Effect of silodosin on specific urinary symptoms associated with benign prostatic hyperplasia: analysis of international prostate symptom scores in 2 phase III clinical studies

Open Access Journal of Urology Dovepress open access to scientific and medical research O r i g i n al R e s e a r c h Research and Reports in Urology downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Open Access Full Text Article Effect of silodosin on specific urinary symptoms associated with benign prostatic hyperplasia: analysis of international prostate symptom scores in 2 phase III clinical studies This article was published in the following Dove Press journal: Open Access Journal of Urology 21 December 2010 Number of times this article has been viewed Marc C Gittelman 1 Leonard S Marks 2 Lawrence A Hill 3 Weining Volinn 3 Gary Hoel 3 1 South Florida Medical Research, Aventura, Florida, USA; 2University of California at Los Angeles and Urological Sciences Research Foundation, Los Angeles, California, USA; 3Watson Laboratories, Salt Lake City, Utah, USA Purpose: Pooled results from 2 randomized, placebo-controlled, US phase III studies (NCT00224107, NCT00224120) showed that silodosin, a uroselective α-blocker, significantly improved International Prostate Symptom Scores (IPSS) in men with symptomatic benign prostatic hyperplasia (BPH). This analysis evaluated the effect of silodosin on each symptom assessed by IPSS questionnaire. Materials and methods: Study participants (N = 923) were men aged $50 years with IPSS $13 and Qmax 4–15 mL/s. They received silodosin 8 mg or placebo once daily for 12 weeks. Patient responses to 7 IPSS questions were collected at weeks 0 (baseline), 0.5, 1, 2, 4, and 12 and scored on a 6-point scale. Efficacy of silodosin versus placebo was assessed by analysis of covariance. Results: For each symptom, the 2 treatment groups had similar mean baseline scores. Decrease in score from baseline (mean ± standard deviation) to last observation was significantly greater with silodosin than with placebo for all symptoms (P , 0.005); symptom improvement with silodosin (versus placebo) was greatest for weak stream (silodosin, −1.1 ± 1.4 versus placebo, −0.5 ± 1.2; P , 0.0001) and smallest for nocturia (silodosin, −0.6 ± 1.1 versus placebo, −0.4 ± 1.2; P = 0.0037). Compared with placebo, silodosin significantly improved nocturia within 1 week (silodosin, −0.5 ± 1.07 versus placebo, −0.3 ± 1.05; P = 0.009) and all other symptoms within 3 to 4 days (P , 0.01). Conclusions: Silodosin significantly improved all BPH-associated symptoms assessed by IPSS questionnaire within the first week of treatment. All improvements were maintained over the 12-week study period. Keywords: BPH, symptoms, rapid onset, silodosin, α1A-adrenoceptor antagonist Introduction Correspondence: Marc Gittelman South Florida Medical Research, 21st Century Oncology/UroMedixAventura Division, 21150 Biscayne Boulevard, Suite 300, Aventura, FL 33180, USA Tel +1 305-931-8080 Fax +1 305-931-7024 Email mgittelman@ southfloridamedicalresearch.com submit your manuscript | www.dovepress.com Dovepress DOI: 10.2147/OAJU.S15333 Powered by TCPDF (www.tcpdf.org) Benign prostatic hyperplasia (BPH) is a chronic condition often associated with lower urinary tract symptoms (LUTS). The severity of BPH-related LUTS appears to depend, at least in part, on smooth muscle tone in the prostate and bladder neck, which is mediated by α1A-adrenoceptors.1,2 α-Blockers (α1-adrenoceptor antagonists) have become the therapy of choice for patients with BPH-related LUTS because they provide effective symptom relief, are generally well tolerated, and are relatively inexpensive.3 However, α-blockers vary in their propensity to cause blood pressure-related adverse events, which have been attributed to the blockade of α1B-adrenoceptors in arterial vessels.2,4,5 Open Access Journal of Urology 2011:3 1–5 1 © 2011 Gittelman et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Dovepress Research and Reports in Urology downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Gittelman et al Silodosin is an α-blocker that recently has been approved in the United States (US) for treatment of the signs and symptoms of BPH. The pharmacological properties of silodosin are characterized by an exceptionally high selectivity for the α1A- versus α1B-adrenoceptor subtype.6,7 Moreover, silodosin has been shown to be highly selective for prostatic versus vascular tissue.8–10 Consistent with this observation, results from phase III clinical studies suggest that silodosin carries minimal risk for orthostatic hypotension and overall has excellent cardiovascular tolerability.11,12 Combined efficacy results from the phase III clinical studies showed that silodosin can promote rapid and significant improvement in BPH-associated urinary symptoms and peak urinary flow rate and can substantially improve LUTS-related quality of life.11 Overall symptom improvement was evaluated on the basis of aggregate patient scores for 7 distinct symptoms addressed by the International Prostate Symptom Score (IPSS) questionnaire. This post hoc analysis determined the effect of silodosin on each of the 7 symptoms. data for the primary efficacy variable (total IPSS) were included in the analysis; 466 patients received silodosin and 457 received placebo.11 The IPSS questionnaire assesses 7 distinct urinary symptoms. Frequency (question [Q2]), urgency (Q4), and nocturia (Q7) are classified as irritative symptoms. Incomplete emptying (Q1), intermittency (Q3), weak stream (Q5), and straining (Q6) are classified as obstructive symptoms. Severity of each symptom is scored on a 6-point scale.13 Mean changes in score from baseline with 95% confidence intervals (CIs) were calculated for observed cases at each time point. For additional analyses at week 12, the last post-baseline observation was carried forward to impute missing data. Comparison of treatment effects was performed by analysis of covariance (ANCOVA), with baseline as a covariate. No adjustments were made for multiple statistical comparisons. ANCOVA results were reported as P values (for the test of null hypothesis of no difference between treatments). A 2-sided significance level of 5% was applied to all statistical tests. Materials and methods Patients and study design Results This post hoc analysis of combined data from two 12-week randomized, double-blind, placebo-controlled US studies (NCT00224107, NCT00224120, at www.clinicaltrials. gov) evaluated the efficacy and safety of silodosin for the treatment of signs and symptoms of BPH. The study has been described in detail and overall results published.11 Briefly, study participants were at least 50 years of age with an IPSS greater than 13, a peak urinary flow rate (Qmax) of 4 to 15 mL/s, and a postvoid residual volume less than 250 mL. Patients first received single-blind treatment with placebo for 4 weeks. Those with at least (...truncated)