Clinical Trial Results:
12-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to investigate the efficacy, pharmacodynamic and safety of two doses of alfuzosin (0.1 mg/kg/day; 0.2 mg/kg/day) in the treatment of children and adolescents 2 – 16 years of age with elevated detrusor leak point pressure of neuropathic etiology followed by a 40-week open-label extension
Summary
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EudraCT number |
2004-002397-38 |
Trial protocol |
FR PT DE ES PL EE SK BG |
Global end of trial date |
09 Dec 2009
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Results information
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Results version number |
v1 |
This version publication date |
01 Apr 2016
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First version publication date |
06 Dec 2014
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
EFC5722
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00549939 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Sanofi aventis recherche & développement
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Sponsor organisation address |
1 avenue Pierre Brossolette, Chilly-Mazarin , France, 91380
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Jan 2010
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Dec 2009
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
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 greater than or equal to (≥) 40 centimeter of water (cm H2O).
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Protection of trial subjects |
The study was conducted by investigators experienced in the treatment of pediatric subjects. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimize distress and discomfort.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Oct 2007
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 7
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Country: Number of subjects enrolled |
Portugal: 6
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Country: Number of subjects enrolled |
Spain: 7
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Country: Number of subjects enrolled |
Estonia: 3
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Country: Number of subjects enrolled |
Slovakia: 14
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Country: Number of subjects enrolled |
Poland: 39
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Country: Number of subjects enrolled |
United States: 18
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Country: Number of subjects enrolled |
Serbia: 17
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Country: Number of subjects enrolled |
Taiwan: 2
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Country: Number of subjects enrolled |
Turkey: 6
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Country: Number of subjects enrolled |
Russian Federation: 19
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Country: Number of subjects enrolled |
India: 20
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Country: Number of subjects enrolled |
Canada: 6
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Country: Number of subjects enrolled |
Malaysia: 3
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Country: Number of subjects enrolled |
Germany: 5
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Worldwide total number of subjects |
172
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EEA total number of subjects |
81
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
127
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Adolescents (12-17 years) |
45
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 55 sites in 18 countries. A total of 261 subjects were screened between September 2007 and November 2008. | ||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
172/261 subjects were randomized in the 12-week double blind phase. 89/261 subjects were not randomized for the following reasons: - Adverse event (1 subject*), - Inclusion/Exclusion criteria not met (69 subjects*), - Subject's request (11 subjects*), - Other (13 subjects*). '*' Subjects could have several reasons. | ||||||||||||||||||||||||||||
Period 1
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Period 1 title |
12-week efficacy phase
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Assessor | ||||||||||||||||||||||||||||
Blinding implementation details |
Subjects were randomized to either Alfuzosin 0.1 milligram per kilogram per Day (mg/kg/Day) or matching placebo 0.1 mg/kg/Day or Alfuzosin 0.2 mg/kg/Day or matching placebo 0.2 mg/kg/Day. Each placebo treatment matched the active drug treatment (tablet or solution) and was indistinguishable.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo - 12 weeks | ||||||||||||||||||||||||||||
Arm description |
Placebo (for Alfuzosin 0.1 mg/kg/Day) or placebo (for Alfuzosin 0.2 mg/kg/Day) for 12 weeks. | ||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral solution, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Either solution or tablet formulation depending on age;
The daily dose with solution was divided in 3 doses given at breakfast, lunch and dinner.
The daily dose with tablets was divided in 2 doses given at breakfast and dinner.
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Arm title
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Alfuzosin 0.1 mg/kg/Day - 12 weeks | ||||||||||||||||||||||||||||
Arm description |
Alfuzosin 0.1 mg/kg/Day for 12 weeks. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Alfuzosin
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Investigational medicinal product code |
SL770499
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Other name |
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Pharmaceutical forms |
Tablet, Oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Either solution or tablet formulation depending on age;
The daily dose with solution was divided in 3 doses given at breakfast, lunch and dinner.
The daily dose with tablet was divided in 2 doses given at breakfast and dinner.
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Arm title
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Alfuzosin 0.2 mg/kg/Day - 12 weeks | ||||||||||||||||||||||||||||
Arm description |
Alfuzosin, 0.2 mg/kg/Day for 12 weeks. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Alfuzosin
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Investigational medicinal product code |
SL770499
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Other name |
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Pharmaceutical forms |
Oral solution, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Either solution or tablet formulation depending on age;
The daily dose with solution was divided in 3 doses given at breakfast, lunch and dinner.
The daily dose with tablet was divided in 2 doses given at breakfast and dinner.
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Period 2
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Period 2 title |
40-week safety extension phase
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Alfuzosin 0.1 mg/kg/Day - 40 weeks extension | ||||||||||||||||||||||||||||
Arm description |
Alfuzosin 0.1 mg/kg/Day for 40 additional weeks open-label to subjects on Alfuzosin, 0.1 mg/kg/Day or on Placebo (for Alfuzosin, 0.1 mg/kg/Day) during the efficacy phase. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Alfuzosin
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Investigational medicinal product code |
SL770499
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Other name |
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Pharmaceutical forms |
Oral solution, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Same dosage and administration details as for the period 1.
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Arm title
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Alfuzosin 0.2 mg/kg/Day - 40 weeks extension | ||||||||||||||||||||||||||||
Arm description |
Alfuzosin 0.2 mg/kg/Day for 40 additional weeks open-label to subjects on Alfuzosin, 0.2 mg/kg/Day or on Placebo (for Alfuzosin, 0.2 mg/kg/Day) during the efficacy phase | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Alfuzosin
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Investigational medicinal product code |
SL770499
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Other name |
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Pharmaceutical forms |
Oral solution, Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Same dosage and administration details as for the period 1.
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Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: Subjects who completed the 12-week double-blind period had the possibility to continue in the 40-week open-label extension period or to stop. - 54/56 subjects in the placebo group switched to Alfuzosin 0.1 mg/kg/Day (26 subjects) or 0.2 mg/kg/Day (28 subjects) according to initial randomization; - 54/55 subjects in the Alfuzosin 0.1 mg/kg/Day continued; - 55/56 subjects in the Alfuzosin 0.2 mg/kg/Day continued. |
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Baseline characteristics reporting groups
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Reporting group title |
Placebo - 12 weeks
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Reporting group description |
Placebo (for Alfuzosin 0.1 mg/kg/Day) or placebo (for Alfuzosin 0.2 mg/kg/Day) for 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Alfuzosin 0.1 mg/kg/Day - 12 weeks
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Reporting group description |
Alfuzosin 0.1 mg/kg/Day for 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Alfuzosin 0.2 mg/kg/Day - 12 weeks
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Reporting group description |
Alfuzosin, 0.2 mg/kg/Day for 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo - 12 weeks
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Reporting group description |
Placebo (for Alfuzosin 0.1 mg/kg/Day) or placebo (for Alfuzosin 0.2 mg/kg/Day) for 12 weeks. | ||
Reporting group title |
Alfuzosin 0.1 mg/kg/Day - 12 weeks
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Reporting group description |
Alfuzosin 0.1 mg/kg/Day for 12 weeks. | ||
Reporting group title |
Alfuzosin 0.2 mg/kg/Day - 12 weeks
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Reporting group description |
Alfuzosin, 0.2 mg/kg/Day for 12 weeks. | ||
Reporting group title |
Alfuzosin 0.1 mg/kg/Day - 40 weeks extension
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Reporting group description |
Alfuzosin 0.1 mg/kg/Day for 40 additional weeks open-label to subjects on Alfuzosin, 0.1 mg/kg/Day or on Placebo (for Alfuzosin, 0.1 mg/kg/Day) during the efficacy phase. | ||
Reporting group title |
Alfuzosin 0.2 mg/kg/Day - 40 weeks extension
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Reporting group description |
Alfuzosin 0.2 mg/kg/Day for 40 additional weeks open-label to subjects on Alfuzosin, 0.2 mg/kg/Day or on Placebo (for Alfuzosin, 0.2 mg/kg/Day) during the efficacy phase | ||
Subject analysis set title |
Subjects Exposed to Alfuzosin 0.1 mg/kg/Day
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects who received at least one dose of Alfuzosin 0.1 mg/kg/Day during the overall study period (efficacy phase and/or safety extension phase) and regardless of the amount of treatment received.
