A Phase II Study of Efficacy and Safety of a Novel, Oral SHIP1 Activator, AQX-1125, in Subjects with Moderate to Severe Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS)

PURPOSE - This 6-week, randomized, double-blind, placebo-controlled, multi-center trial assessed a novel SH2-containing inositol-5'-phosphatase 1 (SHIP1) activator, AQX-1125, on bladder pain and urinary symptoms in IC/BPS.

METHODS - Women with IC/BPS and mean pain of ≥5 (11-pt scale) despite treatment were randomized to AQX-1125 or placebo, orally once daily for 6 weeks. Average and maximum pain scores (daily) and urinary frequency (pre-visits) were recorded by e-diary and at clinic visits. O'Leary-Sant Interstitial Cystitis Symptom (ICSI) and Problem Indices (ICPI), Bladder Pain Interstitial Cystitis Symptom Score (BPIC-SS) and Short-Form 12 Health Survey (SF-12v2) questionnaires were administered. Safety was monitored through 6 weeks treatment and 4 weeks follow-up.

RESULTS - 37 patients received oral AQX-1125 and 32 received placebo. At 6 weeks, average daily pain (e-diary) decreased by 2.4 points (AQX-1125) versus 1.4 (placebo) (p=0.061); average pain (clinic) by 2.6 vs 1.1 (p=0.008); maximum daily pain (e-diary) by 2.6 vs 1.4 (p=0.030) and maximum pain (clinic) by 2.8 vs 1.1 (p=0.028). AQX-1125 reduced ICSI by 3.8 points vs 1.4 (placebo) (p=0.005), ICPI by 3.6 vs 1.6 (p=0.014) and BPIC-SS by 8.8 points vs 4.0 (p=0.011). Urinary frequency decreased on AQX-1125 by 3.6 voids/24 hours vs 0.8 (placebo) (p=0.040). Adverse event rates were similar between AQX-1125 (51.4%) and placebo (78.1%). No SAEs reported.

CONCLUSIONS - Women with moderate to severe IC/BPS, treated with the oral SHIP1 activator, AQX-1125, reported significantly reduced bladder pain and improved urinary symptoms at 6 weeks. AQX-1125 was well tolerated. AQX-1125 may be a potential new treatment for IC/BPS, and warrants further investigation.

The Journal of urology. 2016 Mar 08 [Epub ahead of print]

J Curtis Nickel, Blair Egerdie, Edward Davis, Rober Evans, Lloyd Mackenzie, Stephen B Shrewsbury

Queen's University, Kingston, ON., University of Western Ontario, London, ON., Citrus Valley Medical Centre, Glendora, CA., Wake Forest University, Winston Salem, NC., Aquinox Pharmaceuticals (Canada) Inc, Vancouver, BC., Aquinox Pharmaceuticals (Canada) Inc, Vancouver, BC.