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CompletedNCT00549939ALFACHINUpdated Oct 29, 2014Results posted

Alfuzosin Treatment in Children and Adolescents With Neurogenic Urinary Bladder Dysfunction

A Phase 3 interventional study of Alfuzosin and Placebo in Neurogenic Urinary Bladder, sponsored by Sanofi. Completed at 18 sites in 18 countries. Open to participants aged 2 Years to 16 Years. Per ClinicalTrials.gov, last updated 2014-10-29.

Sponsored by Sanofi · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
172
Allocation
Randomized
Ages
2 Years to 16 Years
Sex
All
01

Study 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.
Read the 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.

02

Conditions studied

  • Neurogenic Urinary Bladder

Keywords

  • child
  • bladder
  • neuropathic
  • alpha blockers
03

In context

Urinary Bladder, Neurogenic

185 studies on the registry are indexed under Urinary Bladder, Neurogenic; 40 are open to participants now.

This study's enrollment of 172 is above the median of 36 across 124 interventional studies indexed under Urinary Bladder, Neurogenic.

Browse Urinary Bladder, Neurogenic studies →

Lead sponsor

Sanofi is the lead sponsor of 1,508 studies on the registry; 90 are open to participants now.

Of its 198 completed or terminated interventional studies of FDA-regulated products, 118 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
2 Years to 16 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
172 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    Matching placebo 0.1 mg/kg/day or 0.2 mg/kg/day

    Drug: Placebo

  • Experimental
    Alfuzosin 0.1 mg/kg/day

    Drug: Alfuzosin

  • Experimental
    Alfuzosin 0.2 mg/kg/day

    Drug: Alfuzosin

Interventions

  • DrugAlfuzosin

    Form: solution or tablet according to age Route: oral Dose: daily dose adjusted to body weight

    Also known as: SL770499

  • DrugPlacebo

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

06

What researchers measure

Primary outcomes

  1. 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).

    Time frame: 12 weeks (double blind treatment period)

Secondary outcomes

  1. Detrusor Leak Point Pressure (LPP)

    Detrusor Leak Point Pressure (LPP) was assessed at baseline and 12 weeks as described for the primary outcome measure.

    Time frame: baseline and 12 weeks (double blind treatment period)

  2. Absolute Change in Detrusor LPP

    Absolute change = Detrusor LPP at 12 weeks - Detrusor LPP at baseline

    Time frame: 12 weeks ((double blind treatment period)

  3. Relative Change in Detrusor LPP

    Relative change = 100 \* (Detrusor LPP at 12 weeks - Detrusor LPP at baseline) / Detrusor LPP at baseline

    Time frame: 12 weeks (double blind treatment period)

  4. 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).

    Time frame: baseline and 12 weeks (double blind treatment period)

  5. Relative Change in Detrusor Compliance

    Relative change = 100 \* (Detrusor compliance at 12 weeks - Detrusor compliance at baseline) / Detrusor compliance at baseline

    Time frame: 12 weeks (double blind treatment period)

  6. 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.

    Time frame: 12 weeks (double blind treatment period)

  7. 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.

    Time frame: 52 weeks (double blind treatment period + open label extension treatment period)

07

Results

Posted Feb 8, 2011

Participant flow

The study was conducted at 55 sites in 18 countries. A total of 261 patients were screened between September 2007 and November 2008.

12-week Double Blind Treatment Period
Participant flow — 12-week Double Blind Treatment Period
MilestonePlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/Day
Started575758
Completed565556
Not completed122
Withdrew: Adverse event112
Withdrew: Too many blood draws010
40-week Open Label Treatment Period
Participant flow — 40-week Open Label Treatment Period
MilestonePlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/Day
Started08083
Completed07578
Not completed055
Withdrew: Adverse event021
Withdrew: Lack of efficacy010
Withdrew: Protocol violation010
Withdrew: Other014

Outcome measures

PrimaryNumber 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).

Time frame:
12 weeks (double blind treatment period)
Reported as:
Number · participants
Number of Patients With Detrusor Leak Point Pressure (LPP) < 40 cm H2O
participantsPlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/Day
< 40 cmH2O ("Success")232328
≥ 40 cmH2O or missing ("Failure")343430
Statistical analysis
  • Placebo vs Alfuzosin 0.1 mg/kg/Day · Fisher Exact · p = 1.00 (P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.)
  • Placebo vs Alfuzosin 0.2 mg/kg/Day · Fisher Exact · p = 0.91 (P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.)
SecondaryDetrusor Leak Point Pressure (LPP)

Detrusor Leak Point Pressure (LPP) was assessed at baseline and 12 weeks as described for the primary outcome measure.

Time frame:
baseline and 12 weeks (double blind treatment period)
Reported as:
Mean · cmH2O
Detrusor Leak Point Pressure (LPP)
cmH2OPlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/Day
Baseline54.2 ± 12.653.3 ± 13.450.9 ± 10.0
12 Weeks48.2 ± 23.441.6 ± 18.239.4 ± 19.5
SecondaryAbsolute Change in Detrusor LPP

Absolute change = Detrusor LPP at 12 weeks - Detrusor LPP at baseline

Time frame:
12 weeks ((double blind treatment period)
Reported as:
Least squares mean · cmH2O
Absolute Change in Detrusor LPP
cmH2OPlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/Day
Absolute Change in Detrusor LPP-5.4 ± 2.8-11.7 ± 2.8-12.5 ± 2.8
Statistical analysis
  • Placebo vs Alfuzosin 0.1 mg/kg/Day · ANCOVA · p = 0.1040 (P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.) · Ls mean difference versus placebo: -6.2 · 95% CI -13.72 to 1.29
  • Placebo vs Alfuzosin 0.2 mg/kg/Day · ANCOVA · p = 0.1040 (P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.) · Ls mean difference versus placebo: -7.1 · 95% CI -14.51 to 0.39
SecondaryRelative Change in Detrusor LPP

Relative change = 100 \* (Detrusor LPP at 12 weeks - Detrusor LPP at baseline) / Detrusor LPP at baseline

Time frame:
12 weeks (double blind treatment period)
Reported as:
Least squares mean · percentage of cmH2O
Relative Change in Detrusor LPP
percentage of cmH2OPlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/Day
Relative Change in Detrusor LPP-9.2 ± 5.53-20.6 ± 5.56-23.5 ± 5.51
Statistical analysis
  • Placebo vs Alfuzosin 0.1 mg/kg/Day · ANCOVA · p = 0.1338 (P-values was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.) · Ls mean difference versus placebo: -11.4 · 95% CI -26.27 to 3.53
  • Placebo vs Alfuzosin 0.2 mg/kg/Day · ANCOVA · p = 0.1152 (P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.) · Ls mean difference versus placebo: -14.3 · 95% CI -29.10 to 0.47
SecondaryDetrusor 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).

Time frame:
baseline and 12 weeks (double blind treatment period)
Reported as:
Mean · mL/cmH20
Detrusor Compliance
mL/cmH20PlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/Day
Baseline3.4 ± 2.83.4 ± 2.83.3 ± 2.5
12 weeks4.8 ± 5.05.3 ± 4.95.8 ± 5.9
SecondaryRelative Change in Detrusor Compliance

Relative change = 100 \* (Detrusor compliance at 12 weeks - Detrusor compliance at baseline) / Detrusor compliance at baseline

Time frame:
12 weeks (double blind treatment period)
Reported as:
Least squares mean · percentage of mL/cmH2O
Relative Change in Detrusor Compliance
percentage of mL/cmH2OPlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/Day
Relative Change in Detrusor Compliance113.6 ± 35.26126.6 ± 35.7698.6 ± 35.24
Statistical analysis
  • Placebo vs Alfuzosin 0.1 mg/kg/Day · ANCOVA · p = 0.7889 (P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.)
  • Placebo vs Alfuzosin 0.2 mg/kg/Day · ANCOVA · p = 0.7889 (P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05.)
SecondaryNumber 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.

Time frame:
12 weeks (double blind treatment period)
Reported as:
Number · participants
Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes
participantsPlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/Day
No symptomatic UTI505351
One symptomatic UTI536
Two symptomatic UTI211
SecondaryNumber 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.

