Assessment of maximum tolerated dose of a new herbal drug, Semelil (ANGIPARSTM) in patients with diabetic foot ulcer: A Phase I clinical trial


Abstract: Background and the purpose of the study: In many cases of diabetic foot ulcer (DFU) management, wound healing is incomplete, and wound closure and epithelial junctional integrity are rarely achieved. Our aim was to evaluate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of Semelil (ANGIPARSTM), a new herbal compound for wound treatment in a Phase I clinical trial. Methods: In this open label study, six male diabetic patients with a mean age of 57±7.6 years were treated with escalating intravenous doses of Semelil, which started at 2 cc/day to 13.5 cc/day for 28 days. Patients were assessed with a full physical exam; variables which analyzed included age, past history of diabetes and its duration, blood pressure, body temperature, weight, characteristics of DFU, Na, K, liver function test, Complete Blood Count and Differential(CBC & diff), serum amylase, HbA1c, PT, PTT, proteinuria, hematuria, and side effects were recorded. All the measurements were taken at the beginning of treatment, the end of week 2 and week 4. We also evaluated Semelil’s side effects at the end of weeks 4 and 8 after ending therapy. Results and major conclusions: Up to the drug dose of 10 cc/day foot ulcer dramatically improved. We did not observe any clinical or laboratory side effects at this or lower dose levels in diabetic patients. With daily dose of 13.5 cc of Semelil we observed phlebitis at the infusion site, which was the only side effect. Therefore, in this study we determined the MTD of Semelil at 10 cc/day, and the only DLT was phlebitis in injection vein. The recommended dose of Semelil I.V. administration for Phase II studies was 4 cc/day. Keywords: Semelil, ANGIPARS™, Diabetic foot ulcer, wound healing, Melilotus officinalis, Clinical Trial Phase I