Clinical Trial Results:
Four-Week, Open-Label, Multicenter, Randomized, Parallel-Group Study to Investigate the Pharmacokinetics, Safety, Tolerability and the Effects on Leak Point Pressure of 2 Oral Doses of Alfuzosin (0.1 mg/kg/day; 0.2 mg/kg/day) in Children and Adolescents 2 to 16 Years-of-Age with Elevated Detrusor Leak Point Pressure of Neuropathic Etiology
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Summary
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EudraCT number |
2014-004659-30 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
23 Feb 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Apr 2016
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First version publication date |
14 Jun 2015
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Other versions |
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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 |
PKM6270
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00629720 | ||
WHO universal trial number (UTN) |
- | ||
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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 & Developpement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi Aventis Recherche & Developpement, 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 |
09 Mar 2007
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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 |
23 Feb 2007
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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 investigate the pharmacokinetics (PK) of 2 doses of alfuzosin (0.1 and 0.2 mg/kg/day) given as a solution containing 0.2 mg/mL alfuzosin or as tablets containing 1.5 mg alfuzosin in children and adolescents 2 to 16 years-of-age with elevated detrusor leak point pressure (LPP) (≥40 cm H2O) of neuropathic etiology stratified into 2 age groups (2 to 7 years and 8 to 16 years).
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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 |
10 Jul 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Serbia: 24
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Country: Number of subjects enrolled |
United States: 5
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Worldwide total number of subjects |
29
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EEA total number of subjects |
0
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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) |
19
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Adolescents (12-17 years) |
10
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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 6 centers in 2 countries. A total of 45 subjects were screened between 10 July 2006 and 27 December 2006. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Of 45 screened subjects, 29 were randomized. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Alfuzosin 0.1 mg | ||||||||||||||||||
Arm description |
Alfuzosin 0.1 mg/kg/day for 4 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 |
Age group 2 - 7 years - alfuzosin solution 3 doses TID (thrice daily).
Age group 8 - 16 years - alfuzosin tablets 2 doses BID (twice daily).
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Arm title
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Alfuzosin 0.2 mg | ||||||||||||||||||
Arm description |
Alfuzosin 0.2 mg/kg/day for 4 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 |
Age group 2 - 7 years - alfuzosin solution 3 doses TID.
Age group 8 - 16 years - alfuzosin tablets 2 doses BID.
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Baseline characteristics reporting groups
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Reporting group title |
Alfuzosin 0.1 mg
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Reporting group description |
Alfuzosin 0.1 mg/kg/day for 4 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Alfuzosin 0.2 mg
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Reporting group description |
Alfuzosin 0.2 mg/kg/day for 4 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Alfuzosin 0.1 mg
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Reporting group description |
Alfuzosin 0.1 mg/kg/day for 4 weeks. | ||
Reporting group title |
Alfuzosin 0.2 mg
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Reporting group description |
Alfuzosin 0.2 mg/kg/day for 4 weeks. | ||
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End point title |
Alfuzosin Pharmacokinetics : Area Under The Plasma Concentration-Time Curve (AUC) from 0 up to 8 hours (AUC0-8) and AUC from 0 up to 12 hours (AUC0-12) [1] | ||||||||||||||||||||||||
End point description |
AUC was defined as area under the plasma concentration versus time curve extrapolated to infinity. AUC0-8 was defined as area under the curves calculated using the trapezoidal method from time zero (study medication intake) up to 8 hours (TID only). AUC 0-12 was defined as area under the curves calculated using the trapezoidal method from time zero (study medication intake) up to 12 hours (BID only).
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End point type |
Primary
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End point timeframe |
Day 1 and Day 7
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The purpose was to provide descriptive statistics only. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Change From Baseline in Detrusor LPP (cmH2O) at Week 4 | ||||||||||||
End point description |
The detrusor LPP was defined as the lowest detrusor pressure at which urine leakage occurred in the absence of either a detrusor contraction or increased abdominal pressure. Analysis was carried out on modified intent-to-treat (mITT) population defined as all randomized and treated subjects who had a baseline and at least one post-baseline LPP assessment.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 4
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Subjects With Any Treatment-Emergent Adverse Events (TEAEs) | |||||||||||||||
End point description |
TEAEs were defined as AEs that developed or worsened or became serious during the on-treatment portion of the study or within 2 days following the last administration of alfuzosin. Analysis was carried out on safety population defined as all subjects who were randomized and who received at least one dose of study medication.
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End point type |
Secondary
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End point timeframe |
Up to Week 4
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| No statistical analyses for this end point | ||||||||||||||||
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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 5) regardless of seriousness or relationship to investigational product.
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Adverse event reporting additional description |
Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the ‘on treatment period’ (the time from the first dose of investigational product up to 48 hours (included) after the last dose, which corresponds to 5 half-lives).
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
9.1
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Reporting groups
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Reporting group title |
Alfuzosin 0.1 mg : Solution (2-7 years)
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Reporting group description |
Alfuzosin solution (age group 2 - 7 years) 0.1 mg/kg/day for 4 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Alfuzosin 0.1 mg : Tablets (8-16 years)
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Reporting group description |
Alfuzosin tablets (age group 8 - 16 years) 0.1 mg/kg/day for 4 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Alfuzosin 0.2 mg : Solution (2-7 years)
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Reporting group description |
Alfuzosin solution (age group 2 - 7 years) 0.2 mg/kg/day for 4 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Alfuzosin 0.2 mg : Tablets (8-16 years)
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Reporting group description |
Alfuzosin tablets (age group 8 - 16 years) 0.2 mg/kg/day for 4 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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25 Aug 2006 |
1. To clarify and include additional explanations of the following protocol items: elevated detrusor LPP, urinary tract infection (UTI), and Tanner staging
2. To add 1 new exclusion criterion related to the study subjects’ safety that was established based on new practice guidelines and treatment recommendations for children with neuropathic bladder dysfunctions
3. To better characterize UTI in this study population, considering chronicity and recurrence of the problem and symptoms, because the protocol required including the subjects with a positive dipstick test for UTI. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
