Data_Sheet_2_Efficacy and Safety of IncobotulinumtoxinA in the Treatment of Lower Limb Spasticity in Japanese Subjects.xlsx

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依波托尼毒素A（Xeomin®，Merz Pharmaceuticals GmbH；总剂量400U）对日本下肢（LL）卒中后痉挛患者疗效与安全性，采用改良Ashworth痉挛评分量表（MAS-PF）对足跖屈肌进行评估。研究方法：这是一项III期临床试验（Japic临床研究数据库编号CTI-153030，2015年10月7日），包括一个为期12周的双盲主要治疗期（MP），其中208名受试者被随机分配接受一次依波托尼毒素A 400U（n = 104）或安慰剂（n = 104）的注射周期，以及一个开放标签的扩展期（OLEX），招募了202名受试者，接受三个注射周期，每个周期持续10-14周（最后一个周期固定为12周）。评估了MP第4周及OLEX周期结束时的MAS-PF变化。结果：MAS-PF变化的曲线下面积在MP期间，与安慰剂相比，依波托尼毒素A显示出统计学上显著的差异（平均：−7.74 vs. −4.76；最小二乘法平均：−8.40 vs. −5.81 [p = 0.0041]）。在OLEX期间，从基线到研究结束时的MAS-PF平均变化显示出重复注射后的持续改善。未观察到依波托尼毒素A治疗的新安全性问题。无论OLEX期间注射周期的间隔长度如何，其疗效和安全性均保持一致。结论：本研究证实，注射用依波托尼毒素A（总剂量400U）是治疗日本下肢痉挛患者的有效且耐受性良好的药物，且可使用灵活的10-14周注射间隔进行注射。