Clinical trial NCT00549939: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neurogenic Urinary Bladder
Keywords: child
bladder
neuropathic
alpha blockers
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2007-10-26
Enrollment: 172
Sex: ALL
Minimum age (years): 2
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Patients With Detrusor Leak Point Pressure (LPP) < 40 cm H2O
timeFrame: 12 weeks (double blind treatment period)
Secondary outcomes:
measure: Detrusor Leak Point Pressure (LPP)
timeFrame: baseline and 12 weeks (double blind treatment period)
measure: Absolute Change in Detrusor LPP
timeFrame: 12 weeks ((double blind treatment period)
measure: Relative Change in Detrusor LPP
timeFrame: 12 weeks (double blind treatment period)
measure: Detrusor Compliance
timeFrame: baseline and 12 weeks (double blind treatment period)
measure: Relative Change in Detrusor Compliance
timeFrame: 12 weeks (double blind treatment period)
measure: Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes
timeFrame: 12 weeks (double blind treatment period)
measure: Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes
timeFrame: 52 weeks (double blind treatment period + open label extension treatment period)
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Sofia
country: Bulgaria
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Tallinn
country: Estonia
facility: Sanofi-Aventis Administrative Office
city: Paris
country: France
facility: Sanofi-Aventis Administrative Office
city: Berlin
country: Germany
facility: Sanofi-Aventis Administrative Office
city: Mumbai
country: India
facility: Sanofi-Aventis Administrative Office
city: Kuala Lumpur
country: Malaysia
facility: Sanofi-Aventis Administrative Office
city: Makati City
country: Philippines
facility: Sanofi-Aventis Administrative Office
city: Warszawa
country: Poland
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis Aministrative Office
city: Belgrade
country: Serbia
facility: Sanofi-Aventis Administrative Office
city: Singapore
country: Singapore
facility: Sanofi-Aventis Administrative Office
city: Bratislava
country: Slovakia
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Taipei
country: Taiwan
facility: Sanofi-Aventis Administrative Office
city: Istanbul
country: Turkey
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: ICD CSD
role: STUDY_DIRECTOR
References: