ORAL ZOPOLRESTAT IN SUBJECTS WITH PERIPHERAL SYMMETRICAL DIABETIC POLYNEUROPATHY

在长达3周的初始筛选期后，每位受试者将进入约4周的安慰剂单盲基线期，以进行基线评估。单盲安慰剂基线期之后将是18个月的双盲期，在此期间，每个受试者将接受安慰剂或唑来司他治疗。在双盲治疗期间，将获得完整的神经电生理评估。基线腓肠神经活检将在所有神经电生理评估后的第0周就诊时进行。最后一次腓肠神经活检将在第78周进行。主要疗效终点为腓肠神经纤维密度和复合神经电生理指标。完成整个78周治疗且无重大方案违规的受试者，以及完成所有最终疗效和安全性确定（包括最终腓肠神经活检）的受试者将自动被允许进入方案078-107x，这是当前方案的2年半延长，以收集关于佐来司他长期给药的额外安全性和有效性数据。

After an initial screening period of up to 3 weeks, each subjects will enter a single-blind placebo baseline period of approximately 4 weeks duration to perform baseline assessments. The single-blind placebo baseline period will be followed by a double-blind period of 18 months duration during which each subject will be treated with either placebo or zopolrestat. During double-blind therapy, complete neuroelectrophysiology evaluations will be obtained. A baseline sural nerve biopsy will be performed at the week 0 visit after all neuroelectrophysiology evaluations. The final sural nerve biopsy will be performed at week 78. Primary efficacy endpoints are sural nerve fiber density and composite neuroelectrophysiology. Subjects who have completed the entire 78 weeks of therapy without major protocol violations and who have had all final efficacy and safety determinations including hte final sural nerve biopsy will automatically be allowed to enter Protocol 078-107x, a 2 1/2 year extension of the current protocol to collect additional safety and efficacy data on longer-term administration of zopolrestat.