长效帕利哌酮 6 个月制剂的长期疗效和安全性：一项为期 1 年的成人精神分裂症双盲研究的 2 年开放性扩展研究。
Long-Term Efficacy and Safety of Paliperidone 6-Month Formulation: An Open-Label 2-Year Extension of a 1-Year Double-Blind Study in Adult Participants With Schizophrenia.
机构信息
Janssen Scientific Affairs, LLC, Titusville, New Jersey, USA.
Janssen Research & Development, LLC, Titusville, New Jersey, USA.
出版信息
Int J Neuropsychopharmacol. 2023 Aug 29;26(8):537-544. doi: 10.1093/ijnp/pyad028.
BACKGROUND
Paliperidone palmitate 6-month (PP6M) demonstrated noninferiority to paliperidone palmitate 3-month in preventing relapse in patients with schizophrenia in a phase 3 double-blind (DB) study (NCT03345342). Here, we report long-term efficacy and safety results from a 2-year single-arm, open-label extension (OLE; NCT04072575) of this DB study.
METHODS
Participants who completed the DB study without relapse were enrolled and followed-up every 3 months up to 2 years. Participants received 4 PP6M gluteal injections (700/1000 mg eq.) at baseline, 6-month, 12-month, and 18-month visits. Efficacy endpoints included assessment of relapse, Positive and Negative Syndrome Scale total score, Personal and Social Performance score, and Clinical Global Impression-Severity scale change from baseline. Safety was assessed by treatment-emergent adverse events (TEAEs), physical examinations, and laboratory tests.
RESULTS
Of 178 participants enrolled, 154 (86.5%) completed the OLE (mean age: 40.4 years, men: 70.8%; mean duration of PP6M exposure during OLE: 682.1 days). Overall, 7/178 (3.9%) participants relapsed between 20 and 703 days after enrolment. Mean (SD) changes from baseline to endpoint were as follows: Positive and Negative Syndrome Scale total score, 0.7 (8.22); Clinical Global Impression-Severity, 0.0 (0.51); and Personal and Social Performance Scale, 0.5 (7.47). Overall, 111/178 participants (62.4%) reported ≥1 TEAE; most common (>5%) TEAEs were headache (13.5%) and increased blood prolactin/hyperprolactinemia (18.0%); 8/178 (4.5%) participants experienced serious TEAEs, and 6/178 (3.4%) participants withdrew due to TEAEs. No deaths were reported.
CONCLUSIONS
The relapse rate observed with PP6M during the 2-year OLE was low (3.9%). Clinical and functional improvements demonstrated in the DB study were maintained during OLE, and no new safety concerns were identified.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04072575; EudraCT number: 2018-004532-30.
背景
在一项 3 期双盲（DB）研究（NCT03345342）中，棕榈酸帕利哌酮 6 个月（PP6M）在预防精神分裂症患者复发方面显示出非劣效性，优于棕榈酸帕利哌酮 3 个月。在这里，我们报告了这项 DB 研究的为期 2 年的单臂、开放标签扩展（OLE；NCT04072575）的长期疗效和安全性结果。
方法
在没有复发的情况下完成 DB 研究的参与者被招募并随访，直至 2 年。参与者在基线、6 个月、12 个月和 18 个月时接受 4 次臀部注射 PP6M（700/1000 mg eq.）。疗效终点包括评估复发、阳性和阴性综合征量表总分、个人和社会表现评分以及从基线开始的临床总体印象-严重程度量表变化。安全性通过治疗后出现的不良事件（TEAE）、体格检查和实验室检查来评估。
结果
在 178 名入组的参与者中，有 154 名（86.5%）完成了 OLE（平均年龄：40.4 岁，男性：70.8%；在 OLE 期间接受 PP6M 暴露的平均持续时间：682.1 天）。总体而言，7/178（3.9%）名参与者在入组后 20 至 703 天之间复发。从基线到终点的平均（SD）变化如下：阳性和阴性综合征量表总分，0.7（8.22）；临床总体印象-严重程度，0.0（0.51）；个人和社会表现量表，0.5（7.47）。总体而言，111/178 名参与者（62.4%）报告了≥1 次治疗后出现的不良事件；最常见（>5%）的不良事件为头痛（13.5%）和血催乳素升高/高催乳素血症（18.0%）；8/178 名（4.5%）参与者发生严重不良事件，6/178 名（3.4%）参与者因不良事件退出。没有死亡报告。
结论
在为期 2 年的 OLE 期间，PP6M 观察到的复发率较低（3.9%）。在 OLE 期间，DB 研究中观察到的临床和功能改善得到维持，未发现新的安全性问题。
试验注册
ClinicalTrials.gov 标识符：NCT04072575；EudraCT 编号：2018-004532-30。
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