Alfuzosin Treatment in Children and Adolescents With Neurogenic Urinary Bladder Dysfunction

Official Title: “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”

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: - To investigate the safety and tolerability of two doses of Alfuzosin in comparison to Placebo in children and adolescents, - To evaluate the effects of the two doses of Alfuzosin in comparison to Placebo on: - Detrusor compliance, - Urinary tract infection, - To investigate the pharmacokinetics of Alfuzosin (population kinetics), - 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.

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.

All patients had a one-week follow-up period after last dose intake.

Intervention(s) in this Clinical Trial

• Drug: Alfuzosin
  • Form: solution or tablet according to age Route: oral Dose: daily dose adjusted to body weight
• Drug: Placebo
  • Form: matching solution or matching tablet according to age Route: oral Dose: daily dose adjusted to body weight

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: Placebo
  • Matching placebo 0.1 mg/kg/day or 0.2 mg/kg/day
• Experimental: Alfuzosin 0.1 mg/kg/day
• Experimental: Alfuzosin 0.2 mg/kg/day

Primary Measures

• Number of Patients With Detrusor Leak Point Pressure (LPP) < 40 cm H2O
  • Time Frame: 12 weeks (double blind treatment period)
    Safety Issue?: No

Secondary Measures

• Detrusor Leak Point Pressure (LPP)
  • Time Frame: baseline and 12 weeks (double blind treatment period)
    Safety Issue?: No
• Absolute Change in Detrusor LPP
  • Time Frame: 12 weeks ((double blind treatment period)
    Safety Issue?: No
• Relative Change in Detrusor LPP
  • Time Frame: 12 weeks (double blind treatment period)
    Safety Issue?: No
• Detrusor Compliance
  • Time Frame: baseline and 12 weeks (double blind treatment period)
    Safety Issue?: No
• Relative Change in Detrusor Compliance
  • Time Frame: 12 weeks (double blind treatment period)
    Safety Issue?: No
• Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes
  • Time Frame: 12 weeks (double blind treatment period)
    Safety Issue?: No
• Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes
  • Time Frame: 52 weeks (double blind treatment period + open label extension treatment period)
    Safety Issue?: No

Inclusion Criteria:

• Patient with elevated detrusor Leak Point Pressure (LPP) of neuropathic etiology and Detrusor LPP ≥ 40 cm H2O and < 100 cm H2O.

Exclusion Criteria:

• 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 2 Years

Maximum Age for this Clinical Trial: 16 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Sanofi-Aventis Industry

Overall Clinical Trial Officials and Contacts

ICD CSD Study Director Sanofi-Aventis  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00549939

Study ID Number: EFC5722

ClinicalTrials.gov Identifier: NCT00549939

Health Authority: United States: Food and Drug Administration