Long-term efficacy and safety of solifenacin in pediatric patients aged 6 months to 18 years with neurogenic detrusor overactivity: results from two phase 3 prospective open-label studies


Introduction The standard recommended treatment for neurogenic detrusor overactivity (NDO) is clean intermittent catheterization combined with an antimuscarinic agent. However, the adverse systemic side effects of oxybutynin, the most widely used agent, are of concern. Objective To evaluate the efficacy and safety of solifenacin in pediatric patients with NDO, aged 6 months–<5 years and 5–<18 years. Study design Two open-label, baseline-controlled, phase 3 studies were conducted in pediatric patients with NDO. Patients were treated with sequential doses of solifenacin oral suspension (pediatric equivalent doses 2.5–10 mg) for 12 weeks to determine each patient’s optimal dose, followed by a fixed dose ≥40-week treatment period. Primary efficacy endpoint was change from baseline in maximum cystometric capacity (MCC) after 24 weeks. Secondary endpoints included bladder compliance, bladder volume until first detrusor contraction (>15 cmH2O), number of overactive detrusor contractions (>15 cmH2O), maximum catheterized volume (MCV)/24 h and incontinence episodes/24 h. Safety parameters were treatment-emergent adverse events (TEAEs), serious adverse events, laboratory variables, vital signs, electrocardiograms, and ocular accommodation and cognitive function assessments. Results After 24 weeks, MCC had significantly increased compared with baseline in patients aged 6 months–<5 years and 5–<18 years (37.0 ml and 57.2 ml, respectively; P < 0.001; Fig.). Improvement was also observed after 52 weeks’ treatment. Significant changes were observed from baseline to week 24 in all secondary endpoints in both age groups: increase in bladder compliance, increase in bladder volume to first detrusor contraction as a percentage of expected bladder capacity, reduction in the number of overactive detrusor contractions, increase in MCV, and decreased incontinence episodes. TEAEs were mostly mild or moderate and there were no new drug-related TEAEs compared with adult studies. Age-related improvements were noted in ocular accommodation and cognitive function. Discussion These long-term multicenter investigations demonstrated the efficacy and safety of solifenacin in pediatric patients with NDO. The observed increases in MCC were clinically relevant and demonstrated that an increase in fluid volume can be accommodated in the bladder prior to reaching intravesical pressures that endanger kidney function and/or are associated with leakage or discomfort. Solifenacin was well tolerated with low incidences of constipation and dry mouth (typically associated with antimuscarinics), central nervous system-related side effects and facial flushing. Conclusion Solifenacin was effective and well tolerated in pediatric patients with NDO, aged 6 months–<18 years, suggesting that it is a viable alternative to oxybutynin, the current standard of care.

Publication DOI: https://doi.org/10.1016/j.jpurol.2019.12.012
Divisions: College of Health & Life Sciences > School of Optometry > Optometry
College of Health & Life Sciences > School of Optometry > Optometry & Vision Science Research Group (OVSRG)
College of Health & Life Sciences > School of Optometry > Vision, Hearing and Language
College of Health & Life Sciences
Additional Information: © 2020 The Authors. Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/. Funding: Astellas Pharma Europe B.V.
Uncontrolled Keywords: Adolescents,Children,Neurogenic urinary bladder,Solifenacin,Pediatrics, Perinatology, and Child Health,Urology
Publication ISSN: 1477-5131
Last Modified: 01 Apr 2024 07:38
Date Deposited: 19 Dec 2019 08:25
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Related URLs: https://www.sci ... 47751311930436X (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2020-04-01
Published Online Date: 2019-12-27
Accepted Date: 2019-12-18
Authors: Franco, Israel
Hoebeke, Piet
Baka-Ostrowska, Małgorzata
Bolong, David
Davies, Leon (ORCID Profile 0000-0002-1554-0566)
Dahler, Ellen
Snijder, Robert
Stroosma, Otto
Verheggen, Frank
Newgreen, Donald
Bosman, Brigitte
Vande Walle, Johan

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