NorLeu3-A(1-7) stimulation of diabetic foot ulcer healing: results of a randomized, parallel-group, double-blind, placebo-controlled phase 2 clinical trial.
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.
Olive View-UCLA Medical Center, University of California, Los Angeles, Sylmar, California, USA.
Peter P
PP
Balingit
David G
DG
Armstrong
Alexander M
AM
Reyzelman
Laura
L
Bolton
Shelagh J
SJ
Verco
Kathleen E
KE
Rodgers
Katherine A
KA
Nigh
Gere S
GS
diZerega
D000287:Administration, Topical; D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D017719:Diabetic Foot / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*
D043925:Angiogenesis Inducing Agents; D010446:Peptide Fragments; C473306:norLeu3-A(1-7); D000804:Angiotensin II