10303

A Phase IIb/III, Multi-Center, Double-Blind, Randomized, Placebo Controlled, Dose Ranging Study of Tamsulosin Hydrochloride (low, medium and high dose) as Treatment in Children with Neuropathic Bladder for Three Months

Saturday, October 2, 2010: 3:51 PM
Yerba Buena Salon 9 (San Francisco Marriott Marquis)
Yves Homsy, MD, FAAP, FRCSC, Departments of Surgery and Pediatrics, Children's Urology Group, University of South Florida, Tampa, FL, Philip Arnold, Medical Affairs, Boehringer-Ingelheim Pharmaceuticals Inc, Ridgefield, CT and Wei Zhang, Biometrics, Boehringer-Ingelheim Pharmaceuticals Inc, Ridgefield, CT

Purpose: To evaluate the efficacy and safety of a range of doses of tamsulosin as treatment in children with an elevated detrusor leak point pressure (LPP) associated with neuropathic bladder

Methods:

Double-blind, randomized, placebo-controlled, dose ranging trial stratified by age (2-<5, 5-<10 and 10 – 16 years), concomitant use of anti-cholinergic medication and geographic region. 162 patients met eligibility criteria and 135 completed the 14-week study from Jan. 2008 to Feb. 2009. There was a 2-week dose-titration period following randomization during which patients were assigned to low, medium or high doses. All patients had LPP ≥40cm at entry and urodynamics were repeated at week 14. Renal ultrasound was at entry and at weeks 6 and 14.

Primary endpoint: Responders are defined as patients with a decrease of LPP to <40 cm H2O based upon two evaluations on the same day. 

Secondary endpoints included actual and percent change from baseline in LPP, improvement or stabilization of hydronephrosis/hydroureter and change in urine volumes obtained by catheterization and adverse events.

Results:

LPP Response: Of the 135 patients completing the study, 51 patients met the definition of LPP responder (LPP < 40 cm H2O) at week 14. There was no statistically significant difference for the response rates between each dose group and placebo.

                                 Response rates by treatment group at Week 14

                 Tamsulosin Dose

Placebo

Low

Medium

High

Number of Patients

34

25

33

33

LPP Responder N (%)

12 (35.3)

16 (45.7)

9 (27.3)

14 (42.4)

p-value

-----

0.53381

0.34301

0.52091

1 Dose group vs. Placebo

Mean change from baseline in LPP: The mean changes in LPP from baseline to Week 14 for the placebo, low, medium and high dose groups were -11.4, -17.6, -4.6 and -14.3 cm H2O, respectively.

Hydroureter/Hydronephrosis: The vast majority of patients showed either mild improvement or stabilization of hydroureter (96.5% for both kidneys) and hydronephrosis (92.9% for left kidney and 93.6% for right kidney).

Post-void residual values:There was no statistically significant decline in median post void residual volumes in any of the study groups at Week 14.

Safety results: Drug-related adverse events were reported by 2 (4.9%) placebo patients and 7 (5.8%) tamsulosin patients. There was 1 death (unknown cause) in the low dose tamsulosin group and 1 serious adverse event (shunt malfunction/hematoma) in the placebo group.

Conclusion:

Tamsulosin was not efficacious in pediatric patients with neuropathic bladder based on the results for all primary and secondary endpoints in this study. Tamsulosin was safe and well tolerated across all treatment groups.

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