PolyMedix, Inc. (OTC BB: PYMX), an emerging biotechnology company focused on developing new therapeutic drugs to treat infectious diseases and acute cardiovascular disorders, today announced the successful completion of a Phase 1 exposure-escalation clinical study with its synthetic defensin-mimetic antibiotic, PMX-30063. The study results showed that PMX-30063 may be safely administered at a high dose for more than five days. These data support dosing levels being studied in the current Phase 2 efficacy study in Staph infections. The results also showed very similar pharmacokinetic profiles of PMX-30063 in male and female subjects.
This randomized, double-blind, placebo-controlled Phase 1 study enrolled twenty male and female subjects at a single site in the United States. Subjects randomized to PMX-30063 received an initial intravenous loading dose of PMX-30063 followed by a daily maintenance dose for up to 14 days. Pharmacokinetic sampling and other neurosensory tests were conducted during treatment and for 30-days thereafter. The doses of PMX-30063 administered were identical to the highest dose regimen currently being administered for five days in PolyMedix's Phase 2 clinical trial in patients with ABSSSI (Acute Bacterial Skin and Skin Structure Infections) caused by Staphylococcus bacteria, including MRSA.
Similar to results from two previously completed Phase 1 clinical studies with PMX-30063, the most frequently reported side effects included transient sensations of numbness and tingling affecting the lips, face, and fingers (called paraesthesia). These sensations did not worsen over the course of the study and resolved on their own without any treatment shortly after discontinuation of PMX-30063 administration. There were no significant clinical neurosensory abnormalities noted. Only one subject discontinued from the study due to paraesthesia. Several subjects were discontinued by the investigator after receiving between nine and thirteen days of dosing due to increased blood pressure and heart rate, for which there were no associated clinical signs or symptoms. After nine days of dosing, there was one reportable adverse event of atrial fibrillation that was fully reversed within a few hours following dosing. As seen in previous Phase 1 clinical studies, there were a few minor and transient increases in liver enzymes that were not clinically significant. All subjects demonstrated complete return to normal clinical parameters and reported no adverse effects by the time of the last follow up visit. There were no differences in the pharmacokinetics profiles between males and females.
To identify the mechanism of action for the paraesthesias observed in subjects receiving higher doses of PMX-30063, PolyMedix has conducted additional in vivo and in vitro studies. Results from these studies suggest that the paraesthesias may be related to temporary interactions with certain specific sodium, potassium, or acid sensing ion channels which are found on peripheral sensory nerve fibers.
"We are pleased with these Phase 1 results which show the safety of PMX-30063 at a high dose level and beyond five days of treatment," commented Dr. Bozena Korczak, Senior Vice President, Drug Development and Chief Development Officer of PolyMedix. "Our mechanistic studies now provide us with a better understanding of the processes underlying the sensory effects of PMX-30063, which is similar to that reported for a number of currently marketed drugs. We find this information, coupled with the pharmacokinetic data, to be encouraging and supportive of our clinical activities and plans for the development of PMX-30063. We look forward to the results from our ongoing Phase 2 efficacy trial in Staph infections."
Separate from the Phase 1 clinical study, PolyMedix has also conducted in vitro assays in which PMX-30063 has shown bactericidal activity against the NDM-1 drug-resistant strain of Klebsiella pneumonia. NDM-1 (New Delhi metallo-beta-lactamase-1) is an enzyme carried by some bacteria that confers resistance to many antibiotics, including carbapenems. PolyMedix has previously published results showing that PMX-30063 is bactericidal against 181 different drug-resistant and multi-drug resistant strains of Staphylococcus bacteria (different MRSA strains). These in vitro assays show that PMX-30063 is also active in killing the NDM-1 drug-resistant strain of Klebsiella pneumonia. The results showed no substantial differences between the effective concentrations for the NDM-1 and non-NDM-1 strains, indicating that the resistance mechanism associated with NDM-1 may not be effective against PMX-30063.
PolyMedix intends to conduct additional analysis on these data prior to submission for publication or presentation at future scientific meeting(s).
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