BACKGROUND: β-Adrenoceptor agonists are effective in animal models of bladder dysfunction, and the human bladder primarily expresses the β3 receptor subtype. OBJECTIVE: 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). INTERVENTIONS: Solabegron 50 mg (n=88), solabegron 125 mg (n=85), or placebo (n=85)-all twice daily-were administered. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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. RESULTS AND LIMITATIONS: 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. CONCLUSIONS: 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.
RCT Entities:
BACKGROUND: β-Adrenoceptor agonists are effective in animal models of bladder dysfunction, and the human bladder primarily expresses the β3 receptor subtype. OBJECTIVE: 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). INTERVENTIONS: Solabegron 50 mg (n=88), solabegron 125 mg (n=85), or placebo (n=85)-all twice daily-were administered. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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. RESULTS AND LIMITATIONS: 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. CONCLUSIONS: 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.
Authors: Hana Cernecka; Wisuit Pradidarcheep; Wouter H Lamers; Martina Schmidt; Martin C Michel Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2014-08-30 Impact factor: 3.000