Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2004-002397-38 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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:
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:
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:
Patients who have completed the 12-week double-blind phase were offered to continue in the 40-week open-label extension study.
All patients had a one-week follow-up period after last dose intake.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Matching placebo 0.1 mg/kg/day or 0.2 mg/kg/day |
|
| Alfuzosin 0.1 mg/kg/day | Experimental |
| |
| Alfuzosin 0.2 mg/kg/day | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alfuzosin | Drug | Form: solution or tablet according to age Route: oral Dose: daily dose adjusted to body weight |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 12 weeks (double blind treatment period) |
| Measure | Description | Time Frame |
|---|---|---|
| Detrusor Leak Point Pressure (LPP) | Detrusor Leak Point Pressure (LPP) was assessed at baseline and 12 weeks as described for the primary outcome measure. | baseline and 12 weeks (double blind treatment period) |
| Absolute Change in Detrusor LPP |
Not provided
Inclusion Criteria:
Exclusion Criteria:
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| ICD CSD | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sanofi-Aventis Administrative Office | Bridgewater | New Jersey | 08807 | United States | ||
| Sanofi-Aventis Administrative Office |
172/261 patients were randomized in the 12-week double blind phase.
89/261 patients were not randomized for the following reasons:
'*' Patients could have several reasons.
The study was conducted at 55 sites in 18 countries. A total of 261 patients were screened between September 2007 and November 2008.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Alfuzosin 0.1 mg/kg/day matching placebo or Alfuzosin 0.2 mg/kg/day matching placebo |
| FG001 | Alfuzosin 0.1 mg/kg/Day | |
| FG002 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| 12-week Double Blind Treatment Period |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Drug | Form: matching solution or matching tablet according to age Route: oral Dose: daily dose adjusted to body weight |
|
Absolute change = Detrusor LPP at 12 weeks - Detrusor LPP at baseline
| 12 weeks ((double blind treatment period) |
| Relative Change in Detrusor LPP | Relative change = 100 * (Detrusor LPP at 12 weeks - Detrusor LPP at baseline) / Detrusor LPP at baseline | 12 weeks (double blind treatment period) |
| 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). | baseline and 12 weeks (double blind treatment period) |
| Relative Change in Detrusor Compliance | Relative change = 100 * (Detrusor compliance at 12 weeks - Detrusor compliance at baseline) / Detrusor compliance at baseline | 12 weeks (double blind treatment period) |
| 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. | 12 weeks (double blind treatment period) |
| 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. | 52 weeks (double blind treatment period + open label extension treatment period) |
| 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 | Warsaw | Poland |
| Sanofi-Aventis Administrative Office | Porto Salvo | Portugal |
| Sanofi-Aventis Aministrative Office | Moscow | Russia |
| 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 (Türkiye) |
| Alfuzosin 0.2 mg/kg/Day |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| 40-week Open Label Treatment Period |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Alfuzosin 0.1 mg/kg/day matching placebo or Alfuzosin 0.2 mg/kg/day matching placebo |
| BG001 | Alfuzosin 0.1 mg/kg/Day | |
| BG002 | Alfuzosin 0.2 mg/kg/Day | |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Urinary Tract Infection (UTI) history in the last 3 months | Number | participants |
| ||||||||||||||||
| Study drug formulation | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | The Intent-to-treat (ITT) population was used for the analysis. All randomized patients were included in the analysis in the treatment group to which they were allocated as per randomization. | Posted | Number | participants | 12 weeks (double blind treatment period) |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Detrusor Leak Point Pressure (LPP) | Detrusor Leak Point Pressure (LPP) was assessed at baseline and 12 weeks as described for the primary outcome measure. | The analysis was performed on the Intent-to-treat (ITT) population excluding the patients who didn't have baseline and/or post-baseline LPP values. Patients were included in the treatment group to which they were allocated as per randomization. | Posted | Mean | Standard Deviation | cmH2O | baseline and 12 weeks (double blind treatment period) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Absolute Change in Detrusor LPP | Absolute change = Detrusor LPP at 12 weeks - Detrusor LPP at baseline | The analysis was performed on the same population as previously (i.e. ITT population excluding the patients who didn't have baseline and/or post-baseline value). | Posted | Least Squares Mean | Standard Error | cmH2O | 12 weeks ((double blind treatment period) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Relative Change in Detrusor LPP | Relative change = 100 * (Detrusor LPP at 12 weeks - Detrusor LPP at baseline) / Detrusor LPP at baseline | The analysis was performed on the same population as previously (i.e. ITT population excluding the patients who didn't have baseline and/or post-baseline value). | Posted | Least Squares Mean | Standard Error | percentage of cmH2O | 12 weeks (double blind treatment period) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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). | The analysis was performed on the intent-to-treat (ITT) population excluding the patients who didn't have baseline and/or post baseline detrusor compliance values. Patients were included in the treatment group to which they were allocated as per randomization. | Posted | Mean | Standard Deviation | mL/cmH20 | baseline and 12 weeks (double blind treatment period) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Relative Change in Detrusor Compliance | Relative change = 100 * (Detrusor compliance at 12 weeks - Detrusor compliance at baseline) / Detrusor compliance at baseline | The analysis was performed on the same population as previously (i.e. ITT population excluding the patients who didn't have baseline and/or post-baseline value). | Posted | Least Squares Mean | Standard Error | percentage of mL/cmH2O | 12 weeks (double blind treatment period) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The analysis was performed on the intent-to-treat (ITT) population. All randomized patients were included in the analysis in the treatment group to which they were allocated as per randomization. | Posted | Number | participants | 12 weeks (double blind treatment period) |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The analysis was performed on the exposed population (i.e. all patients who received at least one dose of Alfuzosin regardless of the amount of treatment received). It included 3 + 3 patients treated during the 1st treatment period only, 26 + 28 patients treated during the 2nd treatment period only and 54 + 55 patients treated during both periods. | Posted | Number | participants | 52 weeks (double blind treatment period + open label extension treatment period) |
|
|
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.
