AltheRx Pharmaceuticals, Malvern, PA 19355, USA.
Eur Urol. 2012 Nov;62(5):834-40. doi: 10.1016/j.eururo.2012.05.053. Epub 2012 Jun 5.
β-Adrenoceptor agonists are effective in animal models of bladder dysfunction, and the human bladder primarily expresses the β3 receptor subtype.
To evaluate the efficacy and tolerability of the highly selective and potent β3-adrenoceptor agonist solabegron in a clinical proof-of-concept study in incontinent women with overactive bladder (OAB).
DESIGN, SETTING, AND PARTICIPANTS: This was a randomized, double-blind trial in adult women with OAB (one or more 24-h incontinence episodes and eight or more average 24-h micturitions).
Solabegron 50 mg (n=88), solabegron 125 mg (n=85), or placebo (n=85)-all twice daily-were administered.
The primary efficacy end point was percentage change from baseline to week 8 in the number of incontinence episodes over 24 h. Secondary end points included actual change and percentage change from baseline to week 4 and week 8 in micturitions per 24 h, urgency episodes per 24 h, and volume voided per micturition. Adverse events (AEs) were assessed, as well.
Solabegron 125 mg produced a statistically significant difference in percent change from baseline to week 8 in incontinence episodes over 24h when compared with placebo (p=0.025). Solabegron 125 mg treatment also showed statistically significant reductions from baseline to weeks 4 and 8 in micturitions over 24 h and a statistically significant increase from baseline to week 8 in urine volume voided. Solabegron was well tolerated, with a similar incidence of AEs in each treatment group. There were no significant treatment differences for mean changes from baseline to week 8 in systolic blood pressure (BP), diastolic BP, mean arterial pressure (MAP), or heart rate during the 24-h ambulatory measurement.
Solabegron significantly reduced the symptoms of OAB in women with moderate to severe OAB. Solabegron was safe, well tolerated, and did not demonstrate significant differences in AEs as compared to placebo. β3-Adrenoceptor agonists may represent a new therapeutic approach for treating OAB symptoms.
β-肾上腺素受体激动剂在膀胱功能障碍的动物模型中具有疗效，而人类膀胱主要表达β3 受体亚型。
在一项以有急迫性尿失禁症状的膀胱过度活动症（OAB）成年女性为对象的临床概念验证研究中，评估高度选择性和强效β3-肾上腺素受体激动剂索利那新的疗效和耐受性。
设计、地点和参与者：这是一项在有 OAB（24 小时内至少有一次失禁发作，平均 24 小时内至少有 8 次排尿）的成年女性中进行的随机、双盲试验。
索利那新 50mg（n=88）、索利那新 125mg（n=85）或安慰剂（n=85），每日两次，均进行给药。
主要疗效终点为 24 小时内失禁发作次数自基线至第 8 周的百分比变化。次要结局终点包括自基线至第 4 周和第 8 周时 24 小时内排尿次数、急迫性发作次数以及每次排尿量的实际变化和百分比变化。还评估了不良事件（AE）。
与安慰剂相比，索利那新 125mg 治疗在 24 小时内失禁发作次数自基线至第 8 周的百分比变化方面具有统计学意义的差异（p=0.025）。索利那新 125mg 治疗还显示出自基线至第 4 周和第 8 周时 24 小时内排尿次数的统计学显著减少，以及自基线至第 8 周时每次排尿量的统计学显著增加。索利那新具有良好的耐受性，在每个治疗组中，AE 的发生率相似。在 24 小时动态血压测量期间，自基线至第 8 周的收缩压（BP）、舒张压、平均动脉压（MAP）或心率的平均变化与治疗无显著差异。
索利那新显著减轻了中重度 OAB 女性的 OAB 症状。与安慰剂相比，索利那新安全、耐受良好，且在 AE 方面无显著差异。β3-肾上腺素受体激动剂可能代表一种治疗 OAB 症状的新治疗方法。
