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Medicine: Evidence-Based Research: Plenary Session
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Abstract This session will present new evidence-based data from recently performed clinical trails to be chosen before the meeting. (Presentation 23.4) Talactoferrin gel may promote healing of diabetic neuropathic ulcers Ernest W. Yankee, Michael Miller, Thomas Serena, Peter Sheehan, Lawrence Lavery, Robert Kirsner, Amber Reese, Aristidis Veves Talactoferrin alfa (TLF, previously known as recombinant human lactoferrin or rhLF) is a novel immunomodulatory protein with ulcer healing properties in animal models. A pilot phase 1/2 clinical study was conducted at 7 clinical sites to determine if this promising effect could also be shown in diabetic patients. Fifty-five patients with diabetic neuropathic foot ulcers participated in this 2-part study. In Part 1, groups of 3 patients each received 1%, 2.5%, or 8.5% talactoferrin gel in a sequential design, with twice-daily ulcer administration for 30 days. No drug-related adverse events (AEs) were found. Part 2 of the study was a 3-arm, randomized, placebo-controlled study of 2.5% and 8.5% gels. In combination with good wound care, the gels were administered twice daily onto a target ulcer for 12 weeks. The primary endpoint was the incidence of 75% healing at the end of dosing relative to baseline. Secondary endpoints included incidence of healing at different time points, time to complete ulcer closure, and rate of closure. The study, which was powered to detect a difference between the placebo and combined TLF arms with a P <0.1, met the primary objective. The groups receiving the 2.5% (n=15) and 8.5% (n=15) gels had double the incidence of 75% healing compared to the placebo group (n=16): 47%, 53%, and 25%, respectively. On an ITT basis, the combination of the two active groups when compared to the placebo group showed a strong trend toward statistical significance (P =0.09). This trend was also evident for 100% healing, 8 weeks following the end of therapy. There were no TLF-related AEs or laboratory abnormalities. Thus, topical rhLF appears to be an effective, safe, and well-tolerated drug that may enhance the rate of healing of diabetic neuropathic ulcers. References Wang Y, Talactoferrin Clinical Team, Yankee E, Varadhachary A. Double blind, placebo controlled trial of oral talactoferrin in combination therapy for first-line non-small cell lung cancer (NSCLC). Presented at ASCO, 2005. Berd D, Mastrangelo MJ, Bloome E, Jonas JM, Yankee EW. Long-term survival of high-risk melanoma patients following treatment with autologous, DNP-modified vaccine. Presented at the Clinical Oncology Society of Australia, Inc., 26th Annual Scientific Meeting, November 24–26, 1999. Yankee EW, Behzadi K, Doak K, Jonas JM, Berd D, Jimenez FA. Regulatory requirements for the characterization of a hapten-modified autologous tumor vaccine. FDA-NCI Workshop on Tumor Vaccines. December 10–11, 1998. Hsi RSP, Yankee EW, Stolle WT. Synthesis of tritium labeled arbaprostil and related 15-methyl prostaglandins. J Labelled Compounds Radiopharmaceuticals, XXV. 1987;(8):865–878. Robert A, Yankee EW. Gastric antisecretory effect of 15(R)-15-methyl PGE2, methyl ester and of 15(S)-15-methyl-PGE2, methyl ester. Proc Soc Exp Biol Med. 1975:148:1155–1158. Yankee EW, Axen U, Bundy GL. Total synthesis of 15-methylprostaglandins. J Amer Chem Soc. 1974;96:5865–5876. Yankee EW, Spencer B, Howe NE, Cram DJ. Stereochemistry. XLIV. Nucleophilic substitution at carbon with carbon as leaving group. J Amer Chem Soc. 1973;95:4220–4230. Yankee EW, Lin CH, Fried J. General method for the conversion of F into E prostaglandins. J Chem Soc Chem Commun. 1972;1120–1121. |
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