The Efficacy and Safety of OnabotulinumtoxinA or Solifenacin Compared with Placebo in Solifenacin Naïve Patients with Refractory Overactive Bladder: Results from a Multicenter, Randomized, Double-Blind Phase 3b Trial.

PURPOSE: In this double-blind, randomized study we compared the efficacy and safety of onabotulinumtoxinA or solifenacin vs placebo in patients with overactive bladder who had urinary incontinence and an inadequate response to or were intolerant of an anticholinergic. Post hoc analysis was done to compare the effects of onabotulinumtoxinA vs solifenacin.

MATERIALS AND METHODS: Solifenacin naïve patients were randomized to onabotulinumtoxinA 100 U, solifenacin 5 mg, (which could escalate to 10 mg at week 6 according to predefined criteria) or placebo. Patients could request treatment 2 (open label onabotulinumtoxinA) after fulfilling prespecified criteria. End points included a change from baseline in the number of urinary incontinence episodes per day and the proportion of patients with a 100% reduction (dry) in the number of incontinence episodes per day as co-primaries, other urinary symptoms and quality of life, all at week 12, and adverse events.

RESULTS: The change from baseline in incontinence episodes per day was significantly greater with onabotulinumtoxinA or solifenacin vs placebo (-3.19 or -2.56, respectively, vs -1.33, both p <0.001). The incontinence reduction was significantly greater for onabotulinumtoxinA vs solifenacin (p = 0.022). At week 12, 33.8% (vs placebo p <0.001), 24.5% (vs placebo p = 0.028) and 11.7% of patients receiving onabotulinumtoxinA, solifenacin and placebo, respectively, were dry. After treatment 2, which was open label onabotulinumtoxinA, 43.2%, 37.6% and 41.9% of patients in the onabotulinumtoxinA, solifenacin and placebo groups, respectively, were dry. Significant improvements in other urinary symptoms and quality of life were observed for both active treatments. Urinary tract infection in 25.5% of cases and urinary retention in 6.9% were more common with onabotulinumtoxinA.

CONCLUSIONS: The efficacy of onabotulinumtoxinA and solifenacin was significantly higher than that of placebo. However, onabotulinumtoxinA showed significantly greater decreases in urinary incontinence than solifenacin with a third of patients achieving a 100% incontinence reduction. No unexpected safety signals were observed.