An Uncontrolled, Open-label, Titration, Long-term Safety (up to 12 Months) and Efficacy Study of Tamsulosin Hydrochloride in Children With Neuropathic Bladder, With a Randomized Pharmacokinetic Sub-study Investigating Low, Medium and High Dose Ranges.
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 143
- Primary Endpoint
- Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover.
Study Overview
Brief Summary
Aims of this study is to characterize the pharmacokinetic/pharmacodynamic profile and evaluate the safety, efficacy and tolerability, of tamsulosin hydrochloride as treatment in children with a neuropathic bladder, over the course of 12 months of active treatment.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 2 Years to 16 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Neuropathic bladder secondary to known neurological disorder
- •Elevated detrusor leak point pressures (LPP) ≥40 cm H2O confirmed by two measurements at baseline
Exclusion Criteria
- •Clinically significant abnormalities as determined by the investigator
- •A history of relevant orthostatic hypotension, fainting spells or blackouts
Arms & Interventions
1. Low dose group
Intervention: tamsulosin hydrochloride (Drug)
2. Medium dose group
Intervention: tamsulosin hydrochloride (Drug)
3. High dose group
Intervention: tamsulosin hydrochloride (Drug)
Outcomes
Primary Outcomes
Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover.
Time Frame: Week 1 (Visit 3) , Week 2 (Visit 4) , Week 3 (Visit 5) and Week 4 (Visit 6) prior to dose administration and Week 9 (Visit 7) (optional), Week 13 (Visit 8) (additional), Week 26 (Visit 9) (optional) and Week 52 (Visit 11) after drug administration.
Number of Leak point pressure (LPP) Responders at each visit (week) over time (classified by last value on treatment). Due to the early termination of the study, most of the LPP assessments were conducted within Weeks 1-9 of treatment. Summary of LPP response rates provided over time.The subjects are classified according to the treatment they were receiving at the last value on treatment. Therefore, no assumptions can be made regarding what dose they were receiving at a particular time point. LD: Low Dose, MD: Medium Dose and HD: High Dose This Outcome Measure was only pre-specified for Group D-527.51 Rollover subjects, so results of this group is provided.
Percentage of LPP Responders for Group D-Denovo and Group D-527.51 Rollover
Time Frame: Group D-Denovo: Week 52. Group D-527.51 Rollover: Week 1, Week 2, Week 3 and Week 4 prior to dose administration and Week9 (optional), Week 13 (additional), Week 26 (optional) and Week 52 after drug administration.
Group D-Denovo: Leak point pressure (LPP) Response at(response defined as a subject who achieves an LPP pressure \<40 cm H2O) at the end of treatment based on two confirmatory values. Group D-527.51 Rollover: Leak point pressure (LPP) Response at (response defined as a subject who achieves an LPP pressure \<40 cm H2O) last value of the treatment based on two confirmatory values. The last value on treatment included any final value prior to discontinuation of treatment, regardless of the length of treatment. Detrusor leak point pressure (LPP) recorded in cm H2O which was obtained using a standard urodynamic technique, a cystometrogram. Descriptive statistics were used to assess this endpoint. This Outcome Measure was only pre-specified for Group D-Denovo and Group D-527.51 Rollover subjects, so results of these two groups are provided.
Secondary Outcomes
- Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover(Group D-Denovo: Baseline and Week 52. Group D-527.51 Rollover: Baseline, Week 26 and Week 52.)
- Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse Events and Cognitive Testing for Group D-Denovo(From first drug administration until 28 days after last study drug administration, upto 450 days)
- Vision Testing for Group D-527.51 Rollover(Baseline and Week 52)
- Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover(Group D-Denovo: Baseline and Week 52. Group D-527.51 Rollover: Baseline, Week 26 and Week 52.)
- Tmax,ss(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)
- AUCτ ,ss ,DW ,Norm(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)
- t1/2,ss(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)
- CL/F,ss,W,Norm(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)
- Change From Baseline in LPP for Group D-527.51 Rollover(Baseline and week 1)
- Early Responders Who Maintained Their LPP Below 40 cm H2O During the Study for Group D-Denovo and Group D-527.51 Rollover(Week 1 to Week 52 (Time frame for all weeks are described study wise in the Description).)
- Percent Change From Baseline in LPP for Group D-527.51 Rollover(Baseline and Week 1)
- LPP Response at Any Time During the Trial for Group D-Denovo and Group D-527.51 Rollover(Week 1 to Week 52 (described study wise in the Description).)
- Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values,Urinalysis,Occurence of Adverse Events & Cognitive Testing for Group D-527.51 Rollover(From first drug administration until 28 days after last study drug administration, upto 395 days)
- Vision Testing for Group D-Denovo(Baseline, Week 26 and Week 52.)
- Cmax,1(-0.25h prior to dose and 2h, 4h, 6h and 8h after the drug administration.)
- λz,ss(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)
- Tmax, 1(-0.25h prior to dose and 2h, 4h, 6h and 8h after the drug administration.)
- Cpre,ss(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)
- Cmax,ss(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)
- MRTpo,ss(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)
- RA,Cmax(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)
- Cmax, 1 ,DW ,Norm(-0.25h prior to dose and 2h, 4h, 6h and 8h after the drug administration.)
- Cmin,ss(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)
- Cmax,ss, DW, Norm(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)
- AUCτ,ss(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)
- Vz/F,ss,W,Norm(-0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.)