A 14-day, Open-label, Multicenter, Dose-escalating, Sequential Cohort Study to Evaluate Pharmacodynamics (Urodynamics) and Pharmacokinetics, Clinical Efficacy, Tolerability and Safety Following Multiple Doses (mg/kg/Day) of a Darifenacin Liquid Oral Suspension Given BID in Children, Ages 2 - 15 Years, With Neurogenic Detrusor Overactivity
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 35
- 试验地点
- 12
- 主要终点
- Change From Baseline in Mean Maximum Bladder Capacity (MBC)
研究概览
简要总结
This study will evaluate the pharmacodynamics and pharmacokinetics of darifenacin liquid oral suspension in children, ages 2-15 years, with neurogenic detrusor overactivity. The results will support a benefit-risk based dosage recommendation for phase IIIa clinical trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants ages 2-15 years
- •Documented detrusor overactivity associated with a known neurological condition such as meningomyelocele or spinal cord injury, and confirmed by urodynamics at baseline
- •Using clean intermittent catheterization (CIC) on a regular basis
- •Participating in a bowel program on a regular basis
- •Able to swallow the study medication in accordance to the protocol
- •Participants and/or parent/guardian able to complete the bladder diary and follow the study procedures
排除标准
- •Treatment with drugs known to significantly affect the urinary bladder and urinary bladder outlet function
- •Fecal impaction. Participants may be included, once this condition has resolved
- •Clinically significant anatomical abnormalities or acquired disorders of the urinary tract
- •Previous reconstructive surgery (augmentation etc.) of the bladder or bladder outlet
- •Symptomatic urinary tract infection unresolved at time of urodynamic study and/or completion of bladder diary.
- •Diabetes insipidus
- •Electro stimulation therapy or bladder training within 2 weeks prior to Visit 1 and at any time during the study
- •Concomitant diseases, in which the use of darifenacin is contraindicated
- •History of hypersensitivity to darifenacin or to drugs with similar chemical structures
- •Participants with any physical and cognitive impairment or any other condition which in the opinion of the investigator makes the participants unsuitable for inclusion
- •Female adolescent of child-bearing potential, unless using an acceptable method of contraception
- •Pregnant or nursing (lactating) female adolescents Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Cohort 1 (Darifenacin 0.030 mg/kg/day)
Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 milligrams/kilogram/day (mg/kg/day) dispensed per twice a day (BID) dosing, for 14 days.
干预措施: Darifenacin (Drug)
Cohort 2 (Darifenacin 0.0625 mg/kg/day)
Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.0625 mg/kg/day dispensed per BID dosing, for 14 days.
干预措施: Darifenacin (Drug)
Cohort 3 (Darifenacin 0.125 mg/kg/day)
Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.125 mg/kg/day dispensed per BID dosing, for 14 days.
干预措施: Darifenacin (Drug)
结局指标
主要结局
Change From Baseline in Mean Maximum Bladder Capacity (MBC)
时间窗: Baseline (Day 0) to Day 14
MBC was defined as the volume of urine at which significant urinary leakage (i.e. leakage that prevents further volume increase) or significant discomfort/pain occurs, or a detrusor pressure at 40 centimeter (cm) H2O was reached.
次要结局
- Change From Baseline in Mean Catheterization Volume at First Awakening(Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14)
- Change From Baseline in Mean Volume at First Contraction(Baseline (Day 0) to Day 14)
- Change From Baseline in Mean Volume at First Detectable Leakage(Baseline (Day 0) to Day 14)
- Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure(Baseline (Day 0) to Day 14)
- Change From Baseline in Detrusor Pressure at First Contraction(Baseline (Day 0) to Day 14)
- Change From Baseline in Mean Catheterization Volume(Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14)
- Change From Baseline in Total Pad Weight In-between Catheterizations(Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14)