PII-037 - FIH STUDY OF INTRAVENOUS RECCE327: A NOVEL, BROAD SPECTRUM, SYNTHETIC ANTI-INFECTIVE

A. Dunton¹, M. Dilizia², J. Ward², A. Carr², B. Koplowitz³, L. Pesco-Koplowitz³, M. Gillogly³, J. Prendergast⁴; ¹Danerius, LLC, ²RECCE Pharmaceuticals, Ltd, ³Duck Flats Pharma, ⁴RECCE Pharmaceuticals Ltd.

Background:

Background: RECCE327®(R327) is a synthetic/copolymer with a novel mechanism of action, being developed for treatment of resistant and ESKAPE bacterial infections, and sepsis. This study evaluated IV R327 safety, pharmacokinetics and pharmacodynamics.

Methods:

Methods: This was a randomized, double-blind, placebo-controlled, ascending-dose study in healthy male volunteers. 80 volunteers received a 1-hour infusion of R327 (50-6000mg) or placebo in 8 cohorts. Each cohort included up to 8 volunteers receiving R327 and 2 received placebo. Adverse event reporting, laboratories, ECG and telemetry were collected. Blood and urine samples were taken for determining plasma pharmacokinetics and urine concentrations. Ex vivo killing of Escherichia coli spiked urine samples containing R 327 were evaluated.

Results:

Results: There were no serious adverse events. Adverse events included mostly mild pain at the infusion site (superficial, peripheral arm vein) and some erythema at the higher doses most of which resolved at or near the completion of the infusion. Superficial vein thrombophlebitis was noted in R327 and placebo treated volunteers most notably in the higher dose groups. There were no clinically relevant changes in serum chemistry, hematology, coagulation, urinalysis, ECG or cardiac telemetry. Plasma pharmacokinetics revealed linear kinetics with mean tmax occurring at the end of the infusion and a median t1/2 of 1-2 hours which increased with dose. Urine concentrations were approximately 10-20X higher than plasma concentrations. Human urine spiked with E. coli and exposed to the minimum inhibitory concentration (MIC), 2X MIC and 5X MIC of R327 resulted in rapid (10 minutes or less) onset of bactericidal activity with the rate of the killing correlated with urine concentrations of R327.

Conclusion:

Conclusions: R327 was, in general, well-tolerated. Linear plasma pharmacokinetics were noted. Mean cohort urine concentrations were proportional to dose. R327 has a product profile suitable for its potential use in complicated or recurrent urinary tract infection as well as other serious infections. Moreover, it is noted that 30% of cases of sepsis are due to unresolved UTI infections. As such, R327 may be a significant new therapeutic modality for the treatment of sepsis.