The analysis was performed on the exposed population (i.e. all patients who received at least one dose of Alfuzosin, whatever the study period and regardless of the amount of treatment received) and included all AE that developed/worsened during the 'on treatment period' (i.e. from first dose up to 2 days after the last dose).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Alfuzosin 0.1 mg/kg/Day | 10 | 83 | 37 | 83 | |||
| EG001 | Alfuzosin 0.2 mg/kg/Day | 7 | 86 | 43 | 86 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| VIRAL INFECTION | Infections and infestations | MedDra 12.1 | Systematic Assessment |
| |
| PYELONEPHRITIS | Infections and infestations | MedDra 12.1 | Systematic Assessment |
| |
| PNEUMONIA | Infections and infestations | MedDra 12.1 | Systematic Assessment |
| |
| LOBAR PNEUMONIA | Infections and infestations | MedDra 12.1 | Systematic Assessment |
| |
| MALNUTRITION | Metabolism and nutrition disorders | MedDra 12.1 | Systematic Assessment |
| |
| EPILEPSY | Nervous system disorders | MedDra 12.1 | Systematic Assessment |
| |
| TETHERED CORD SYNDROME | Nervous system disorders | MedDra 12.1 | Systematic Assessment |
| |
| RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | MedDra 12.1 | Systematic Assessment |
| |
| TONSILLAR HYPERTROPHY | Respiratory, thoracic and mediastinal disorders | MedDra 12.1 | Systematic Assessment |
| |
| DECUBITUS ULCER | Skin and subcutaneous tissue disorders | MedDra 12.1 | Systematic Assessment |
| |
| RENAL IMPAIRMENT | Renal and urinary disorders | MedDra 12.1 | Systematic Assessment |
| |
| URETHRAL HAEMORRHAGE | Renal and urinary disorders | MedDra 12.1 | Systematic Assessment |
| |
| ARNOLD-CHIARI MALFORMATION | Congenital, familial and genetic disorders | MedDra 12.1 | Systematic Assessment |
| |
| FEMUR FRACTURE | Injury, poisoning and procedural complications | MedDra 12.1 | Systematic Assessment |
| |
| VENTRICULOPERITONEAL SHUNT MALFUNCTION | Injury, poisoning and procedural complications | MedDra 12.1 | Systematic Assessment |
| |
| CONTUSION | Injury, poisoning and procedural complications | MedDra 12.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| NASOPHARYNGITIS | Infections and infestations | MedDra 12.1 | Systematic Assessment |
| |
| CYSTITIS | Infections and infestations | MedDra 12.1 | Systematic Assessment |
| |
| URINARY TRACT INFECTION | Infections and infestations | MedDra 12.1 | Systematic Assessment |
| |
| PHARYNGITIS | Infections and infestations | MedDra 12.1 | Systematic Assessment |
| |
| RESPIRATORY TRACT INFECTION | Infections and infestations | MedDra 12.1 | Systematic Assessment |
| |
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDra 12.1 | Systematic Assessment |
| |
| DIARRHOEA | Gastrointestinal disorders | MedDra 12.1 | Systematic Assessment |
| |
| VOMITING | Gastrointestinal disorders | MedDra 12.1 | Systematic Assessment |
| |
| PYREXIA | General disorders | MedDra 12.1 | Systematic Assessment |
|
If no publication has occurred within 12 months after trial completion, the investigators can publish the results. Prior to publication, the sponsor shall review the manuscript and can request changes, provided they do not jeopardize the accuracy and/or the scientific value of the publication. The approval is given in writing by the sponsor, not to exceed 90 days.
To protect by a property right any information the sponsor can postpone the publication, for a period not to exceed 18 months.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi | Contact-US@sanofi.com |
| ID | Term |
|---|---|
| D001750 | Urinary Bladder, Neurogenic |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C047638 | alfuzosin |
Not provided
Not provided
Not provided
| Protocol Violation |
|
| Other |
|
| Male |
|
| Portugal |
|
| Serbia |
|
| Taiwan |
|
| Estonia |
|
| Slovakia |
|
| Spain |
|
| Turkey |
|
| Russian Federation |
|
| India |
|
| France |
|
| Canada |
|
| Malaysia |
|
| Poland |
|
| Germany |
|
| One UTI episode |
|
| Two UTI episodes |
|
| Solution (8-16 years) |
|
| Tablets (8-16 years) |
|
|
| 0.91 |
P-value was adjusted for multiplicity using the Hochberg procedure. The a priori threshold for statistical significance was 0.05. |
| No |
| Superiority or Other |
|
|
|
|
|
|
|
|
|
|