Time frame:
52 weeks (double blind treatment period + open label extension treatment period)
Reported as:
Number · participants
Number of Participants With Symptomatic Urinary Tract Infection (UTI) Episodes
participantsAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/Day
No symptomatic UTI6670
One symptomatic UTI1213
Two symptomatic UTI30
Three symptomatic UTI11
Four symptomatic UTI12

Adverse events

Collected over All Adverse Events (AE) regardless of seriousness or relationship to drug, spanning from signature of the Informed Consent Form up to the last visit were collected.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Alfuzosin 0.1 mg/kg/Day—10/83 (12%)37/83 (44.6%)
Alfuzosin 0.2 mg/kg/Day—7/86 (8.1%)43/86 (50%)
Most frequent serious events
Showing 10 of 16
Most frequent serious events
EventAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/Day
EPILEPSYNervous system disorders2/830/86
DECUBITUS ULCERSkin and subcutaneous tissue disorders0/832/86
PNEUMONIAInfections and infestations1/831/86
LOBAR PNEUMONIAInfections and infestations1/830/86
MALNUTRITIONMetabolism and nutrition disorders1/830/86
TETHERED CORD SYNDROMENervous system disorders1/831/86
RESPIRATORY FAILURERespiratory, thoracic and mediastinal disorders1/830/86
TONSILLAR HYPERTROPHYRespiratory, thoracic and mediastinal disorders1/830/86
RENAL IMPAIRMENTRenal and urinary disorders1/830/86
URETHRAL HAEMORRHAGERenal and urinary disorders1/830/86
Most frequent other events
Most frequent other events
EventAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/Day
NASOPHARYNGITISInfections and infestations6/8312/86
DIARRHOEAGastrointestinal disorders8/8310/86
PYREXIAGeneral disorders7/8310/86
URINARY TRACT INFECTIONInfections and infestations9/836/86
CYSTITISInfections and infestations5/839/86
PHARYNGITISInfections and infestations8/835/86
RESPIRATORY TRACT INFECTIONInfections and infestations7/835/86
VOMITINGGastrointestinal disorders4/836/86
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations4/835/86

Baseline characteristics

Age, Continuous
Age, Continuous(years)PlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/DayTotal
Mean8.3 ± 4.47.9 ± 3.98.7 ± 3.98.3 ± 4.0
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/DayTotal
Female28273085
Male29302887
Region of Enrollment
Region of Enrollment(participants)PlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/DayTotal
United States67518
Portugal2136
Serbia46717
Taiwan0112
Estonia1113
Slovakia67114
Spain2327
Turkey1236
Russian Federation87419
India29920
France1247
Canada3126
Malaysia3003
Poland15101439
Germany3025
Urinary Tract Infection (UTI) history in the last 3 months
Urinary Tract Infection (UTI) history in the last 3 months(participants)PlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/DayTotal
No UTI episode485040138
One UTI episode851629
Two UTI episodes1225
Study drug formulation
Study drug formulation(participants)PlaceboAlfuzosin 0.1 mg/kg/DayAlfuzosin 0.2 mg/kg/DayTotal
Solution (2-7 years)28282884
Solution (8-16 years)810927
Tablets (8-16 years)21192161
08

Study locations

18 sites
  • Sanofi-Aventis Administrative Office
    Bridgewater, New Jersey 08807, United States
  • Sanofi-Aventis Administrative Office
    Sofia, Bulgaria
  • Sanofi-Aventis Administrative Office
    Laval, Canada
  • Sanofi-Aventis Administrative Office
    Tallinn, Estonia
  • Sanofi-Aventis Administrative Office
    Paris, France
  • Sanofi-Aventis Administrative Office
    Berlin, Germany
  • Sanofi-Aventis Administrative Office
    Mumbai, India
  • Sanofi-Aventis Administrative Office
    Kuala Lumpur, Malaysia
  • Sanofi-Aventis Administrative Office
    Makati City, Philippines
  • Sanofi-Aventis Administrative Office
    Warszawa, Poland
  • Sanofi-Aventis Administrative Office
    Porto Salvo, Portugal
  • Sanofi-Aventis Aministrative Office
    Moscow, Russian Federation
  • Sanofi-Aventis Administrative Office
    Belgrade, Serbia
  • Sanofi-Aventis Administrative Office
    Singapore, Singapore
  • Sanofi-Aventis Administrative Office
    Bratislava, Slovakia
  • Sanofi-Aventis Administrative Office
    Barcelona, Spain
  • Sanofi-Aventis Administrative Office
    Taipei, Taiwan
  • Sanofi-Aventis Administrative Office
    Istanbul, Turkey
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 29, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00549939
Lead sponsor
Sanofi
Responsible party
Sponsor
First posted
Oct 26, 2007
Start date
Oct 2007
Primary completion
Mar 2009
Completion
Dec 2009
Results posted
Feb 8, 2011
Last update
Oct 29, 2014

Study contacts

ICD CSD
study director · Sanofi

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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