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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

(2020) JOURNAL OF PEDIATRIC UROLOGY. 16(2). p.180.e1-180.e8
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Abstract
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 cm H2O), number of overactive detrusor contractions (>15 cm H2O), 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 systemerelated side-effects, and facial flushing. Conclusion Solifenacin was effective and well tolerated in pediatric patients with NDO, aged 6 monthse<18 years, suggesting that it is a viable alternative to oxybutynin, the current standard of care. [GRAPHICS]
Keywords
Pediatrics, Perinatology, and Child Health, Urology, Children, Adolescents, Neurogenic, urinary bladder, Solifenacin, BLADDER COMPLIANCE, CHILDREN, ADOLESCENTS, OXYBUTYNIN, STANDARDIZATION, TOLERABILITY

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MLA
Franco, Israel, et al. “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.” JOURNAL OF PEDIATRIC UROLOGY, vol. 16, no. 2, 2020, pp. 180.e1-180.e8, doi:10.1016/j.jpurol.2019.12.012.
APA
Franco, I., Hoebeke, P., Baka-Ostrowska, M., Bolong, D., Davies, L. N., Dahler, E., … Vande Walle, J. (2020). 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. JOURNAL OF PEDIATRIC UROLOGY, 16(2), 180.e1-180.e8. https://doi.org/10.1016/j.jpurol.2019.12.012
Chicago author-date
Franco, Israel, Piet Hoebeke, Małgorzata Baka-Ostrowska, David Bolong, Leon N. Davies, Ellen Dahler, Robert Snijder, et al. 2020. “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.” JOURNAL OF PEDIATRIC UROLOGY 16 (2): 180.e1-180.e8. https://doi.org/10.1016/j.jpurol.2019.12.012.
Chicago author-date (all authors)
Franco, Israel, Piet Hoebeke, Małgorzata Baka-Ostrowska, David Bolong, Leon N. Davies, Ellen Dahler, Robert Snijder, Otto Stroosma, Frank Verheggen, Donald Newgreen, Brigitte Bosman, and Johan Vande Walle. 2020. “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.” JOURNAL OF PEDIATRIC UROLOGY 16 (2): 180.e1-180.e8. doi:10.1016/j.jpurol.2019.12.012.
Vancouver
1.
Franco I, Hoebeke P, Baka-Ostrowska M, Bolong D, Davies LN, Dahler E, et al. 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. JOURNAL OF PEDIATRIC UROLOGY. 2020;16(2):180.e1-180.e8.
IEEE
[1]
I. Franco et al., “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,” JOURNAL OF PEDIATRIC UROLOGY, vol. 16, no. 2, pp. 180.e1-180.e8, 2020.
@article{8658295,
  abstract     = {{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 cm H2O), number of overactive detrusor contractions (>15 cm H2O), 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 systemerelated side-effects, and facial flushing.

Conclusion

Solifenacin was effective and well tolerated in pediatric patients with NDO, aged 6 monthse<18 years, suggesting that it is a viable alternative to oxybutynin, the current standard of care.

[GRAPHICS]}},
  author       = {{Franco, Israel and Hoebeke, Piet and Baka-Ostrowska, Małgorzata and Bolong, David and Davies, Leon N. and Dahler, Ellen and Snijder, Robert and Stroosma, Otto and Verheggen, Frank and Newgreen, Donald and Bosman, Brigitte and Vande Walle, Johan}},
  issn         = {{1477-5131}},
  journal      = {{JOURNAL OF PEDIATRIC UROLOGY}},
  keywords     = {{Pediatrics,Perinatology,and Child Health,Urology,Children,Adolescents,Neurogenic,urinary bladder,Solifenacin,BLADDER COMPLIANCE,CHILDREN,ADOLESCENTS,OXYBUTYNIN,STANDARDIZATION,TOLERABILITY}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{180.e1--180.e8}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1016/j.jpurol.2019.12.012}},
  volume       = {{16}},
  year         = {{2020}},
}

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