Alfuzosin Treatment in Children and Adolescents With Neurogenic Urinary Bladder Dysfunction

Neurogenic Urinary Bladder Clinical Trial

— ALFACHIN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00549939
• Other study ID #: EFC5722
• Secondary ID: 2004-002397-38
• Status: Completed
• Phase: Phase 3
• First received: October 25, 2007
• Last updated: October 21, 2014
• Start date: October 2007
• Est. completion date: December 2009

Study information

• Verified date: October 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationPoland: Ministry of HealthSerbia: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 172
• Est. completion date: December 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 16 Years

Eligibility

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,

• a-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 a-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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neurogenic Urinary Bladder
• Urinary Bladder, Neurogenic

Intervention

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

Locations

Country	Name	City	State
Bulgaria	Sanofi-Aventis Administrative Office	Sofia
Canada	Sanofi-Aventis Administrative Office	Laval
Estonia	Sanofi-Aventis Administrative Office	Tallinn
France	Sanofi-Aventis Administrative Office	Paris
Germany	Sanofi-Aventis Administrative Office	Berlin
India	Sanofi-Aventis Administrative Office	Mumbai
Malaysia	Sanofi-Aventis Administrative Office	Kuala Lumpur
Philippines	Sanofi-Aventis Administrative Office	Makati City
Poland	Sanofi-Aventis Administrative Office	Warszawa
Portugal	Sanofi-Aventis Administrative Office	Porto Salvo
Russian Federation	Sanofi-Aventis Aministrative Office	Moscow
Serbia	Sanofi-Aventis Administrative Office	Belgrade
Singapore	Sanofi-Aventis Administrative Office	Singapore
Slovakia	Sanofi-Aventis Administrative Office	Bratislava
Spain	Sanofi-Aventis Administrative Office	Barcelona
Taiwan	Sanofi-Aventis Administrative Office	Taipei
Turkey	Sanofi-Aventis Administrative Office	Istanbul
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Estonia,  France,  Germany,  India,  Malaysia,  Philippines,  Poland,  Portugal,  Russian Federation,  Serbia,  Singapore,  Slovakia,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Detrusor Leak Point Pressure (LPP) < 40 cm H2O	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).	12 weeks (double blind treatment period)	No
Secondary	Detrusor Leak Point Pressure (LPP)	Detrusor Leak Point Pressure (LPP) was assessed at baseline and 12 weeks as described for the primary outcome measure.	baseline and 12 weeks (double blind treatment period)	No
Secondary	Absolute Change in Detrusor LPP	Absolute change = Detrusor LPP at 12 weeks - Detrusor LPP at baseline	12 weeks ((double blind treatment period)	No
Secondary	Relative Change in Detrusor LPP	Relative change = 100 * (Detrusor LPP at 12 weeks - Detrusor LPP at baseline) / Detrusor LPP at baseline	12 weeks (double blind treatment period)	No
Secondary	Detrusor Compliance	Detrusor compliance is defined as the relationship between change in detrusor volume and change in detrusor pressure.; It was calculated by dividing the volume change (?V) by the change in detrusor pressure (?pdet) during that change in detrusor volume at leak point (C= ?V/?pdet).	baseline and 12 weeks (double blind treatment period)	No
Secondary	Relative Change in Detrusor Compliance	Relative change = 100 * (Detrusor compliance at 12 weeks - Detrusor compliance at baseline) / Detrusor compliance at baseline	12 weeks (double blind treatment period)	No
Secondary	Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes	When a patient presented with symptoms such as pain, fever or hematuria (discretion of the Investigator), an urinalysis was performed including a dipstick and a quantitative urine culture.; A symptomatic UTI was defined as the presence of symptoms and a positive culture with > 100 000 Colony Forming Units (CFUs) with a single organism.	12 weeks (double blind treatment period)	No
Secondary	Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes	Symptomatic UTI episodes were assessed similar to the previous outcome measure but for a longer follow-up period.	52 weeks (double blind treatment period + open label extension treatment period)	No