoid/gluteal) or PP1M (50-150 mg eq deltoid/gluteal) for 48 weeks in DB phase.
In total, 487 European (PP3M, n=242; PP1M, n=245) and 508 non-European patients (PP3M, n=241; PP1M, n=267) entered DB phase (modified intent-to-treat (mITT) [DB] analysis set). Among the 508 non-European patients in mITT set, 67.7% were from Asia (n=344) and 32.3% were from rest of world (ROW, n=164). During the DB phase, similar percentage of Europeans (PP3M: 7%; PP1M: 8%) and non-Europeans (PP3M: 9%; PP1M: 10%) experienced relapse (Kaplan-Meier estimate PP3M-PP1M [95% CI] of percentage of relapse-free patients at the end of DB phase [primary endpoint]: European: 1.0% [-4.3%; 6.2%]; non-European: 1.4% [-4.4%; 7.1%]; Asian: 1.6% [-5.7%; 9.0%]; and ROW: 1.4% [-7.0%, 9.8%], per-protocol analysis set). Incidence of treatment-emergent adverse events (TEAEs) was lower in Europeans (PP3M: 56%, PP1M: 59%) than non-Europeans (PP3M: 80%, PP1M: 73%). The most commonly reported TEAE was weight gain.
PP3M showed similar efficacy to PP1M in Europeans and non-Europeans, consistent with non-inferiority of PP3M to PP1M observed in overall population. Rates of AEs were higher in non-Europeans. However, weight gain was greater in non-Europeans, especially the Asian population.
本随机、双盲（DB）、非劣效性3期研究旨在评估棕榈酸帕利哌酮3个月剂型（PP3M）与1个月剂型（PP1M）在欧洲和非欧洲精神分裂症患者中的疗效和安全性。
在这项随机、双盲、平行组研究中，纳入了年龄在18至70岁之间、符合《精神疾病诊断与统计手册第四版，修订版》（DSM-IV-TR）标准、阳性与阴性症状量表（PANSS）总分在70至120之间、之前使用PP1M病情已稳定的精神分裂症成年患者。该研究有4个阶段：筛查（3周）、开放标签（OL）稳定期（17周）、双盲期（48周）和随访期（4至12周）。在双盲期，患者接受固定剂量的PP3M（175 - 525 mg等效剂量，三角肌/臀肌注射）或PP1M（50 - 150 mg等效剂量，三角肌/臀肌注射）治疗48周。
共有487名欧洲患者（PP3M组，n = 242；PP1M组，n = 245）和508名非欧洲患者（PP3M组，n = 241；PP1M组，n = 267）进入双盲期（改良意向性治疗（mITT）[双盲]分析集）。在mITT集中的508名非欧洲患者中，67.7%来自亚洲（n = 344），32.3%来自世界其他地区（ROW，n = 164）。在双盲期，欧洲患者（PP3M组：7%；PP1M组：8%）和非欧洲患者（PP3M组：9%；PP1M组：10%）经历复发的比例相似（双盲期末无复发患者百分比的Kaplan-Meier估计PP3M - PP1M[95%置信区间] [主要终点]：欧洲：1.0% [-4.3%；6.2%]；非欧洲：1.4% [-4.4%；7.1%]；亚洲：1.6% [-5.7%；9.0%]；ROW：1.4% [-7.0%，9.8%]，符合方案分析集）。欧洲患者（PP3M组：56%，PP1M组：59%）治疗中出现的不良事件（TEAE）发生率低于非欧洲患者（PP3M组：80%，PP1M组：73%）。最常报告的TEAE是体重增加。
PP3M在欧洲人和非欧洲人中显示出与PP1M相似的疗效，这与在总体人群中观察到的PP3M不劣于PP1M一致。非欧洲人的不良事件发生率较高。然而，非欧洲人，尤其是亚洲人群体重增加更明显。
