Solifenacin in Children and Adolescents with Overactive Bladder: Results of a Phase 3 Randomised Clinical Trial.
Solifenacin, an effective, well-tolerated treatment for adult overactive bladder (OAB) symptoms, has not been evaluated in placebo-controlled paediatric clinical trials.



To evaluate the efficacy and safety of once-daily oral solifenacin suspension in OAB patients aged 5-<12 yr (children) and 12-<18 yr (adolescents).



The study involved a 4-wk urotherapy run-in followed by 1:1 randomisation to 12-wk double-blind solifenacin or placebo treatment alongside urotherapy.



Solifenacin 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).



Superiority 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.



In 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.



Once-daily solifenacin oral suspension in children with OAB was superior to placebo for MVV (primary efficacy endpoint) and was well tolerated.



In 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.
Astellas Pharma Europe BV, Leiden, The Netherlands. Electronic address: donald.newgreen@astellas.com.
Donald
D
Newgreen
Astellas Pharma Europe BV, Leiden, The Netherlands.
Brigitte
B
Bosman
Astellas Pharma Europe BV, Leiden, The Netherlands.
Adriana
A
Hollestein-Havelaar
Astellas Pharma Europe BV, Leiden, The Netherlands.
Ellen
E
Dahler
Astellas Pharma Europe BV, Leiden, The Netherlands.
Robin
R
Besuyen
Astellas Pharma Europe BV, Leiden, The Netherlands.
Will
W
Sawyer
CHU de Québec, Division of Urology, Québec, Canada.
Stéphane
S
Bolduc
Aarhus University Hospital, Department of Paediatrics, Aarhus, Denmark.
Søren
S
Rittig
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003248:Constipation / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D000069464:Solifenacin Succinate / Q000627:therapeutic use*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000150:complications / Q000188:drug therapy*; D014549:Urinary Incontinence / Q000188:drug therapy* / Q000209:etiology; D014987:Xerostomia / Q000139:chemically induced
D018727:Muscarinic Antagonists; D000069464:Solifenacin Succinate
Adolescents; Children; Incontinence; Overactive bladder; Solifenacin