NorLeu3-A(1-7) stimulation of diabetic foot ulcer healing: results of a randomized, parallel-group, double-blind, placebo-controlled phase 2 clinical trial.
NorLeu3-A(1-7) stimulation of diabetic foot ulcer healing: results of a randomized, parallel-group, double-blind, placebo-controlled phase 2 clinical trial.
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DOI：
10.1111/j.1524-475x.2012.00804.x
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
diZerega GS
中科院分区：
文献类型：
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作者：
Balingit PP;Armstrong DG;Reyzelman AM;Bolton L;Verco SJ;Rodgers KE;Nigh KA;diZerega GS
这项随机、双盲、安慰剂对照的2期临床试验探讨了NorLeu 3-A（DSC 127）在糖尿病足溃疡中的安全性和愈合疗效。对患有慢性、非感染、神经性或神经缺血性足底瓦格纳1级或2级足部溃疡的患者（n=172）进行不愈合筛选。受试者随机接受4周的0.03%DSC 127（n=26）、0.01%DSC 127（n=27）或安慰剂（n=24）每日一次局部治疗，随后接受20周的标准治疗。评估了DSC 127的安全性（包括实验室值和不良事件）、主要疗效（第12周时完全上皮化的溃疡%）和疗效持久性。比较了ITT组之间的基线、人口统计学和安全性参数，结果相当。对于ITT和PP人群，第12周（安慰剂组40%; 0.01%DSC 127组67%; 0.03%DSC 127组80%）和第24周（安慰剂组23%; 0.01%DSC 127组53%; 0.03%DSC 127组95%）DSC 127对面积较基线减少百分比影响的剂量-反应曲线均遵循对数线性模式。协变量分析比较了溃疡面积、深度和体积较基线的减少; 0.03%DSC 127组在第12周和第24周的减少更大。安慰剂治疗的溃疡愈合时间中位数为22周，而0.03%DSC 127治疗的溃疡愈合时间中位数为8.5周（p=0.04）。这项研究提供了初步证据，表明DSC 127在加速糖尿病足溃疡愈合方面是安全有效的。
This randomized, double-blind, placebo-controlled Phase 2 clinical trial explored NorLeu3-A (DSC127) safety and healing efficacy in diabetic foot ulcers. Patients with chronic, non-infected, neuropathic or neuroischemic plantar Wagner Grade 1 or 2 foot ulcers (n=172) were screened for non-healing. Subjects were randomized to receive four weeks’ once-daily topical treatment with 0.03%DSC127 (n=26), 0.01%DSC127 (n=27), or Placebo (n=24), followed by 20 weeks’ Standard of Care. DSC127 was assessed for safety (including laboratory values and Adverse Events), primary efficacy (% ulcers completely epithelialized at Week 12), and durability of effect. Baseline, demography, and safety parameters were compared between ITT groups and were comparable. Dose-response curves for DSC127 effect on % area reduction from baseline at Weeks 12 (40% Placebo; 67% 0.01%DSC127; 80% 0.03%DSC127) and 24 (23% Placebo; 53% 0.01%DSC127; 95% 0.03%DSC127) followed a log-linear pattern for both ITT and PP populations. Covariate analysis compared reduction in ulcer area, depth, and volume from baseline; reductions in the 0.03%DSC127 group were greater at Weeks 12 and 24. Placebo treated ulcers healed in a median 22 weeks vs. 8.5 weeks for 0.03%DSC127 (p=0.04). This study provides preliminary evidence that DSC127 is safe and effective in accelerating the healing of diabetic foot ulcers.