Estrogen receptor beta agonist LY500307 fails to improve symptoms in men with enlarged prostate secondary to benign prostatic hypertrophy
Estrogen receptor beta agonist LY500307 fails to improve symptoms in men with enlarged prostate secondary to benign prostatic hypertrophy
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DOI：
10.1038/pcan.2014.43
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发表时间：
2015-03-01
影响因子：
4.8
通讯作者：
Jin, Y.
中科院分区：
文献类型：
--
作者：
Roehrborn, C. G.;Spann, M. E.;Jin, Y.
背景：评价选择性雌激素受体β激动剂LY500307治疗前列腺增生症患者下尿路症状(LUTS)的有效性和安全性。方法：采用随机、双盲、安慰剂对照、平行2期、疗效和安全性研究方法，将符合条件的中、重度下尿路症状患者随机分为安慰剂或LY500307，每日1、3、10、25 mg，每日1次，共24周。主要疗效终点为24周后国际前列腺症状总评分(IPSS)的变化。次要终点包括作为概念终点的前列腺总体积(TPV)的变化，以及IPSS生活质量、最大峰值尿流率(Qmax)、PSA和安全性(不良事件，实验室测试)。结果：根据先验定义的中期分析，共有414名患者因TPV减少不足而随机终止研究。IPSS从基线到终点的平均变化在安慰剂组为-3.4+/-6.8，在1、3、10和25 mg LY500307治疗组分别为-1.3+/-6.6、-2.6+/-7.0、-3.7+/-6.7和-4.4+/-5.7(P&gT；0.05)。同样，没有观察到任何次级疗效措施的治疗效果。不同治疗组的不良事件发生率相似，实验室检查没有观察到有临床意义的变化。结论：LY500307在BPH合并LUTS的患者中耐受性良好，每天一次，剂量25 mg，持续24周。由于疗效不佳，这项研究提前终止。
BACKGROUND: To assess the efficacy and safety of LY500307, a selective estrogen receptor beta agonist, on lower urinary tract symptoms (LUTS) in patients with enlarged prostate secondary to BPH.METHODS: In a randomized, double-blind, placebo-controlled, parallel phase 2, efficacy and safety study, eligible patients with moderate to severe LUTS and prostatic enlargement (>= 30 ml) were randomized to placebo or LY500307 at 1, 3, 10 and 25 mg once daily for 24 weeks. Primary efficacy end point was change in total International Prostate Symptoms Score (IPSS) after 24 weeks. Secondary end points included changes in total prostate volume (TPV) that served as a proof of concept end point, as well as IPSS quality of life, maximum peak urine flow rate (Qmax) and PSA and safety (adverse events, laboratory test).RESULTS: A total of 414 patients were randomized when the study was terminated because of insufficient TPV reduction, based on a priori defined interim analysis. The IPSS mean change from baseline to end point was -3.4 +/- 6.8 in the placebo group and -1.3 +/- 6.6, -2.6 +/- 7.0, -3.7 +/- 6.7 and -4.4 +/- 5.7 in the 1, 3, 10 and 25 mg LY500307-treated groups, respectively (P>0.05). Similarly, no treatment effect was observed for any of the secondary efficacy measures. Incidence of adverse events was comparable between treatment groups, and no clinically meaningful changes in laboratory tests were observed.CONCLUSIONS: LY500307 was well tolerated in BPH patients with LUTS at doses up to 25 mg once daily for 24 weeks. The study was terminated early because of inadequate efficacy.