LeWitt Peter A, Verhagen Metman Leo, Rubens Robert, Khanna Sarita, Kell Sherron, Gupta Suneel
Clin Neuropharmacol. 2018 Mar/Apr;41(2):47-55. doi: 10.1097/WNF.0000000000000269.
Extended-release (ER) carbidopa-levodopa (CD-LD) (IPX066/RYTARY/NUMIENT) produces improvements in "off" time, "on" time without troublesome dyskinesia, and Unified Parkinson Disease Rating Scale scores compared with immediate-release (IR) CD-LD or IR CD-LD plus entacapone (CLE). Post hoc analyses of 2 ER CD-LD phase 3 trials evaluated whether the efficacy and safety of ER CD-LD relative to the respective active comparators were altered by concomitant medications (dopaminergic agonists, monoamine oxidase B [MAO-B] inhibitors, or amantadine).
ADVANCE-PD (n = 393) assessed safety and efficacy of ER CD-LD versus IR CD-LD. ASCEND-PD (n = 91) evaluated ER CD-LD versus CLE. In both studies, IR- and CLE-experienced patients underwent a 6-week, open-label dose-conversion period to ER CD-LD prior to randomization. For analysis, the randomized population was divided into 3 subgroups: dopaminergic agonists, rasagiline or selegiline, and amantadine. For each subgroup, changes from baseline in PD diary measures ("off" time and "on" time with and without troublesome dyskinesia), Unified Parkinson Disease Rating Scale Parts II + III scores, and adverse events were analyzed, comparing ER CD-LD with the active comparator.
Concomitant dopaminergic agonist or MAO-B inhibitor use did not diminish the efficacy (improvement in "off" time and "on" time without troublesome dyskinesia) of ER CD-LD compared with IR CD-LD or CLE, whereas the improvement with concomitant amantadine failed to reach significance. Safety and tolerability were similar among the subgroups, and ER CD-LD did not increase troublesome dyskinesia. For patients on oral LD regimens and taking a dopaminergic agonist, and/or a MAO-B inhibitor, changing from an IR to an ER CD-LD formulation provides approximately an additional hour of "good" on time.
与速释型卡比多巴-左旋多巴（CD-LD）或速释型CD-LD加恩他卡朋（CLE）相比，缓释型（ER）卡比多巴-左旋多巴（IPX066/RYTARY/NUMIENT）可改善“关”期时间、无麻烦异动症的“开”期时间以及统一帕金森病评定量表评分。两项ER CD-LD 3期试验的事后分析评估了与各自活性对照药相比，ER CD-LD的疗效和安全性是否会因合并用药（多巴胺能激动剂、单胺氧化酶B[MAO-B]抑制剂或金刚烷胺）而改变。
ADVANCE-PD研究（n = 393）评估了ER CD-LD与速释型CD-LD的安全性和疗效。ASCEND-PD研究（n = 91）评估了ER CD-LD与CLE的疗效。在两项研究中，有速释型和CLE用药经验的患者在随机分组前接受了为期6周的开放标签剂量转换期，转换为ER CD-LD。为进行分析，将随机分组的人群分为3个亚组：多巴胺能激动剂组、雷沙吉兰或司来吉兰组以及金刚烷胺组。对每个亚组，分析帕金森病日记测量指标（有或无麻烦异动症的“关”期时间和“开”期时间）、统一帕金森病评定量表第二部分+第三部分评分以及不良事件相对于基线的变化，比较ER CD-LD与活性对照药。
与速释型CD-LD或CLE相比，合并使用多巴胺能激动剂或MAO-B抑制剂并未降低ER CD-LD的疗效（改善“关”期时间和无麻烦异动症的“开”期时间），而合并使用金刚烷胺时的改善未达到显著水平。各亚组之间的安全性和耐受性相似，且ER CD-LD未增加麻烦的异动症。对于接受口服左旋多巴治疗方案并服用多巴胺能激动剂和/或MAO-B抑制剂的患者，从速释型转换为ER CD-LD制剂可使“良好”的开期时间大约增加1小时。
