PARIS, FRANCE (UroToday.com) - Solabegron, a novel beta-3 adrenoceptor agonist with high affinity and selectivity, is in clinical development for the treatment of patients with overactive bladder.
A Phase II multi-center, randomized, double-blind, placebo-controlled, parallel group study was performed to evaluate the safety and efficacy of oral solabegron in 258 women with OAB symptoms.
Subjects were enrolled to receive solabegron 50 mg, 125 mg, or matching placebo twice daily for 8 weeks. Based on a 3-day electronic diary, patients with≥8 micturitions/24 hr, and ≥1 incontinence episodes/24 hr and ≥1 urgency episodes /24 hr were randomized to double-blind treatment. Percent change from baseline to week 8 in the number of incontinence episodes over 24 hr was the primary endpoint.
In this patient population the mean baseline for incontinence episodes was 4.5 episodes/24hr. For the primary endpoint, Solabegron (125 mg) produced a statistical significant 65% mean reduction from baseline in incontinence episodes and an adjusted mean difference from placebo of 21% (p=0.025). The median reduction in incontinence episodes was 75% from baseline. Solabegron produced an adjusted mean reduction from placebo in incontinence episodes for both the 50 mg (23%; p=0.03) and 125 mg (32%; p=0.003) treatment groups after 4 weeks of treatment. At the 125 mg dose there was a significant reduction in the number of micturitions at week 4 (- 0.7;p= 0.05) and week 8 (-0.8; p=0.036). There was a marked and significant increase in the volume voided per micturition at week 8 for the solabegron 125mg treatment group (+27%; p<0.001).Patients with the Trp64Arg polymorphism of the beta-3 adrenoceptor did not show a decrease in response to Solabegron. Solabegron was safe and well-tolerated.
There were no significant differences in AEs between placebo and the Solabegron treatment groups. The most common AE’s across the placebo and treatment groups were headache (8%, 8%), nasopharingitis (11%, 6%) and dry mouth (4%, 1%), respectively. There were no significant changes in clinical chemistry, hematology or ECG parameters. Urinary retention was not observed. There were no significant treatment differences for mean changes in ambulatory SBP, DBP, MAP or heart rate during 24 hr measurement.
The results of this Phase 2 study demonstrate that Solabegron is safe, well-tolerated and efficacious in the treatment of patients with OAB.
Presented by EH Ohlstein,1 MC Michel,2 and A von Keitz,3 at the 2012 Genitourinary Cancers Symposium - February 2 - 4, 2012 - San Francisco Marriott Marquis - San Francisco, California
1AltheRx Pharmaceuticals, Malvern PA, USA, 2Dept. Pharmacology & Pharmacotherapy, University of Amsterdam, The Netherlands, 3Urology Practice , Marburg Germany