Tamsulosin oral controlled absorption system (OCAS) in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH):: Efficacy and tolerability in a placebo and active comparator controlled phase 3a study

Objectives: This phase 3a study assessed the efficacy and safety of two different doses of a new formulation of tamsulosin (the oral controlled absorption system: OCAS) in comparison with placebo and the old modified release (MR) formulation of tamsulosin. Methods: After a two-week single-blind, placebo run-in period, older men (greater than or equal to45 years) with lower urinary tract symptoms (LUTS: total International Prostate Symptom Score (I-PSS) greater than or equal to13) suggestive of benign prostatic hyperplasia (BPH: maximum flow rate 4-12 ml/s) were randomised to 12 weeks of treatment with placebo, tamsulosin OCAS 0.4 mg, tamsulosin OCAS 0.8 mg or tamsulosin MR 0.4 mg once daily in a 1: 1:2:2 ratio. The primary efficacy variable was the mean change from baseline to endpoint in total I-PSS. Tolerability was mainly assessed by documenting adverse events (AEs) reported by the patient and vital signs. Results: A total of 2152 patients were randomised to placebo (N = 357), tamsulosin OCAS 0.4 mg (N = 36 1), tamsulosin MR 0.4 mcy (N = 710) or tamsulosin OCAS 0.8 mg (N = 724). For the mean reduction in total I-PSS from baseline to endpoint, there was no statistically significant difference between tamsulosin OCAS 0.8 mg (8.0 points or 42.4%) and tamsulosin MR 0.4 mg (8.0 points or 43.2%; p = 0.9909). Both tamsulosin OCAS 0.4 mg (7.7 points or 41.7%) and tamsulosin MR 0.4 mg were similarly superior to placebo (5.8 points or 32.0%; P < 0.0001 for both comparisons). The same observations were found for the improvement in the patient's urinary condition, both in the opinion of the patients and investigators. The two most frequently reported AEs were those commonly associated with alpha(1)-adrenoceptor (AR) antagonists: dizziness and abnormal ejaculation. The incidence of dizziness was comparable for the 0.4 mg dose (1.4%) and placebo (1.4%) and increased slightly with tamsulosin MR 0.4 mg (1.7%) and tamsulosin OCAS 0.8 mg (2.4%) although none of the comparisons was statistically significant. However, the incidence of abnormal ejaculation more clearly increased from tamsulosin OCAS 0.4 mg (1.9%) to tamsulosin MR (3.1%) and tamsulosin OCAS 0.8 mg (5.3%). Furthermore, whereas the incidence of abnormal ejaculation for tamsulosin MR 0.4 mg and tamsulosin OCAS 0.8 mg was statistically significantly higher than with placebo (0.3%), the difference between tamsulosin OCAS 0.4 mg and placebo was not statistically significant. Tamsulosin OCAS 0.4 mg had the lowest incidence of those AEs attributable to alpha(1)-AR antagonists and was also associated with the smallest reduction in blood pressure. Conclusions: Tamsulosin OCAS 0.8 mg is not superior to tamsulosin MR 0.4 mg and is associated with a higher incidence of AEs. Therefore, 0.4 mg is the recommended dose of tamsulosin OCAS in the treatment of patients with LUTS/BPH. The efficacy of tamsulosin OCAS 0.4 mg is superior to placebo and comparable to tamsulosin MR 0.4 mg with a tendency towards a better efficacy/tolerability ratio than with tamsulosin MR 0.4 mg. (C) 2004 Elsevier B.V. All rights reserved.