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Subject analysis set title |
Subjects Exposed to Alfuzosin 0.2 mg/kg/Day
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects who received at least one dose of Alfuzosin 0.2 mg/kg/Day during the overall study period (efficacy phase and/or safety extension phase) and regardless of the amount of treatment received.
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End point title |
Number of Subjects With Detrusor LPP Less Than (<) 40 cm H2O at 12 Weeks | ||||||||||||||||||||
End point description |
Detrusor 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 third 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 (that is, endorsed by the Investigator taking into account reviewers opinion).
The Intent-to-treat (ITT) population was used for the analysis. All randomized subjects were included in the analysis in the treatment group to which they were allocated as per randomization.
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End point type |
Primary
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End point timeframe |
12 weeks (double blind treatment period)
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Statistical analysis title |
Alfuzosin 0.1 mg/kg/Day vs. Placebo | ||||||||||||||||||||
Comparison groups |
Placebo - 12 weeks v Alfuzosin 0.1 mg/kg/Day - 12 weeks
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Number of subjects included in analysis |
114
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 1 [1] | ||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||
Confidence interval |
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Notes [1] - P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05. |
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Statistical analysis title |
Alfuzosin 0.2 mg/kg/Day vs. Placebo | ||||||||||||||||||||
Comparison groups |
Placebo - 12 weeks v Alfuzosin 0.2 mg/kg/Day - 12 weeks
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Number of subjects included in analysis |
115
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.91 [2] | ||||||||||||||||||||
Method |
Fisher exact | ||||||||||||||||||||
Confidence interval |
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Notes [2] - P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05. |
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End point title |
Detrusor LPP at Baseline and 12 Weeks | ||||||||||||||||||||||||
End point description |
Detrusor LPP was assessed at baseline and 12 weeks as described for the primary outcome measure. The analysis was performed on the ITT population excluding the subjects who didn't have baseline and/or post-baseline LPP values. Subjects were included in the treatment group to which they were allocated as per randomization.
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End point type |
Secondary
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End point timeframe |
Baseline and 12 weeks
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No statistical analyses for this end point |
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End point title |
Absolute Change in Detrusor LPP at 12 Weeks | ||||||||||||||||
End point description |
Absolute change = Detrusor LPP at 12 weeks - Detrusor LPP at baseline.
LS Means were estimated using a 3-way analysis of covariance (ANCOVA) with treatment group (alfuzosin 0.1 mg/kg/day, alfuzosin 0.2 mg/kg/day or placebo), age/formulation group (2-7 years of age on solution, 8-16 years of age on solution or 8-16 years of age on tablets) and anticholinergic/antimuscarinic use (yes or no) as fixed effects, and centered baseline detrusor LPP as covariate. The analysis was performed on the ITT population excluding the subjects who didn't have baseline and/or post-baseline value).
