A phase II dose-ranging study of mirabegron in patients with overactive bladder.
A phase II dose-ranging study of mirabegron in patients with overactive bladder.
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DOI：
10.1007/s00192-013-2042-x
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发表时间：
2013-09
影响因子：
1.8
通讯作者：
Yamaguchi, Osamu
中科院分区：
文献类型：
--
作者：
Chapple, Christopher R.;Dvorak, Vladimir;Radziszewski, Pjotr;Van Kerrebroeck, Philip;Wyndaele, Jean Jacques;Bosman, Brigitte;Boerrigter, Peter;Drogendijk, Ted;Ridder, Arwin;Van der Putten-Slob, Ingrid;Yamaguchi, Osamu
米拉贝格隆是一种有效和选择性的β3-肾上腺素能受体激动剂，对于膀胱过度活动症患者来说，它可能是一种替代抗肌松药的治疗选择。患者完成了为期2周的单盲安慰剂磨合期，然后使用米雷贝格隆口服控制吸收系统( = )25、50、100或200 mg每日一次(Qd)、安慰剂或托特罗定缓释剂(ER)4 mg qd进行为期12周的随机(N OCAS928)双盲治疗。主要终点是平均排尿次数/24小时从基线到治疗结束的变化。次要终点包括每次排尿的平均容量的变化；平均尿失禁、尿失禁和尿失禁发作的平均次数；24小时尿失禁的严重程度；夜间排尿；以及生活质量测量。安全性参数包括生命体征、不良事件、实验室检查、心电图测量和术后残气量。米拉贝格隆25、50、100和200毫克可剂量依赖性地减少(改善)治疗前至治疗结束时的尿频，分别为1.9、2.1、2.1和2.2尿频/24小时，而安慰剂组为1.4尿量/24小时(与米拉贝隆50、100和200毫克比较，p ≤ 0.05)。与安慰剂相比，服用米拉贝格隆的大多数次要终点包括生活质量变量在统计学上都有显着改善。虽然服用米拉贝格隆100毫克和200毫克组的脉搏频率较基线有显著增加(p <； 0.05)，但这与心血管不良事件发生率的增加无关。米拉贝格隆在这项II期剂量发现研究中的良好疗效和耐受性使其成功地进入了III期临床开发计划。
Mirabegron is a potent and selective β3-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder. Patients completed a single-blinded, 2-week placebo run-in period followed by 12 weeks of randomized (n = 928) double-blinded treatment with mirabegron oral controlled absorption system (OCAS) 25, 50, 100, or 200 mg once-daily (QD), placebo or tolterodine extended release (ER) 4 mg QD. The primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes/24 h. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes/24 h; severity of urgency; nocturia; and quality of life measures. Safety parameters included vital signs, adverse events, laboratory tests, electrocardiogram measurements and post-void residual volume. Mirabegron 25, 50, 100, and 200 mg resulted in dose-dependent reductions (improvements) from baseline to end-of-treatment in micturition frequency of 1.9, 2.1, 2.1, and 2.2 micturitions/24 h respectively, versus 1.4 micturitions/24 h with placebo (p ≤ 0.05 for the mirabegron 50-, 100-, and 200-mg comparisons). There was a statistically significant improvement with mirabegron compared with placebo for most secondary endpoints including quality of life variables. While there was a significant (p < 0.05) increase from baseline in pulse rate in the mirabegron 100-mg and 200-mg groups, this was not associated with an increased incidence of cardiovascular adverse events. The favorable efficacy and tolerability of mirabegron in this phase II dose-finding study has led to its successful advancement into a phase III clinical development program.
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影响因子：
2
作者：
通讯作者：
--
影响因子：
7.3
作者：
Igawa, Y;Yamazaki, Z;Andersson, KE
通讯作者：
Andersson, KE
影响因子：
3.5
作者：
Coyne, K;Revicki, D;Abrams, P
通讯作者：
Abrams, P
DOI：
10.1046/j.1464-410x.1996.93013.x
发表时间：
1996-04-01
期刊：
BRITISH JOURNAL OF UROLOGY
影响因子：
--
作者：
Donovan, JL;Abrams, P;Kondo, A
通讯作者：
Kondo, A
影响因子：
4.5
作者：
Andersson, Karl-Erik;Sarawate, Chaitanya;Kulkarni, Amit S.
通讯作者：
Kulkarni, Amit S.