Emma Hitt, PhD

May 23, 2012

May 23, 2012 (Atlanta, Georgia) — In women with symptoms of overactive bladder (OAB), oral solabegron, a beta-3 adrenoreceptor agonist, significantly reduced incontinence episodes with no adverse events, according to findings from a randomized placebo-controlled double-blind phase 2 study.

Martin Michel, MD, PhD, from the Academic Medical Centre at the University of Amsterdam in the Netherlands, and colleagues presented the findings in an oral podium session here at the American Urological Association 2012 Annual Scientific Meeting.

Smooth muscle relaxation during bladder filling is mediated by beta-adrenergic receptors, predominantly of the beta-3 subtype in humans. Agonists of this receptor can be effective in the treatment of urinary frequency, urgency, and urgency incontinence. Solabegron is a highly selective high-affinity beta-3 adrenoceptor agonist currently in clinical development for the treatment of OAB symptoms.

In the study, 258 women with OAB symptoms (at least 8 micturitions, at least 1 incontinence episode, and at least 1 urgency episode per day) were randomized to receive solabegron 50 mg (n = 88), solabegron 125 mg (n = 85), or matching placebo (n = 85) twice daily for 8 weeks. The primary end point was change from baseline in the number of incontinence episodes per day.

Solabegron 125 mg significantly reduced the number of incontinence episodes from baseline, with a 65% adjusted mean reduction, a median reduction of 75%, and an adjusted mean difference from placebo of 21% (P = .025). At this dose, solabegron also significantly reduced the number of micturitions at week 4 (0.7; P = .05) and at week 8 (0.8; P = .036), and increased the volume voided per micturition at week 8 by 27% (P < .001).

No significant differences in adverse events were observed in the placebo and solabegron groups, with headache (8% vs 8%), nasopharyngitis (11% vs 6%), and dry mouth (4% vs 1%) being the most common events in the groups. No urinary retention or significant changes in clinical chemistry, hematology, or cardiac parameters were observed.

The response to solabegron was independent of the presence of the Trp64Arg polymorphism of the beta-3 adrenoceptor, the researchers note.

After 4 weeks of treatment, incontinence episodes were reduced in both the 50 mg (adjusted mean reduction, 23%; P = .03) and 125 mg (adjusted mean reduction, 32%; P = .003) solabegron groups, compared with placebo.

Dr. Michel explained that "the results of the phase 2 study demonstrate that solabegron is safe, well tolerated, and effective in the treatment of patients with OAB. "Beta-3-adrenoceptor agonists offer the promise of a safe and effective treatment for OAB patients," he said.

"This is the first clinical study on the potential use of solabegron in overactive bladder patients," Dr. Michel told Medscape Medical News. He added that muscarinic receptor antagonists are the current treatment for overactive bladder, but their use is limited by tolerability issues.

According to Dr. Michel, solabegron is expected to exhibit better tolerability than muscarinic receptor antagonists (e.g., it doesn't cause dry mouth). "The presently available clinical data do not yet allow us to determine whether it will also have better efficacy," he said.

Session moderator Ariana Smith, MD, assistant professor of urology in surgery at the Hospital of the University of Pennsylvania in Philadelphia, noted that it sounds like this drug has comparable efficacy to the antimuscarinics currently on the market. "There are perhaps fewer and less bothersome side effects also," she told Medscape Medical News in an interview, "and there appears to be a need and a role for this type of drug."

According to Dr. Smith, the next step will be a phase 3 trial to ensure that there are no problems, "specifically in men and women of reproductive potential and in patients with cardiovascular disease," she said. Dr. Smith added that it will be important to find out more about patient-reported outcomes, to "tell us if patients actually like the drugs."

"If the medicine is effective in reducing symptoms but patients don't refill their prescriptions, that tells us that they may not be comfortable with the side effects," she said. "This has yet to be determined with this drug."

The study was funded by GlaxoSmithKline Pharmaceuticals. Dr. Michel reports receiving research support and consultant and/or lecturer honoraria from Allergan, AltheRX, Astellas, Bayer, and Pfizer. After completion of the clinical solabegron study, he became an employee of Boehringer Ingelheim, a company that is not active in the overactive bladder field. Dr. Smith reports no relevant financial relationships.

American Urological Association (AUA) 2012 Annual Scientific Meeting: Abstract 520. Presented May 20, 2012.

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