NorLeu3-A(1-7) stimulation of diabetic foot ulcer healing: results of a randomized, parallel-group, double-blind, placebo-controlled phase 2 clinical trial.

Abstract

This randomized, double-blind, placebo-controlled Phase 2 clinical trial explored NorLeu(3)-A(1-7) (DSC127) safety and healing efficacy in diabetic foot ulcers. Patients with chronic, noninfected, neuropathic, or neuroischemic plantar Wagner Grade 1 or 2 foot ulcers (n = 172) were screened for nonhealing. Subjects were randomized to receive 4 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 intent-to-treat groups and were comparable. Dose-response curves for DSC127 effect on % area reduction from baseline at Week 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 intent-to-treat and per-protocol 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.

• Authors: Peter P Balingit, David G Armstrong, Alexander M Reyzelman, Laura Bolton, Shelagh J Verco, Kathleen E Rodgers, Katherine A Nigh, Gere S diZerega
• Journal: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society (Wound Repair Regen) 2012 Jul-Aug Vol. 20 Issue 4 Pg. 482-90 ISSN: 1524-475X [Electronic] United States
• PMID: 22672145 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 by the Wound Healing Society.

Chemical References

• Angiogenesis Inducing Agents
• Peptide Fragments
• norLeu3-A(1-7)
• Angiotensin II

Topics

• Administration, Topical
• Angiogenesis Inducing Agents (administration & dosage, pharmacology)
• Angiotensin II (administration & dosage, pharmacology)
• Diabetes Mellitus, Type 1 (complications)
• Diabetes Mellitus, Type 2 (complications)
• Diabetic Foot (drug therapy, pathology, physiopathology)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Peptide Fragments (administration & dosage, pharmacology)
• Treatment Outcome
• Wound Healing (drug effects)