Garcia-Borreguero Diego, Allen Richard, Hudson John, Dohin Elisabeth, Grieger Frank, Moran Kimberly, Schollmayer Erwin, Smit René, Winkelman John
a a Sleep Research Institute , Madrid , Spain.
b b Department of Neurology , Johns Hopkins Bayview Medical Center , Baltimore , MD , USA.
Curr Med Res Opin. 2016;32(1):77-85. doi: 10.1185/03007995.2015.1103216. Epub 2015 Nov 16.
This 12 week double-blind, placebo-controlled study (ClinicalTrials.gov: NCT01569464) was conducted to evaluate the effects of rotigotine transdermal patch on daytime symptoms in patients with idiopathic restless legs syndrome (RLS).
Adult patients with moderate-to-severe RLS were randomized to rotigotine (optimal dose: 1-3 mg/24 h) or placebo. A modified four-assessment version (4:00 pm, 6:00 pm, 8:00 pm, and 10:00 pm) of the Multiple Suggested Immobilization Test (m-SIT) was performed at baseline and end of 4 week maintenance (EoM). Primary study outcomes were change from baseline to EoM in International Restless Legs Syndrome Rating Scale (IRLS) and in average of means for the m-SIT Discomfort Scale (m-SIT-DS) (combined average of mean values from each of the individual assessments). Secondary outcomes included average of means of Periodic Limb Movement during Wakefulness Index (PLMWI; PLM/hour) for the combination of m-SIT.
A total of 150 patients were randomized and 137 (rotigotine: 92/101 [91.1%]; placebo: 45/49 [91.8%]) completed maintenance. All 150 randomized patients were assessed for efficacy. At EoM, mean change in IRLS was -14.9 ± 9.3 with rotigotine vs. -12.7 ± 7.6 with placebo (ANCOVA, LS mean treatment difference [95% CI]: -0.27 [-2.96, 2.42]; p = 0.8451). Changes in average of means of m-SIT-DS values of each individual SIT were comparable with rotigotine (-2.68 ± 2.31) vs. placebo (-2.62 ± 2.61) (ANCOVA, LS mean treatment difference [95% CI]: 0.07 [-0.61, 0.75]; p = 0.8336) and comparable reductions in PLMWI were observed in both treatment groups (8.34 [-8.50, 25.17]; p = 0.3290). Rotigotine was generally well tolerated. Application site reactions (rotigotine: 20 patients [19.8%]; placebo: 4 [8.2%]) and nausea (16 [15.8%]; 3 [6.1%]) were the most common AEs.
Rotigotine was beneficial in improving overall RLS symptom severity (assessed by IRLS) and RLS symptom severity at various times of the day (m-SIT-DS); however, superiority to placebo was not established.
本为期12周的双盲、安慰剂对照研究（ClinicalTrials.gov：NCT01569464）旨在评估罗替戈罗替戈汀透皮贴剂对特发性不宁腿综合征（RLS）患者日间症状的影响。
中度至重度RLS成年患者被随机分为罗替戈汀组（最佳剂量：1 - 3mg/24小时）或安慰剂组。在基线和4周维持期末（EoM）进行改良的四重评估版（下午4:00、6:00、8:00和10:00）多次建议固定试验（m - SIT）。主要研究结局为从基线到EoM时国际不宁腿综合征评定量表（IRLS）以及m - SIT不适量表（m - SIT - DS）平均值的变化（各单次评估平均值的综合平均值）。次要结局包括m - SIT组合的清醒期周期性肢体运动指数（PLMWI；每小时PLM次数）的平均值。
共150例患者被随机分组，137例（罗替戈汀组：92/101 [91.1%]；安慰剂组：45/49 [91.8%]）完成维持期治疗。对所有150例随机分组患者进行了疗效评估。在EoM时，罗替戈汀组IRLS的平均变化为 - 14.9 ± 9.3，安慰剂组为 - 12.7 ± 7.6（协方差分析，最小二乘均数治疗差异[95%置信区间]： - 0.27 [- 2.96, 2.42]；p = 0.8451）。各单次SIT的m - SIT - DS值平均值变化在罗替戈汀组（ - 2.68 ± 2.31）与安慰剂组（ - 2.62 ± 2.61）之间具有可比性（协方差分析，最小二乘均数治疗差异[95%置信区间]：0.07 [- 0.61, 0.75]；p = 0.8336），且两个治疗组在PLMWI方面均观察到类似程度的降低（8.34 [- 8.50, 25.17]；p = 0.3290）。罗替戈汀总体耐受性良好。应用部位反应（罗替戈汀组：20例患者[19.8%]；安慰剂组：4例[8.2%]）和恶心（16例[15.8%]；3例[6.1%]）是最常见的不良事件。
罗替戈汀有助于改善整体RLS症状严重程度（通过IRLS评估）以及一天中不同时间的RLS症状严重程度（m - SIT - DS）；然而，未证实其优于安慰剂。
