Queen's University, Kingston, Ontario, Canada.
University of Western Ontario, London, Ontario, Canada.
J Urol. 2016 Sep;196(3):747-54. doi: 10.1016/j.juro.2016.03.003. Epub 2016 Mar 9.
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.
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.
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.
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.
在这项为期 6 周、随机、双盲、安慰剂对照、多中心试验中，我们评估了新型 SHIP1（含 SH2 结构域的肌醇 5'-磷酸酶 1）激活剂 AQX-1125 对间质性膀胱炎/膀胱疼痛综合征患者膀胱疼痛和尿路症状的影响。
间质性膀胱炎/膀胱疼痛综合征患者，平均疼痛评分在 11 分制上为 5 或更高，尽管经过治疗，仍随机接受 AQX-1125 或安慰剂口服，每天一次，持续 6 周。通过电子日记和临床就诊记录平均和最大疼痛评分（每日）和尿频率（就诊前）。进行 O'Leary-Sant ICSI（间质性膀胱炎症状指数）和 ICPI（间质性膀胱炎问题指数）、BPIC-SS（膀胱疼痛间质性膀胱炎症状评分）和 SF-12v2®问卷。通过 6 周的治疗和 4 周的随访监测安全性。
共有 37 名患者接受了 AQX-1125 口服治疗，32 名患者接受了安慰剂治疗。6 周时，电子日记的平均每日疼痛评分，AQX-1125 组下降 2.4 分，安慰剂组下降 1.4 分（p=0.061），而临床就诊时的平均疼痛评分，AQX-1125 组下降 2.6 分，安慰剂组下降 1.1 分（p=0.008），电子日记的最大每日疼痛评分，AQX-1125 组下降 2.6 分，安慰剂组下降 1.4 分（p=0.030），临床就诊时的最大疼痛评分，AQX-1125 组下降 2.8 分，安慰剂组下降 1.1 分（p=0.028）。AQX-1125 使 ICSI 降低 3.8 分，安慰剂组降低 1.4 分（p=0.005），ICPI 降低 3.6 分，安慰剂组降低 1.6 分（p=0.014），BPIC-SS 降低 8.8 分，安慰剂组降低 4.0 分（p=0.011）。AQX-1125 组 24 小时排尿次数减少 3.6 次，安慰剂组减少 0.8 次（p=0.040）。AQX-1125 和安慰剂的不良事件发生率相似（分别为 51.4%和 78.1%）。没有严重的不良事件报告。
接受口服 SHIP1 激活剂 AQX-1125 治疗的中度至重度间质性膀胱炎/膀胱疼痛综合征女性患者报告膀胱疼痛显著减轻，尿路症状在 6 周时得到改善。AQX-1125 具有良好的耐受性。AQX-1125 可能是一种治疗间质性膀胱炎/膀胱疼痛综合征的潜在新疗法。值得进一步研究。
