title: A Phase II Study of the Efficacy and Safety of the Novel Oral SHIP1 Activator AQX-1125 in Subjects with Moderate to Severe Interstitial Cystitis/Bladder Pain Syndrome.
abstract: OBJECTIVE
  In this 6-week, randomized, double-blind, placebo controlled, multicenter trial we assessed the effect of the novel SHIP1 (SH2-containing inositol-5'-phosphatase 1) activator AQX-1125 on bladder pain and urinary symptoms in patients with interstitial cystitis/bladder pain syndrome.
  
  
  METHODS
  Women with interstitial cystitis/bladder pain syndrome and a mean pain score of 5 or greater on an 11-point 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 (before visits) were recorded by e-diary and at clinic visits. The O'Leary-Sant ICSI (Interstitial Cystitis Symptom Index) and ICPI (Interstitial Cystitis Problem Index), BPIC-SS (Bladder Pain Interstitial Cystitis Symptom Score) and SF-12v2® questionnaires were administered. Safety was monitored through 6 weeks of treatment and 4 weeks of followup.
  
  
  RESULTS
  A total of 37 patients received oral AQX-1125 and 32 received placebo. At 6 weeks average daily pain on an e-diary decreased by 2.4 points for AQX-1125 vs 1.4 for placebo (p = 0.061), while average pain at clinic decreased by 2.6 vs 1.1 (p = 0.008), maximum daily pain on e-diary diary decreased by 2.6 vs 1.4 (p = 0.030) and maximum pain at clinic decreased by 2.8 vs 1.1 (p = 0.028). AQX-1125 reduced ICSI by 3.8 points vs 1.4 for placebo (p = 0.005), ICPI by 3.6 points 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 per 24 hours vs 0.8 for placebo (p = 0.040). Adverse event rates were similar for AQX-1125 and placebo (51.4% and 78.1%, respectively). No serious adverse events were reported.
  
  
  CONCLUSIONS
  Women with moderate to severe interstitial cystitis/bladder pain syndrome who were 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 interstitial cystitis/bladder pain syndrome. It warrants further investigation.
authors.affiliation: Queen's University, Kingston, Ontario, Canada. Electronic address: cn@queensu.ca.
authors.forename: J Curtis
authors.initials: JC
authors.lastname: Nickel
authors.affiliation: University of Western Ontario, London, Ontario, Canada.
authors.forename: Blair
authors.initials: B
authors.lastname: Egerdie
authors.affiliation: Citrus Valley Medical Centre, Glendora, California.
authors.forename: Edward
authors.initials: E
authors.lastname: Davis
authors.affiliation: Wake Forest University, Winston Salem, North Carolina.
authors.forename: Robert
authors.initials: R
authors.lastname: Evans
authors.affiliation: Aquinox Pharmaceuticals (Canada), Inc., Vancouver, British Columbia, Canada.
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mackenzie
authors.affiliation: Aquinox Pharmaceuticals (Canada), Inc., Vancouver, British Columbia, Canada.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Shrewsbury
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D003511:Cyclohexanols / Q000008:administration & dosage*; D018856:Cystitis, Interstitial / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D003558:Cystoscopy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D017699:Pelvic Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / Q000187:drug effects* / Q000378:metabolism; D012189:Retrospective Studies; D013577:Syndrome; D013997:Time Factors; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000000981:diagnostic imaging*; D055815:Young Adult
chemical_list: C582990:4-(4-(aminomethyl)-7a-methyl-1-methylideneoctahydro-1H-inden-5-yl)-3-(hydroxymethyl)-4-methylcyclohexan-1-ol; D003511:Cyclohexanols; D007189:Indans; C000606430:INPP5D protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
keywords: 4-(4-(aminomethyl)-7a-methyl-1-methylideneoctahydro-1H-inden-5-yl)-3-(hydroxymethyl)-4-methylcyclohexan-1-ol; cystitis, interstitial; pain; questionnaires; urinary bladder