MP24-17 PERVASIVE BIOFILM COVERAGE: AN ANALYSIS OF BIOFILM FORMATION IN INDWELLING URINARY CATHETERS

INTRODUCTION AND OBJECTIVES: AQX-1125 is a novel SH2-containing inositol-50-phosphatase 1 (SHIP1) activator previously demonstrated to modulate inflammation. Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic condition of unknown etiology, associated with inflammation of the bladder epithelium. The LEADERSHIP trial was a multicenter, randomized, double-blind, placebocontrolled, Phase 2 clinical trial investigating the ability of 200 mg AQX1125 to reduce pain in female patients with IC/BPS in North America. Here we assess the extent of bladder exposure to AQX-1125 over 6 weeks with trough drug levels in plasma and urine. METHODS: Blood and urine was collected after 28 and 42 days. Samples were analyzed for concentrations of AQX-1125 via HPLC-MS/MS methods and trough levels calculated. RESULTS: PK samples where collected from 35 patients randomized to AQX-1125. The mean/geometric mean plasma concentrations were 252/211 and 225/162 ng/mL for Days 28 and 42, respectively. The mean/geometric mean urine concentrations were 49,863/34,450 and 33,396/22,934 ng/mL for Days 28 and 42, respectively, at least 140-fold higher than the corresponding plasma levels. The trough plasma concentrations are similar to, or exceed, those anticipated for efficacy from earlier clinical trials and pre-clinical studies. CONCLUSIONS: The novel SHIP1 activator, AQX-1125 reaches the bladder of IC/BPS patients via both the bloodstream and the urine. The urinary route of elimination of AQX-1125 as parent compound may be an attractive property of the drug for IC/BPS. If once daily oral AQX-1125 proves effective in ameliorating symptoms of IC/BPS, both systemic and direct exposure of drug to the bladder may contribute to that response. This pharmacokinetic data supports continued development of AQX-1125 as an oral, once-daily therapy for IC/BPS.