一项评估加巴喷丁恩卡尼在不宁腿综合征患者中的疗效和耐受性的随机、双盲、安慰剂对照研究。
A randomized, double-blind, placebo-controlled study to assess the efficacy and tolerability of gabapentin enacarbil in subjects with restless legs syndrome.
机构信息
Sleep Disorders Center, East Carolina Neurology, Inc., Greenville, NC 27834, USA.
出版信息
J Clin Sleep Med. 2011 Jun 15;7(3):282-92. doi: 10.5664/JCSM.1074.
STUDY OBJECTIVE
To evaluate the efficacy and tolerability of gabapentin enacarbil (GEn) 1200 mg or 600 mg compared with placebo in subjects with moderate-to-severe primary restless legs syndrome (RLS).
METHODS
This 12-week, multicenter, double-blind, placebo-controlled study randomized subjects (1:1:1) to GEn 1200 mg, 600 mg, or placebo. Co-primary endpoints: mean change from baseline in International Restless Legs Scale (IRLS) total score and proportion of responders (rated as "very much" or "much" improved) on the investigator-rated Clinical Global Impression-Improvement scale (CGI-I) at Week 12 LOCF for GEn 1200 mg compared with placebo. Secondary endpoints included GEn 600 mg compared with placebo on the IRLS and CGI-I at Week 12 LOCF and subjective measures for sleep. Safety and tolerability assessments included adverse events.
RESULTS
325 subjects were randomized (GEn 1200 mg = 113; 600 mg = 115; placebo = 97). GEn 1200 mg significantly improved mean [SD] IRLS total score at Week 12 LOCF (baseline: 23.2 [5.32]; Week 12: 10.2 [8.03]) compared with placebo (baseline: 23.8 [4.58]; Week 12: 14.0 [7.87]; adjusted mean treatment difference [AMTD]: -3.5; p = 0.0015), and significantly more GEn 1200 mg-treated (77.5%) than placebo-treated (44.8%) subjects were CGI-I responders (p < 0.0001). Similar significant results were observed with GEn 600 mg for IRLS (AMTD: -4.3; p < 0.0001) and CGI-I (72.8% compared with 44.8%; p < 0.0001). GEn also significantly improved sleep outcomes (Post-Sleep Questionnaire, Pittsburgh Sleep Diary and Medical Outcomes Sleep Scale) compared with placebo. The most commonly reported adverse events were somnolence (GEn 1200 mg = 18.0%; 600 mg = 21.7%; placebo = 2.1%) and dizziness (GEn 1200 mg = 24.3%; 600 mg = 10.4%; placebo = 5.2%). Dizziness increased with increased dose and led to discontinuation in 2 subjects (GEn 1200 mg, n = 1; GEn 600 mg, n = 1). Somnolence led to discontinuation in 3 subjects (GEn 600 mg).
CONCLUSIONS
GEn 1200 mg and 600 mg significantly improve RLS symptoms and sleep disturbance compared with placebo and are generally well tolerated.
研究目的
评估加巴喷丁恩卡比（GEn）1200mg 或 600mg 与安慰剂相比在中重度原发性不安腿综合征（RLS）患者中的疗效和耐受性。
方法
这是一项为期 12 周、多中心、双盲、安慰剂对照的研究，将受试者（1:1:1）随机分配至 GEn 1200mg、600mg 或安慰剂组。主要终点：与安慰剂相比，GEn 1200mg 治疗组在第 12 周 LOCF 时的国际不安腿综合征量表（IRLS）总分的平均变化和研究者评定的临床总体印象-改善量表（CGI-I）的应答者比例（评为“非常”或“明显”改善）。次要终点包括 GEn 600mg 与安慰剂在第 12 周 LOCF 时的 IRLS 和 CGI-I 以及睡眠的主观测量。安全性和耐受性评估包括不良事件。
结果
325 名受试者被随机分配（GEn 1200mg = 113；600mg = 115；安慰剂 = 97）。与安慰剂相比，GEn 1200mg 显著改善了第 12 周 LOCF 时的 IRLS 总分（基线：23.2[5.32]；第 12 周：10.2[8.03]）（调整后的平均治疗差异 [AMTD]：-3.5；p = 0.0015），并且 GEn 1200mg 治疗的受试者（77.5%）明显多于安慰剂治疗的受试者（44.8%）对 CGI-I 有应答（p < 0.0001）。GEn 600mg 在 IRLS（AMTD：-4.3；p < 0.0001）和 CGI-I（72.8%与 44.8%；p < 0.0001）方面也观察到了类似的显著结果。GEn 还显著改善了睡眠结局（睡眠后问卷、匹兹堡睡眠日记和医疗结局睡眠量表）与安慰剂相比。最常见的不良事件是嗜睡（GEn 1200mg = 18.0%；600mg = 21.7%；安慰剂 = 2.1%）和头晕（GEn 1200mg = 24.3%；600mg = 10.4%；安慰剂 = 5.2%）。头晕随剂量增加而增加，导致 2 名受试者停药（GEn 1200mg，n = 1；GEn 600mg，n = 1）。3 名受试者因嗜睡而停药（GEn 600mg）。
结论
与安慰剂相比，GEn 1200mg 和 600mg 可显著改善 RLS 症状和睡眠障碍，且通常具有良好的耐受性。
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