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

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00549939
First received: October 25, 2007
Last updated: February 15, 2011
Last verified: February 2011
  Purpose

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.

Condition Intervention Phase
Neurogenic Urinary Bladder
Drug: Alfuzosin
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Number of Patients With Detrusor Leak Point Pressure (LPP) < 40 cm H2O [ Time Frame: 12 weeks (double blind treatment period) ] [ Designated as safety issue: No ]

    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).



Secondary Outcome Measures:
  • Detrusor Leak Point Pressure (LPP) [ Time Frame: baseline and 12 weeks (double blind treatment period) ] [ Designated as safety issue: No ]
    Detrusor Leak Point Pressure (LPP) was assessed at baseline and 12 weeks as described for the primary outcome measure.

  • Absolute Change in Detrusor LPP [ Time Frame: 12 weeks ((double blind treatment period) ] [ Designated as safety issue: No ]
    Absolute change = Detrusor LPP at 12 weeks - Detrusor LPP at baseline

  • Relative Change in Detrusor LPP [ Time Frame: 12 weeks (double blind treatment period) ] [ Designated as safety issue: No ]
    Relative change = 100 * (Detrusor LPP at 12 weeks - Detrusor LPP at baseline) / Detrusor LPP at baseline

  • Detrusor Compliance [ Time Frame: baseline and 12 weeks (double blind treatment period) ] [ Designated as safety issue: No ]

    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).


  • Relative Change in Detrusor Compliance [ Time Frame: 12 weeks (double blind treatment period) ] [ Designated as safety issue: No ]
    Relative change = 100 * (Detrusor compliance at 12 weeks - Detrusor compliance at baseline) / Detrusor compliance at baseline

  • Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes [ Time Frame: 12 weeks (double blind treatment period) ] [ Designated as safety issue: No ]

    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.


  • Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes [ Time Frame: 52 weeks (double blind treatment period + open label extension treatment period) ] [ Designated as safety issue: No ]
    Symptomatic UTI episodes were assessed similar to the previous outcome measure but for a longer follow-up period.


Enrollment: 172
Study Start Date: October 2007
Study Completion Date: December 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: SL770499

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

Ages Eligible for Study:   2 Years to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00549939

  Show 18 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: ICD CSD Sanofi
  More Information

No publications provided

Responsible Party: International Clinical Development Study Director, sanofi-aventis
ClinicalTrials.gov Identifier: NCT00549939     History of Changes
Other Study ID Numbers: EFC5722, 2004-002397-38
Study First Received: October 25, 2007
Results First Received: January 13, 2011
Last Updated: February 15, 2011
Health Authority: United States: Food and Drug Administration
Poland: Ministry of Health
Serbia: Ethics Committee

Keywords provided by Sanofi:
child
bladder
neuropathic
alpha blockers

Additional relevant MeSH terms:
Urinary Bladder, Neurogenic
Neurologic Manifestations
Nervous System Diseases
Urinary Bladder Diseases
Urologic Diseases
Signs and Symptoms
Alfuzosin
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Urological Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014