Alfuzosin Treatment in Children and Adolescents With Neurogenic Urinary Bladder Dysfunction (ALFACHIN)

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.

Study Overview

• Status: Completed
• Conditions: Neurogenic Urinary Bladder
• Intervention / Treatment: Drug: Placebo; Drug: Alfuzosin

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.

• Study Type: Interventional
• Enrollment (Actual): 172
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • Sanofi-Aventis Administrative Office
• Canada
  • Laval, Canada
    • Sanofi-Aventis Administrative Office
• Estonia
  • Tallinn, Estonia
    • Sanofi-Aventis Administrative Office
• France
  • Paris, France
    • Sanofi-Aventis Administrative Office
• Germany
  • Berlin, Germany
    • Sanofi-Aventis Administrative Office
• India
  • Mumbai, India
    • Sanofi-Aventis Administrative Office
• Malaysia
  • Kuala Lumpur, Malaysia
    • Sanofi-Aventis Administrative Office
• Philippines
  • Makati City, Philippines
    • Sanofi-Aventis Administrative Office
• Poland
  • Warszawa, Poland
    • Sanofi-Aventis Administrative Office
• Portugal
  • Porto Salvo, Portugal
    • Sanofi-Aventis Administrative Office
• Russian Federation
  • Moscow, Russian Federation
    • Sanofi-Aventis Aministrative Office
• Serbia
  • Belgrade, Serbia
    • Sanofi-Aventis Administrative Office
• Singapore
  • Singapore, Singapore
    • Sanofi-Aventis Administrative Office
• Slovakia
  • Bratislava, Slovakia
    • Sanofi-Aventis Administrative Office
• Spain
  • Barcelona, Spain
    • Sanofi-Aventis Administrative Office
• Taiwan
  • Taipei, Taiwan
    • Sanofi-Aventis Administrative Office
• Turkey
  • Istanbul, Turkey
    • Sanofi-Aventis Administrative Office
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo 0.1 mg/kg/day or 0.2 mg/kg/day	Drug: Placebo; Form: matching solution or matching tablet according to age Route: oral Dose: daily dose adjusted to body weight
Experimental: Alfuzosin 0.1 mg/kg/day	Drug: Alfuzosin; Form: solution or tablet according to age Route: oral Dose: daily dose adjusted to body weight; Other Names: SL770499
Experimental: Alfuzosin 0.2 mg/kg/day	Drug: Alfuzosin; Form: solution or tablet according to age Route: oral Dose: daily dose adjusted to body weight; Other Names: SL770499

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Absolute Change in Detrusor LPP	Absolute change = Detrusor LPP at 12 weeks - Detrusor LPP at baseline	12 weeks ((double blind treatment period)
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)
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 (ΔV) by the change in detrusor pressure (Δpdet) during that change in detrusor volume at leak point (C= ΔV/Δpdet).	baseline and 12 weeks (double blind treatment period)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: October 25, 2007
• First Submitted That Met QC Criteria: October 25, 2007
• First Posted (Estimate): October 26, 2007

Study Record Updates

• Last Update Posted (Estimate): October 29, 2014
• Last Update Submitted That Met QC Criteria: October 21, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: child; bladder; neuropathic; alpha blockers
• Additional Relevant MeSH Terms: Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Neurologic Manifestations; Urinary Bladder, Neurogenic; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Alfuzosin
• Other Study ID Numbers: EFC5722; 2004-002397-38 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No