12-week, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Efficacy, Pharmacodynamic and Safety of 2 Doses of Alfuzosin (0.1 mg/kg/Day, 0.2 mg/kg/Day) in the Treatment of Children and Adolescents 2-16 Years With Elevated Detrusor Leak Point Pressure of Neuropathic Etiology Followed by a 40-week Open-label Extension
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 172
- 试验地点
- 2
- 主要终点
- Number of Patients With Detrusor Leak Point Pressure (LPP) < 40 cm H2O
研究概览
简要总结
The primary objective of the study was to evaluate the efficacy of Alfuzosin in comparison to Placebo on the detrusor Leak Point Pressure (LPP) in children and adolescents 2-16 years of age with elevated detrusor LPP of neuropathic etiology and detrusor LPP ≥ 40 cm H2O.
Secondary objectives were:
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To investigate the safety and tolerability of two doses of Alfuzosin in comparison to Placebo in children and adolescents,
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To evaluate the effects of the two doses of Alfuzosin in comparison to Placebo on:
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Detrusor compliance,
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Urinary tract infection,
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To investigate the pharmacokinetics of Alfuzosin (population kinetics),
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To evaluate the 12-month long-term safety of Alfuzosin 0.1 mg/kg/day and 0.2 mg/kg/day.
The study consisted of 2 periods:
- a 12-week double blind treatment period where patients were to receive either Alfuzosin 0.1 mg/kg/day or Alfuzosin 0.2 mg/kg/day or placebo then,
- a 40-week open label extension treatment period where patients were to receive either Alfuzosin 0.1 mg/kg/day or Alfuzosin 0.2 mg/kg/day.
详细描述
Patients who met the study entry criteria were randomized (2:1:2:1) to one of the 4 dosage groups (Alfuzosin 0.1 mg/kg/day, matching placebo 0.1 mg/kg/day, Alfuzosin 0.2 mg/mg/kg, matching placebo 0.2 mg/kg/day).
Patients received their treatment using either solution or tablet formulation depending on age as follows:
- Solution to children 2-7 years of age or, children and adolescents 8-16 years of age if they were unable to swallow tablets or they preferred to take the solution or if they had a body weight < 30kg. The daily dose was devided in 3 doses given at at breakfast, lunch and dinner.
- Tablet to children and adolescents 8-16 years of age who were able to swallow tablets and had a body weight ≥ 30kg. The daily dose was devided in 2 doses given at at breakfast and dinner.
Patients who have completed the 12-week double-blind phase were offered to continue in the 40-week open-label extension study.
- Patients receiving Alfuzosin continued with their dosing regimen.
- Patients receiving Placebo were switched to Alfuzosin with a dose corresponding to their randomization dose group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with elevated detrusor Leak Point Pressure (LPP) of neuropathic etiology and Detrusor LPP ≥ 40 cm H2O and < 100 cm H2O.
排除标准
- •Urological surgery in the last 4 months prior to the study,
- •Patients who have urethral dilatation in the last 3 months prior to the baseline urodynamic assessment,
- •α-blocker therapy in the last 4 weeks prior to the baseline urodynamic assessment,
- •Detrusor injections of botulinum toxin in the last 6 months,
- •Urological diseases/conditions other than functional bladder obstruction of neuropathic etiology that can lead to upper urinary tract dilatation (e.g., bladder anomalies, ureterocele),
- •History of intolerance to α-blocker therapy,
- •Orthostatic hypotension,
- •History of risk factors for Torsade de pointes (e.g., family history of Long QT Syndrome).
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Placebo
Matching placebo 0.1 mg/kg/day or 0.2 mg/kg/day
干预措施: Placebo (Drug)
Alfuzosin 0.1 mg/kg/day
干预措施: Alfuzosin (Drug)
Alfuzosin 0.2 mg/kg/day
干预措施: Alfuzosin (Drug)
结局指标
主要结局
Number of Patients With Detrusor Leak Point Pressure (LPP) < 40 cm H2O
时间窗: 12 weeks (double blind treatment period)
Detrusor Leak Point Pressure (LPP) was measured by cystometry. For each measure, 2 or 3 cystometries were carried out depending on the difference between the 2 first LPP values (if the difference ≥ 20 cm H2O, a 3rd cystometry was done). The lowest value was retained. Investigators reading was then consolidated by the review of all cystometry data by 2 external "Expert Reviewers", who were blinded for the study treatment. The analysis was performed on consolidated investigators data (i.e. endorsed by the Investigator taking into account reviewers opinion).
次要结局
- Absolute Change in Detrusor LPP(12 weeks ((double blind treatment period))
- Detrusor Leak Point Pressure (LPP)(baseline and 12 weeks (double blind treatment period))
- Relative Change in Detrusor Compliance(12 weeks (double blind treatment period))
- Relative Change in Detrusor LPP(12 weeks (double blind treatment period))
- Detrusor Compliance(baseline and 12 weeks (double blind treatment period))
- Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes(52 weeks (double blind treatment period + open label extension treatment period))