MP24-16 PLASMA AND URINARY PHARMACOKINETICS OF A NOVEL, ORAL SHIP1 ACTIVATOR AQX-1125 IN FEMALE PATIENTS WITH INTERSTITIAL CYSTITIS

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I1 Apr 2016MP24-16 PLASMA AND URINARY PHARMACOKINETICS OF A NOVEL, ORAL SHIP1 ACTIVATOR AQX-1125 IN FEMALE PATIENTS WITH INTERSTITIAL CYSTITIS J. Curtis Nickel, Robert Evans, Patrick Tam, Judy Toews, Lloyd Mackenzie, Heidi Biagi, and Stephen Shrewsbury J. Curtis NickelJ. Curtis Nickel More articles by this author , Robert EvansRobert Evans More articles by this author , Patrick TamPatrick Tam More articles by this author , Judy ToewsJudy Toews More articles by this author , Lloyd MackenzieLloyd Mackenzie More articles by this author , Heidi BiagiHeidi Biagi More articles by this author , and Stephen ShrewsburyStephen Shrewsbury More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.772AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES AQX-1125 is a novel SH2-containing inositol-5′-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, placebo-controlled, Phase 2 clinical trial investigating the ability of 200 mg AQX-1125 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. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e276 Advertisement Copyright & Permissions© 2016MetricsAuthor Information J. Curtis Nickel More articles by this author Robert Evans More articles by this author Patrick Tam More articles by this author Judy Toews More articles by this author Lloyd Mackenzie More articles by this author Heidi Biagi More articles by this author Stephen Shrewsbury More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...