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End point type |
Secondary
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End point timeframe |
Baseline and 12 weeks
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Statistical analysis title |
Alfuzosin 0.1 mg/kg/Day vs. Placebo | ||||||||||||||||
Comparison groups |
Alfuzosin 0.1 mg/kg/Day - 12 weeks v Placebo - 12 weeks
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Number of subjects included in analysis |
107
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Analysis specification |
Pre-specified
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Analysis type |
superiority [3] | ||||||||||||||||
P-value |
= 0.104 [4] | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
LS Mean difference versus Placebo | ||||||||||||||||
Point estimate |
-6.2
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-13.72 | ||||||||||||||||
upper limit |
1.29 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
3.8
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Notes [3] - Change in detrusor LPP was analyzed using a three-way analysis of covariance (ANCOVA) including 3 variables as fixed effects: - Treatment group (alfuzosin 0.1 mg/kg/day, alfuzosin 0.2 mg/kg/day or placebo), - Age/formulation group (2-7 years of age on solution, 8-16 years of age on solution or 8-16 years of age on tablets), - Anticholinergic/antimuscarinic use (yes or no), and using centered baseline detrusor LPP as covariate. [4] - P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05. |
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Statistical analysis title |
Alfuzosin 0.2 mg/kg/Day vs. Placebo | ||||||||||||||||
Comparison groups |
Placebo - 12 weeks v Alfuzosin 0.2 mg/kg/Day - 12 weeks
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Number of subjects included in analysis |
110
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.104 [5] | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
LS Mean difference versus Placebo | ||||||||||||||||
Point estimate |
-7.1
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-14.51 | ||||||||||||||||
upper limit |
0.39 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
3.77
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Notes [5] - P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05. |
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End point title |
Relative Change in Detrusor LPP at 12 Weeks | ||||||||||||||||
End point description |
Relative change = 100 * (Detrusor LPP at 12 weeks - Detrusor LPP at baseline) / Detrusor LPP at baseline.
LS Means were estimated using the same ANCOVA model as for Absolute Change in Detrusor LPP.
The analysis was performed on the ITT population excluding the subjects who didn't have baseline and/or post-baseline value.
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End point type |
Secondary
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End point timeframe |
Baseline and 12 weeks
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Statistical analysis title |
Alfuzosin 0.1 mg/kg/Day vs. Placebo | ||||||||||||||||
Comparison groups |
Placebo - 12 weeks v Alfuzosin 0.1 mg/kg/Day - 12 weeks
|
||||||||||||||||
Number of subjects included in analysis |
107
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority [6] | ||||||||||||||||
P-value |
= 0.1338 [7] | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
LS Mean difference versus Placebo | ||||||||||||||||
Point estimate |
-11.4
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-26.27 | ||||||||||||||||
upper limit |
3.53 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
7.54
|
||||||||||||||||
Notes [6] - Change in detrusor LPP was analyzed using a three-way analysis of covariance (ANCOVA) including 3 variables as fixed effects: - Treatment group (alfuzosin 0.1 mg/kg/day, alfuzosin 0.2 mg/kg/day or placebo), - Age/formulation group (2-7 years of age on solution, 8-16 years of age on solution or 8-16 years of age on tablets), - Anticholinergic/antimuscarinic use (yes or no), and using centered baseline detrusor LPP as covariate. [7] - P-values was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05. |
|||||||||||||||||
Statistical analysis title |
Alfuzosin 0.2 mg/kg/Day vs. Placebo | ||||||||||||||||
Comparison groups |
Placebo - 12 weeks v Alfuzosin 0.2 mg/kg/Day - 12 weeks
|
||||||||||||||||
Number of subjects included in analysis |
110
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.1152 [8] | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Parameter type |
LS Mean difference versus Placebo | ||||||||||||||||
Point estimate |
-14.3
|
||||||||||||||||
Confidence interval |
|||||||||||||||||
level |
95% | ||||||||||||||||
sides |
2-sided
|
||||||||||||||||
lower limit |
-29.1 | ||||||||||||||||
upper limit |
0.47 | ||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||
Dispersion value |
7.48
|
||||||||||||||||
Notes [8] - P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05. |
|
|||||||||||||||||||||||||
End point title |
Detrusor Compliance at Baseline and at 12 Weeks | ||||||||||||||||||||||||
End point description |
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).
