A Phase 3, Open-Label, Baseline-controlled, Multi-center, Sequential Dose-Titration Study to Assess the Pharmacokinetics, Long-Term Efficacy and Safety of Solifenacin Succinate Suspension in Children From 6 Months to Less Than 5 Years of Age With Neurogenic Detrusor Overactivity
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 8
- 主要终点
- Change From Baseline to Week 24 in Maximum Cystometric Capacity (MCC)
研究概览
简要总结
The purpose of this study was to evaluate long term efficacy and safety of treatment with solifenacin succinate (the study drug) in children with neurogenic detrusor overactivity after multiple dose administration.
详细描述
In some children with a severe form of spina bifida (which is the consequence of a spinal cord defect), the bladder muscle (detrusor) contracts strongly and without warning (also known as neurogenic detrusor overactivity) and the urethra (the passage connecting the bladder with outside) does not relax. Though these children cannot void, urine leakage can happen when the overactive contractions are strong, and/or the pressure in the bladder is so high that it overcomes the closed urethra (overflow at high filling bladder pressure). This high bladder pressure puts these children at risk for kidney damage and can decrease the quality of the bladder. Therapy was aimed to decrease the high filling bladder pressure and the overactive detrusor contractions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 4 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Myelomeningocoele
- •Documented diagnosis of NDO, confirmed by urodynamics
- •DSD (detrusor sphincter dyssynergia)
- •Practicing clean intermittent catheterization (CIC)
排除标准
- •Know genitourinary condition (other than NDO) that may cause incontinence
- •Bladder augmentation surgery
- •Current faecal impaction
- •Electro-stimulation therapy within 2 weeks prior to visit
- •Subjects with the following gastro-intestinal problems: partial or complete obstructions, decreased motility like paralytic ileus, subjects at risk of gastric retention
- •Reflux grade 3 to 5
- •Current urinary tract infection
研究组 & 干预措施
Solifenacin succinate
Children aged 6 months to less than 5 years were treated with sequential titrated doses of solifenacin up to 12 weeks in the Titration period after which a fixed dose of solifenacin was given for at least 40 weeks in the Fixed-dose assessment period. Children received solifenacin once daily during these 2 periods.
干预措施: Solifenacin succinate (Drug)
结局指标
主要结局
Change From Baseline to Week 24 in Maximum Cystometric Capacity (MCC)
时间窗: Baseline and Week 24
MCC was the volume instilled into the bladder prior to leakage or end of bladder-filling (whichever was reached first), as assessed by urodynamics (procedure: the bladder was to be filled until voiding/leakage began, or until it was stopped because either the participant experienced pain or discomfort or 135% of expected bladder capacity \[EBC\] was reached for participants ≥ 2 years or of maximum catheterized volume \[MCV\] for participants aged 6 months to \< 2 years; the participants' bladder was emptied via catheterization).
次要结局
- Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume at 10 cmH20 Detrusor Pressure(Baseline and Weeks 3, 6, 9, 12, 24, 52)
- Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume at 30 cmH20 Detrusor Pressure(Baseline and Weeks 3, 6, 9, 12, 24, 52)
- Change From Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Average First Morning Catheterized Volume(Baseline and Weeks 3, 6, 9, 12, 24, 36, 52)
- Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 12(3 days prior to Week 12 visit)
- Change From Baseline to Weeks 3, 6, 9, 12 and 52 in MCC(Baseline and Weeks 3, 6, 9, 12, 52)
- Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Compliance(Baseline and Weeks 3, 6, 9, 12, 24, 52)
- Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Detrusor Pressure at End of Bladder-Filling(Baseline and Weeks 3, 6, 9, 12, 24, 52)
- Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Detrusor Pressure 5 Minutes After End of Bladder-Filling(Baseline and Weeks 3, 6, 9, 12, 24, 52)
- Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Catheterized Volume 5 Minutes After End of Bladder-Filling(Baseline and Weeks 3, 6, 9, 12, 24, 52)
- Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume Until First Detrusor Contraction (> 15 cmH2O)(Baseline and Weeks 3, 6, 9, 12, 24, 52)
- Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Bladder Volume at 20 cmH20 Detrusor Pressure(Baseline and Weeks 3, 6, 9, 12, 24, 52)
- Change From Baseline to Weeks 3, 6, 9, 12, 24 and 52 in Number of Overactive Detrusor Contractions (> 15 cmH2O) Until Leakage or End of Bladder-Filling(Baseline and Weeks 3, 6, 9, 12, 24, 52)
- Percentage of Days With Catheterizations for Each Hour of 24 Hour Day at Baseline(3 days prior to Baseline visit)
- Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 24(3 days prior to Week 24 visit)
- Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 36(3 days prior to Week 36 visit)
- Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 52(3 days prior to Week 52 visit)
- Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 6(3 days prior to Week 6 visit)
- Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 9(3 days prior to Week 9 visit)
- Change From Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Average Catheterized Volume Per Catheterization(Baseline and Weeks 3, 6, 9, 12, 24, 36, 52)
- Change From Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Maximum Catheterized Volume (MCV)(Baseline and Weeks 3, 6, 9, 12, 24, 36, 52)
- Change From Baseline to Weeks 3, 6, 9, 12, 24, 36 and 52 in Mean Number of Periods Between the Clean Intermittent Catheterizations (CICs) With Incontinence Per 24 Hours(Baseline and Weeks 3, 6, 9, 12, 24, 36, 52)
- Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 3(3 days prior to Week 3 visit)
- Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 6(3 days prior to Week 6 visit)
- Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 9(3 days prior to Week 9 visit)
- Percentage of Days With Catheterizations for Each Hour of 24 Hour Day During Week 12(3 days prior to Week 12 visit)
- Percentage of Days With Incontinence for Each Hour of 24 Hour Day at Baseline(3 days prior to Baseline visit)
- Percentage of Days With of Incontinence for Each Hour of 24 Hour Day During Week 3(3 days prior to Week 3 visit)
- Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Change in Health Score(Baseline and Weeks 24, 52)
- Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Parent-Emotional Impact Score(Baseline and Weeks 24, 52)
- Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Parent-Time Impact Score(Baseline and Weeks 24, 52)
- Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 24(3 days prior to Week 24 visit)
- Change From Baseline to Week 24 and 52 in Infant and Toddler Quality of Life Short Form-47 Questionnaire (ITQoL SF-47) - Overall Health Score(Baseline and Weeks 24, 52)
- Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 36(3 days prior to Week 36 visit)
- Percentage of Days With Incontinence for Each Hour of 24 Hour Day During Week 52(3 days prior to Week 52 visit)
- Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Physical Abilities Score(Baseline and Weeks 24, 52)
- Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Growth and Development Score(Baseline and Weeks 24, 52)
- Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Pain Score(Baseline and Weeks 24, 52)
- Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Temperament and Moods Score(Baseline and Weeks 24, 52)
- Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Behaviour Score(Baseline and Weeks 24, 52)
- Change From Baseline to Week 24 and 52 in ITQoL SF-47 - General Health Score(Baseline and Weeks 24, 52)
- Change From Baseline to Week 24 and 52 in ITQoL SF-47 - Family Cohesion Impact Score(Baseline and Weeks 24, 52)