Solifenacin in Children and Adolescents with Overactive Bladder: Results of a Phase 3 Randomised Clinical Trial

Abstract

BackgroundSolifenacin, an effective, well-tolerated treatment for adult overactive bladder (OAB) symptoms, has not been evaluated in placebo-controlled paediatric clinical trials. ObjectivesTo evaluate the efficacy and safety of once-daily oral solifenacin suspension in OAB patients aged 5–<12 yr (children) and 12–<18 yr (adolescents). Design, setting, and participantsThe study involved a 4-wk urotherapy run-in followed by 1:1 randomisation to 12-wk double-blind solifenacin or placebo treatment alongside urotherapy. InterventionSolifenacin paediatric equivalent doses (PEDs) of adult doses: 2.5mg, 5mg, 7.5mg, and 10mg. The starting dose was PED 5mg; all patients were titrated to an optimum dose at 3-wk intervals over 9 wk, resulting in ≥3 wk at the optimum dose before end of treatment (EoT). Outcome measurements and statisticsSuperiority of solifenacin versus placebo in change from baseline to EoT for mean volume voided/micturition (MVV, primary endpoint); daytime maximum volume voided/micturition (DMaxVV); incontinence episodes (mean/24h); mean number of incontinence-free days or nights/7 d; micturition frequency; and Micturition frequency adjusted for baseline total voided volume (VTB) as an exploratory parameter). Efficacy parameters were analysed using analysis of covariance. Safety parameters (treatment-emergent adverse events, serious adverse events, laboratory variables, vital signs, electrocardiogram, postvoid residual volume) are summarised using descriptive statistics. Results and limitationsIn children, solifenacin was superior to placebo in terms of the change from baseline to EoT for MVV (solifenacin-placebo difference 12.1ml, 95% confidence interval [CI] 0.2–24.0; p=0.046), DMaxVV (difference in adjusted mean change from baseline for solifenacin–placebo 31.9ml, 95% CI 4.3–59.5; p=0.024), VTB-adjusted micturition frequency (p=0.028). Other endpoints were not significantly different. Solifenacin was well tolerated. For adolescents, it was not possible to draw firm efficacy conclusions because of the low numbers recruited. ConclusionsOnce-daily solifenacin oral suspension in children with OAB was superior to placebo for MVV (primary efficacy endpoint) and was well tolerated. Patient summaryIn this 12-wk study, a once-daily oral suspension of solifenacin in children aged 5–<12 yr with overactive bladder was superior to placebo in increasing mean volume voided/micturition, the primary efficacy variable in the study. Solifenacin was well tolerated, with a low incidence of dry mouth and constipation.This study is registered at ClinicalTrials.gov as NCT01565707.