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

被引:16
作者
Franco, Israel [1 ]
Hoebeke, Piet [2 ]
Bolong, David [3 ]
Davies, Leon N. [4 ]
Dahler, Ellen [5 ]
Snijder, Robert [6 ]
Stroosma, Otto [6 ]
Verheggen, Frank [6 ]
Newgreen, Donald [6 ]
Bosman, Brigitte [6 ]
Vande Walle, Johan [7 ]
机构
[1] Yale New Haven Med Ctr, Sect Pediat Urol, 20 York St, New Haven, CT 06504 USA
[2] Ghent Univ Hosp, Dept Pediat Urol, Ghent, Belgium
[3] Childrens Mem Hlth Inst, Dept Pediat Urol, Warsaw, Poland
[4] Philippine Childrens Med Ctr, Sect Pediat Nephrol, Manila, Philippines
[5] Aston Univ, Aston Optometry Sch, Birmingham, W Midlands, England
[6] Astellas Pharma Europe BV, Leiden, Netherlands
[7] Ghent Univ Hosp, Dept Pediat Nephrol, Ghent, Belgium
关键词
Children; Adolescents; Neurogenic; urinary bladder; Solifenacin; URINARY-TRACT FUNCTION; STANDARDIZATION COMMITTEE; BLADDER COMPLIANCE; CHILDREN; ADOLESCENTS; OXYBUTYNIN; TOLERABILITY; TERMINOLOGY;
D O I
10.1016/j.jpurol.2019.12.012
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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]
引用
收藏
页码:180.e1 / 180.e8
页数:8
相关论文
共 32 条
[1]   Solifenacin Is Effective and Well Tolerated in Patients With Neurogenic Detrusor Overactivity: Results From the Double-Blind, Randomized, Active- and Placebo-Controlled SONIC Urodynamic Study [J].
Amarenco, G. ;
Sutory, M. ;
Zachoval, R. ;
Agarwal, M. ;
Del Popolo, G. ;
Tretter, R. ;
Compion, G. ;
De Ridder, D. .
NEUROUROLOGY AND URODYNAMICS, 2017, 36 (02) :414-421
[2]  
[Anonymous], 2013, GUID CLIN INV MED PR
[3]  
[Anonymous], VESICARE 5MG FILM CO
[4]  
[Anonymous], TARG LIT REV NEUR DE
[5]  
[Anonymous], 2002, VITAL HLTH STAT
[6]   The Standardization of Terminology of Lower Urinary Tract Function in Children and Adolescents: Update Report from the Standardization Committee of the International Children's Continence Society [J].
Austin, Paul F. ;
Bauer, Stuart B. ;
Bower, Wendy ;
Chase, Janet ;
Franco, Israel ;
Hoebeke, Piet ;
Rittig, Soren ;
Walle, Johan Vande ;
von Gontard, Alexander ;
Wright, Anne ;
Yang, Stephen S. ;
Neveus, Tryggve .
JOURNAL OF UROLOGY, 2014, 191 (06) :1863-1865
[7]   Neurogenic bladder: etiology and assessment [J].
Bauer, Stuart B. .
PEDIATRIC NEPHROLOGY, 2008, 23 (04) :541-551
[8]   Efficacy and Adverse Events of Antimuscarinics for Treating Overactive Bladder: Network Meta-analyses [J].
Buser, Nora ;
Ivic, Sandra ;
Kessler, Thomas M. ;
Kessels, Alfons G. H. ;
Bachmann, Lucas M. .
EUROPEAN UROLOGY, 2012, 62 (06) :1040-1060
[9]   Efficacy and Safety of Transdermal and Oral Oxybutynin in Children With Neurogenic Detrusor Overactivity [J].
Cartwright, Patrick C. ;
Coplen, Douglas E. ;
Kogan, Barry A. ;
Volinn, Weining ;
Finan, Eileen ;
Hoel, Gary .
JOURNAL OF UROLOGY, 2009, 182 (04) :1548-1554
[10]   Treatment of Daytime Urinary Incontinence: A Standardization Document From the International Children's Continence Society [J].
Chang, Shang-Jen ;
Van Laecke, Erik ;
Bauer, Stuart B. ;
von Gontard, Alexander ;
Bagli, Darius ;
Bower, Wendy F. ;
Renson, Catherine ;
Kawauchi, Akihiro ;
Yang, Stephen Shei-Dei .
NEUROUROLOGY AND URODYNAMICS, 2017, 36 (01) :43-50