Study to Evaluate the Efficacy and Safety of Tamsulosin in Children With Neurogenic Bladder

Study Overview
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Brief Summary
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Aim of this study is to evaluate the efficacy and safety of a range of doses of tamsulosin hydrochloride as treatment in children with an elevated detrusor leak point pressure associated with a known neurological deficit

Official Title
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A Phase IIb/III, Multi-centre, Double-blind, Randomised, Placebo-controlled, Dose Ranging Study of Tamsulosin Hydrochloride (Low, Medium and High Dose) as Treatment in Children With Neuropathic Bladder for Three Months

Conditions
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Bladder, Neurogenic

Intervention / Treatment
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* Drug: tamsulosin hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neuropathic bladder secondary to a known neurologic deficit (e.g. spina bifida) Elevated detrusor leak point pressures (LPP) ≥40 cm H2O confirmed by two measurements Exclusion Criteria: Clinically significant abnormalities as determined by the investigator A history of relevant orthostatic hypotension, fainting spells or blackouts

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received matching placebo to tamsulosin hydrochloride via opened capsules every day for 14 weeks | Drug: Placebo<br>* Oral<br>|
| Experimental: Low dose<br>Participants received 0.001 - 0.002 mg/kg tamsulosin hydrochloride via opened capsules every day for 14 weeks | Drug: tamsulosin hydrochloride<br>* Oral<br>* Other names: Omnic;|
| Experimental: Medium dose<br>Participants received 0.002 - 0.004 mg/kg tamsulosin hydrochloride via opened capsules every day for 14 weeks | Drug: tamsulosin hydrochloride<br>* Oral<br>* Other names: Omnic;|
| Experimental: High dose<br>Participants received 0.004 - 0.008 mg/kg tamsulosin hydrochloride via opened capsules every day for 14 weeks | Drug: tamsulosin hydrochloride<br>* Oral<br>* Other names: Omnic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to Treatment Defined as Patients Who Decrease Their Detrusor Leak Point Pressure (LPP) to <40 cm H2O Based Upon Two Evaluations on the Same Day. | The primary endpoint was response to treatment defined as patients who decreased their detrusor leak point pressure (LPP) based upon two evaluations on the same day to less than 40 cm H2O at Week 14 (end of treatment). Detrusor leak point pressure (LPP) recorded in cm H2O was obtained using a standard urodynamic technique, a cystometrogram. On treatment (OT): Consist of all on treatment data. Observations measured ≤3 days of stopping treatment was considered as on treatment. Missing data in these analyses was not replaced or imputed. | Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in LPP at Week 14 (End of Treatment) | Change from baseline in detrusor leak point pressure (LPP) at Week 14 (end of treatment) between each dose group and the placebo group was compared for the FAS-LPP. | Baseline and Week 14 | 
| Percentage Change From Baseline in LPP at Week 14 (End of Treatment) | Percent changes in detrusor leak point pressure (LPP) from baseline to the end of treatment at Week 14 between each dose group and the placebo group were compared for the FAS-LPP. | Baseline and Week 14. | 
| Response With Regard to Hydronephrosis Was Defined as Improvement or Stabilisation Based Upon the Renal Ultrasound Grading at Week 14 (End of Treatment) Compared to Baseline | Hydronephrosis response was defined as stabilisation or improvement of hydronephrosis measured by renal ultrasound at the end of treatment when compared to baseline, based on ultrasound grading. The lower or same grade at end of treatment compared to baseline is considered an improvement or stabilization | Baseline and Week 14 | 
| Response With Regard to Hydroureter Was Defined as Improvement or Stabilisation Based Upon the Renal Ultrasound at Week 14 (End of Treatment) Compared to Baseline | Hydroureter response was defined as stabilisation or improvement based on change from baseline in the presence or absence of hydroureter at the end of treatment (Week 14). Response defined as stabilization or improvement of hydroureter measured by renal ultrasound compared to baseline by treatment group (Patients are classified according to the treatment they were taking at Week 14 or end of treatment) at Week 14. | Baseline and Week 14 | 
| Change From Baseline in Urine Volume at Week 14 | Change in baseline urine volumes obtained by catheterisation as recorded in catheterisation diary at Week 14. | Baseline and Week 14 | 
| Change From Baseline in Number of Times Patient Was Wet at Catheterisation | Change from baseline in number of times patient was wet at time of catheterisation as recorded in catheterisation diary. | Baseline and Week 14 | 
| Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electorocardiogram (ECG), Laboratory Values, Urinalysis, Treatment Emergent AE's and Cognitive Testing. | Number of participants with Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic testing (blood pressure, pulse and respiratory rate), Electrocardiogram (ECG), Laboratory Values inclusive of hormonal assays, vision testing, Cognitive Testing, Occurrence of treatment emergent adverse events, Premature discontinuation of study drug due to AE and Urinalysis. Relevant findings or worsening of baseline conditions were reported as adverse events. | From first drug administration until 28 days after last study drug administration, upto 160 days | 
| Post Void Residual Volume at Week 14 | Median change from baseline to Week 14 in post void residual (mL) by study treatment. | Baseline and Week 14. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tamsulosin, pediatric, neurogenic bladder