Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USA.
ACADIA Pharmaceuticals Inc., San Diego, CA, USA.
J Parkinsons Dis. 2020;10(4):1389-1396. doi: 10.3233/JPD-202047.
Parkinson's disease psychosis (PDP) is a common nonmotor symptom that affects up to 60% of patients. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, is approved for treating hallucinations and delusions associated with PDP.
Evaluate the efficacy and tolerability of pimavanserin in an open-label extension (OLE) study.
Patients completing a pivotal 6-week placebo-controlled trial (Core Study) could enroll in the OLE. All patients pimavanserin 34 mg once daily, blinded to previous treatment allocation. Prespecified blinded assessments at Week 4 were the Scale for the Assessment of Positive Symptoms (SAPS) PD version and SAPS H + D scales, Caregiver Burden Scale (CBS), and Clinical Global Impression (CGI) Improvement and Severity scales.
Of 171 who entered the OLE, 148 (87%) completed Week 4. Among patients who received placebo in the Core Study, mean (SD) change from OLE baseline to OLE Week 4 for the SAPS-PD was - 3.4 (6.3); p < 0.0001. Mean change from Core Study baseline to OLE Week 4 for SAPS-PD was similar among prior pimavanserin- and placebo-treated patients (-6.9 vs. -6.3). Improvement was similar with CGI-I, CGI-S, CBS, and SAPS-H + D in patients previously treated with placebo. Adverse events occurred in 92 (53.8%) patients during the 4-week OLE.
Improvements at OLE Week 4 from pretreatment baseline were similar with placebo and pimavanserin in the Core Study. The beneficial effects observed with pimavanserin in the 6-week Core Study were maintained for 4 weeks in the blinded OLE, supporting the durability of response with pimavanserin 34 mg for PDP over 10 weeks.
帕金森病精神病（PDP）是一种常见的非运动症状，影响多达 60%的患者。Pimavanserin 是一种选择性 5-HT2A 反向激动剂/拮抗剂，已被批准用于治疗与 PDP 相关的幻觉和妄想。
评估 pimavanserin 在开放标签扩展（OLE）研究中的疗效和耐受性。
完成关键 6 周安慰剂对照试验（核心研究）的患者可以入组 OLE。所有患者均接受 pimavanserin 34mg 每日一次，对先前的治疗分配保持盲法。第 4 周进行了预设的盲法评估，包括阳性症状评定量表（SAPS）PD 版本和 SAPS H+D 量表、照顾者负担量表（CBS）和临床总体印象（CGI）改善和严重程度量表。
171 名进入 OLE 的患者中，有 148 名（87%）完成了第 4 周。在核心研究中接受安慰剂的患者中，从 OLE 基线到 OLE 第 4 周，SAPS-PD 的平均（SD）变化为-3.4（6.3）；p<0.0001。从核心研究基线到 OLE 第 4 周，SAPS-PD 的变化在先前接受 pimavanserin 和安慰剂治疗的患者中相似（-6.9 与-6.3）。CGI-I、CGI-S、CBS 和 SAPS-H+D 的改善在先前接受安慰剂治疗的患者中相似。在 4 周的 OLE 期间，92 名（53.8%）患者发生了不良反应。
从治疗前基线到 OLE 第 4 周的改善，安慰剂和核心研究中的 pimavanserin 相似。在核心研究中，pimavanserin 在 6 周内观察到的有益效果在盲法 OLE 中持续了 4 周，支持了 pimavanserin 34mg 治疗 PDP 超过 10 周的反应持久性。