The analysis was performed on the ITT population excluding the subjects who didn't have baseline and/or post baseline detrusor compliance values. Subjects were included in the treatment group to which they were allocated as per randomization.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and 12 weeks
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Relative Change in Detrusor Compliance at 12 Weeks | ||||||||||||||||
End point description |
Relative change = 100 * (Detrusor compliance at 12 weeks - Detrusor compliance at baseline) / Detrusor compliance at baseline
LS means were estimated using a 3-way analysis of covariance (ANCOVA) including treatment group (alfuzosin 0.1 mg/kg/day, alfuzosin 0.2 mg/kg/day or placebo), age/formulation group (2-7 years of age on solution, 8-16 years of age on solution or 8-16 years of age on tablets), anticholinergic/antimuscarinic use (yes or no) as fixed effects and centered baseline detrusor compliance as covariate.
The analysis was performed on the ITT population excluding the subjects who didn't have baseline and/or post-baseline value.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and 12 weeks
|
||||||||||||||||
|
|||||||||||||||||
Statistical analysis title |
Alfuzosin 0.1 mg/kg/Day vs. Placebo | ||||||||||||||||
Statistical analysis description |
Change in detrusor compliance was analyzed using a three-way analysis of covariance (ANCOVA) including 3 variables as fixed effects:
- Treatment group (alfuzosin 0.1 mg/kg/day, alfuzosin 0.2 mg/kg/day or placebo),
- Age/formulation group (2-7 years of age on solution, 8-16 years of age on solution or 8-16 years of age on tablets),
- Anticholinergic/antimuscarinic use (yes or no),
and using centered baseline detrusor compliance as covariate.
|
||||||||||||||||
Comparison groups |
Alfuzosin 0.1 mg/kg/Day - 12 weeks v Placebo - 12 weeks
|
||||||||||||||||
Number of subjects included in analysis |
106
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.7889 [9] | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [9] - P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05. |
|||||||||||||||||
Statistical analysis title |
Alfuzosin 0.2 mg/kg/Day vs. Placebo | ||||||||||||||||
Comparison groups |
Placebo - 12 weeks v Alfuzosin 0.2 mg/kg/Day - 12 weeks
|
||||||||||||||||
Number of subjects included in analysis |
109
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.7889 [10] | ||||||||||||||||
Method |
ANCOVA | ||||||||||||||||
Confidence interval |
|||||||||||||||||
Notes [10] - P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05. |
|
|||||||||||||||||||||||||
End point title |
Number of Subjects With Symptomatic UTI Episodes During the First 12 Weeks | ||||||||||||||||||||||||
End point description |
When a subject 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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
12 weeks (double blind treatment period)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of Subjects With Symptomatic UTI Episodes During the Overall Study Period | ||||||||||||||||||||||||
End point description |
The analysis was performed on the safety population (that is, all subjects who received at least one dose of Alfuzosin regardless of the amount of treatment received). It included 3 + 3 subjects treated during the 1st treatment period only, 26 + 28 subjects treated during the 2nd treatment period only and 54 + 55 subjects treated during both periods.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
52 weeks (12 plus 40 weeks)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product.
|
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Adverse event reporting additional description |
Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the ‘on treatment period’ (time from first dose of alfuzosin [study Day 1 for subjects who took alfuzosin during the double-blind phase and Week 12 for subjects who took placebo during the double-blind phase] to last dose of alfuzosin plus 48 hours [5 half lives]).
|
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.1
|
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Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Alfuzosin 0.1 mg/kg/Day
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Alfuzosin 0.1 mg/kg/Day tablet or solution orally for 52 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Alfuzosin 0.2 mg/kg/Day
|
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Reporting group description |
Alfuzosin 0.2 mg/kg/Day tablet or solution orally for 52 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
25 Sep 2007 |
Modification of several aspects of the original protocol in order to define an exclusion criterion related to the study drug more precisely, to provide more details on the formulations used in the study, to change the PK sampling schedule, to better characterize the assessment of vital signs, and to revise the time window for cystometry. |
||
06 Oct 2008 |
Modifications of the PK sampling schedule for subjects randomized after 31 August 2008, revision of the temporary treatment discontinuation procedure and characterization of the collection of laboratory results in more detail. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |