A multicenter, double-blind, randomized, placebo-controlled trial of the β3-adrenoceptor agonist solabegron for overactive bladder.
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).


METHODS
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).


METHODS
Solabegron 50 mg (n=88), solabegron 125 mg (n=85), or placebo (n=85)-all twice daily-were administered.


METHODS
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.


CONCLUSIONS
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.
AltheRx Pharmaceuticals, Malvern, PA 19355, USA. eliot@altherx.com
Eliot H
EH
Ohlstein
Alexander
A
von Keitz
Martin C
MC
Michel
D058667:Adrenergic beta-3 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000814:Aniline Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001118:Argentina; D001315:Australia; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D009520:New Zealand; D056910:Republic of Korea; D013019:South Africa; D013624:Taiwan; D013997:Time Factors; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000503:physiopathology; D014549:Urinary Incontinence / Q000188:drug therapy* / Q000503:physiopathology; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects; D055815:Young Adult
D058667:Adrenergic beta-3 Receptor Agonists; D000814:Aniline Compounds; D001565:Benzoates; D001713:Biphenyl Compounds; C523977:solabegron