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

• ClinicalTrials.gov Identifier: NCT00549939
• Recruitment Status: Completed
• First Posted: October 26, 2007
• Results First Posted: February 8, 2011
• Last Update Posted: October 29, 2014
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Neurogenic Urinary Bladder	Drug: Alfuzosin; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 172 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: October 2007
• Actual Primary Completion Date: March 2009
• Actual Study Completion Date: December 2009

Arms and Interventions

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 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

Outcome Measures

Primary Outcome Measures :

1. Number of Patients With Detrusor Leak Point Pressure (LPP) < 40 cm H2O [ Time Frame: 12 weeks (double blind treatment period) ]

   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 :

1. Detrusor Leak Point Pressure (LPP) [ Time Frame: baseline and 12 weeks (double blind treatment period) ]
   Detrusor Leak Point Pressure (LPP) was assessed at baseline and 12 weeks as described for the primary outcome measure.
2. Absolute Change in Detrusor LPP [ Time Frame: 12 weeks ((double blind treatment period) ]
   Absolute change = Detrusor LPP at 12 weeks - Detrusor LPP at baseline
3. Relative Change in Detrusor LPP [ Time Frame: 12 weeks (double blind treatment period) ]
   Relative change = 100 * (Detrusor LPP at 12 weeks - Detrusor LPP at baseline) / Detrusor LPP at baseline
4. Detrusor Compliance [ Time Frame: baseline and 12 weeks (double blind treatment period) ]

   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).

5. Relative Change in Detrusor Compliance [ Time Frame: 12 weeks (double blind treatment period) ]
   Relative change = 100 * (Detrusor compliance at 12 weeks - Detrusor compliance at baseline) / Detrusor compliance at baseline
6. Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes [ Time Frame: 12 weeks (double blind treatment period) ]

   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.

7. Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes [ Time Frame: 52 weeks (double blind treatment period + open label extension treatment period) ]
   Symptomatic UTI episodes were assessed similar to the previous outcome measure but for a longer follow-up period.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 16 Years (Child)
• Sexes Eligible for Study: All
• 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

Locations

United States, New Jersey

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States, 08807

Bulgaria

Sanofi-Aventis Administrative Office

Sofia, Bulgaria

Canada

Sanofi-Aventis Administrative Office

Laval, Canada

Estonia

Sanofi-Aventis Administrative Office

Tallinn, Estonia

France

Sanofi-Aventis Administrative Office

Paris, France

Germany

Sanofi-Aventis Administrative Office

Berlin, Germany

India

Sanofi-Aventis Administrative Office

Mumbai, India

Malaysia

Sanofi-Aventis Administrative Office

Kuala Lumpur, Malaysia

Philippines

Sanofi-Aventis Administrative Office

Makati City, Philippines

Poland

Sanofi-Aventis Administrative Office

Warszawa, Poland

Portugal

Sanofi-Aventis Administrative Office

Porto Salvo, Portugal

Russian Federation

Sanofi-Aventis Aministrative Office

Moscow, Russian Federation

Serbia

Sanofi-Aventis Administrative Office

Belgrade, Serbia

Singapore

Sanofi-Aventis Administrative Office

Singapore, Singapore

Slovakia

Sanofi-Aventis Administrative Office

Bratislava, Slovakia

Spain

Sanofi-Aventis Administrative Office

Barcelona, Spain

Taiwan

Sanofi-Aventis Administrative Office

Taipei, Taiwan

Turkey

Sanofi-Aventis Administrative Office

Istanbul, Turkey

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: ICD CSD; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT00549939
• Other Study ID Numbers: EFC5722; 2004-002397-38 ( EudraCT Number )
• First Posted: October 26, 2007
• Results First Posted: February 8, 2011
• Last Update Posted: October 29, 2014
• Last Verified: October 2014

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; Alfuzosin; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Urological Agents