University of Kansas Medical Center, Kansas City, KS, USA.
University of South Florida, Tampa, FL, USA.
Parkinsonism Relat Disord. 2014 Feb;20(2):142-8. doi: 10.1016/j.parkreldis.2013.08.017. Epub 2013 Sep 5.
IPX066 is an extended release carbidopa/levodopa formulation designed to rapidly attain and maintain therapeutic plasma concentrations for a prolonged duration, allowing dosing intervals of approximately 6 h. The objective was to assess the efficacy, safety, and impact on quality of life of IPX066 in the treatment of levodopa-naive Parkinson's disease (PD) patients.
This was a randomized, double-blind, placebo-controlled, 30-week study of 381 levodopa-naïve patients assigned to placebo or IPX066 containing 145, 245 or 390 mg of levodopa administered three times daily (TID). The primary efficacy measure was change from Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (Part II) + motor scores (Part III), at 30 weeks. Secondary outcome measures included UPDRS total and subscores, patient and clinician global impressions (PGI-I, CGI-I), and the Parkinson's Disease Questionnaire (PDQ-39).
All IPX066 dosages were superior to placebo throughout the study and at 30 weeks (P < 0.0001). The mean improvement in UPDRS Parts II + III at 30 weeks compared to baseline was 11.7, 12.9, and 14.9 points for the three dosages and 0.6 points for placebo (P < 0.0001, all dosages). PDQ-39 total scores improved with IPX066 (P ≤ 0.034, all dosages). The most commonly reported adverse events with IPX066 included nausea, dizziness, and headache. No unexpected drug-related serious adverse events were reported.
IPX066 provided significant clinical benefits at the three dosages tested compared to placebo and was well tolerated in levodopa-naive PD patients. Of the dosages tested, IPX066 145 mg TID appeared to provide the best overall balance between efficacy and safety.
IPX066 是一种延长释放的卡比多巴/左旋多巴制剂,旨在快速达到并维持治疗性血浆浓度,延长时间,使给药间隔约为 6 小时。目的是评估 IPX066 在治疗左旋多巴初治帕金森病(PD)患者中的疗效、安全性和对生活质量的影响。
这是一项为期 30 周的随机、双盲、安慰剂对照研究,共纳入 381 名左旋多巴初治患者,随机分为安慰剂组或 IPX066 组,其中 IPX066 组含有 145、245 或 390 mg 的左旋多巴,每日 3 次(TID)给药。主要疗效指标为 30 周时与基线相比,统一帕金森病评定量表(UPDRS)日常生活活动(第 II 部分)+运动评分(第 III 部分)的变化。次要结局指标包括 UPDRS 总分和各分量表、患者和医生整体印象(PGI-I、CGI-I)以及帕金森病问卷(PDQ-39)。
在整个研究过程中和 30 周时,所有 IPX066 剂量均优于安慰剂(P<0.0001)。与基线相比,30 周时 UPDRS 第 II 部分+III 部分的平均改善为 11.7、12.9 和 14.9 分,三个剂量组和安慰剂组分别为 0.6 分(P<0.0001,所有剂量组)。PDQ-39 总分随 IPX066 改善(P≤0.034,所有剂量组)。与 IPX066 相关的最常见不良事件包括恶心、头晕和头痛。未报告与药物相关的严重不良事件。
与安慰剂相比,在测试的三种剂量下,IPX066 均提供了显著的临床获益,且在左旋多巴初治 PD 患者中具有良好的耐受性。在测试的剂量中,IPX066 145 mg TID 似乎在疗效和安全性之间提供了最佳的整体平衡。