Rocha José-Francisco, Ebersbach Georg, Lees Andrew, Tolosa Eduardo, Ferreira Joaquim J, Poewe Werner, Rascol Olivier, Stocchi Fabrizio, Antonini Angelo, Magalhães Diogo, Gama Helena, Soares-da-Silva Patrício
BIAL-Portela & Ca S.A., Coronado, Portugal.
Movement Disorders Clinic, Beelitz-Heilstätten, Germany.
Front Neurol. 2022 Aug 23;13:994114. doi: 10.3389/fneur.2022.994114. eCollection 2022.
analyses of the BIPARK-I and II trials previously demonstrated that opicapone (OPC) 50 mg was efficacious over the whole trajectory of motor fluctuation evolution in patients with Parkinson's disease (PD) and end-of-dose motor fluctuations, with enhanced efficacy in patients who were earlier vs. later in their disease course and levodopa treatment pathway. Complementary analyses were performed to evaluate the safety/tolerability of OPC following the same pre-defined segmentation of the wide spectrum of duration of both PD and levodopa therapy, as well as of motor fluctuation history, in this patient population.
Data from matching treatment arms in BIPARK-I and II were combined for the placebo (PLC) and OPC 50 mg groups and exploratory analyses were performed to investigate the safety/tolerability of OPC 50 mg and PLC in 22 subgroups of patients who were in "earlier" vs. "later" stages of both their disease course (e.g., duration of PD <6 years vs. ≥6 years) and levodopa treatment pathway (e.g., levodopa treatment duration <4 vs. ≥4 years). Safety/tolerability assessments included evaluation of treatment-emergent adverse events (TEAEs).
The Safety Set included 522 patients (PLC, = 257; OPC 50 mg, = 265). For OPC 50 mg, incidences of TEAEs, related TEAEs, related serious TEAEs, and related TEAEs leading to discontinuation were lower for patients in earlier vs. later stages of their disease course and levodopa treatment pathway in 86.4, 86.4, 63.6, and 68.2% of the 22 pairwise comparisons conducted, respectively (compared with 63.6, 77.3, 18.2, and 45.5%, respectively, in the 22 corresponding PLC comparisons).
OPC 50 mg was generally well-tolerated when used to treat patients with PD with end-of-dose fluctuations, with an even more favorable tolerability profile in patients who were earlier, as opposed to later, in their disease course and levodopa treatment pathway, further supporting its use as an early adjunct to levodopa in PD.
对BIPARK-I和II试验的分析先前已表明，50毫克奥匹卡朋（OPC）在帕金森病（PD）患者和剂末运动波动的整个运动波动演变过程中均有效，且在疾病进程和左旋多巴治疗路径中处于早期而非晚期的患者中疗效增强。在该患者群体中，进行了补充分析，以按照PD和左旋多巴治疗持续时间的广泛范围以及运动波动病史的相同预定义分段来评估OPC的安全性/耐受性。
将BIPARK-I和II中匹配治疗组的数据合并到安慰剂（PLC）组和50毫克OPC组，并进行探索性分析，以研究50毫克OPC和PLC在疾病进程（例如，PD病程<6年与≥6年）和左旋多巴治疗路径（例如，左旋多巴治疗持续时间<4年与≥4年）处于“早期”与“晚期”的22个患者亚组中的安全性/耐受性。安全性/耐受性评估包括对治疗中出现的不良事件（TEAE）的评估。
安全集包括522名患者（PLC组 = 257名；50毫克OPC组 = 265名）。对于50毫克OPC，在进行的22对比较中，疾病进程和左旋多巴治疗路径处于早期的患者中，TEAE、相关TEAE、相关严重TEAE以及导致停药的相关TEAE的发生率分别在86.4%、86.4%、63.6%和68.2%的比较中低于晚期患者（相比之下，在22次相应的PLC比较中分别为63.6%、77.3%、18.2%和45.5%）。
50毫克OPC用于治疗有剂末波动的PD患者时总体耐受性良好，在疾病进程和左旋多巴治疗路径中处于早期而非晚期的患者中耐受性更优，进一步支持其作为PD中左旋多巴的早期辅助药物使用。
