Data_Sheet_1_Efficacy and Safety of IncobotulinumtoxinA in the Treatment of Lower Limb Spasticity in Japanese Subjects.docx

ObjectiveTo confirm the efficacy and safety of incobotulinumtoxinA (Xeomin®, Merz Pharmaceuticals GmbH; total dose 400 U) in Japanese subjects with lower limb (LL) poststroke spasticity using the Modified Ashworth Scale spasticity score for the plantar flexors (MAS-PF).MethodsThis phase III study (Japic clinical study database No. CTI-153030, 7 October 2015) included a double-blind, 12-week main period (MP) in which 208 subjects were randomized to receive one injection cycle of incobotulinumtoxinA 400 U (n = 104) or placebo (n = 104) in the pes equinus muscles, and an open-label extension (OLEX) that enrolled 202 subjects who received three injection cycles, 10–14 weeks in duration (the last cycle was fixed at 12 weeks). Changes in MAS-PF for incobotulinumtoxinA vs. placebo from baseline to Week 4 of the MP and to the end-of-cycle visits in the OLEX were evaluated.ResultsThe area under the curve for the change in MAS-PF was statistically significantly greater with incobotulinumtoxinA vs. placebo in the MP (mean: −7.74 vs. −4.76; least squares mean: −8.40 vs. −5.81 [p = 0.0041]). In the OLEX, mean changes in MAS-PF from baseline to end-of-study showed continued improvement with repeated injections. No new safety concerns were observed with the incobotulinumtoxinA treatment. Its efficacy and safety were consistent regardless of the length of the injection cycle interval in the OLEX.ConclusionThis study demonstrated that incobotulinumtoxinA (total dose 400 U) is an effective and a well-tolerated treatment for LL spasticity in Japanese subjects using flexible injection intervals of 10–14 weeks.

本研究旨在验证注射用肉毒毒素A（Xeomin®，Merz Pharmaceuticals GmbH；总剂量为400U）对日本下肢（LL）中风后痉挛患者的疗效与安全性，评估指标为改良Ashworth量表（MAS）足跖屈肌痉挛评分。研究方法为III期临床试验（Japic临床研究数据库编号CTI-153030，2015年10月7日），包括为期12周的双盲主要治疗期（MP），期间208名受试者随机分配接受一次注射周期的注射用肉毒毒素A 400U（n = 104）或安慰剂（n = 104）于跟腱肌肉，以及开放标签的延长期（OLEX），该期招募了202名接受三次注射周期的受试者，注射周期持续10-14周（最后一个周期固定为12周）。评估了注射用肉毒毒素A与安慰剂在MP基线至第4周及OLEX周期结束时的MAS-PF变化曲线下面积。结果发现，在MP中，注射用肉毒毒素A组的MAS-PF变化曲线下面积与安慰剂组相比具有统计学上的显著差异（均值：-7.74 vs. -4.76；最小二乘均值：-8.40 vs. -5.81 [p = 0.0041]）。在OLEX中，从基线至研究结束时的MAS-PF均值变化显示，重复注射后继续改善。注射用肉毒毒素A治疗过程中未观察到新的安全性问题。其疗效与安全性不受OLEX注射周期间隔长度的影响。结论：本研究证实，注射用肉毒毒素A（总剂量400U）是针对日本下肢痉挛患者的一种有效且耐受性良好的治疗手段，采用10-14周的灵活注射间隔。