RAPAFLO(TM) (silodosin) Provides Rapid And Sustained Benign Prostatic Hyperplasia (BPH) Symptom Relief In As Little As Three Days

Main Category: Prostate / Prostate Cancer
Also Included In: Clinical Trials / Drug Trials;  Pharma Industry / Biotech Industry
Article Date: 09 May 2009 - 1:00 PST

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RAPAFLO(TM) (silodosin), a new, uniquely selective alpha blocker for the treatment of the signs and symptoms of BPH, produces rapid improvements of both irritative and obstructive urinary symptoms that were sustained for 12 weeks, according to data published in the June issue of The Journal of Urology. RAPAFLO(TM) was developed and is manufactured by Watson Pharmaceuticals, a leader in generic and specialty branded pharmaceuticals.

In an analysis of data pooled from two Phase 3 studies, patients taking RAPAFLO(TM) demonstrated statistically significant symptom relief versus placebo within three to four days of starting treatment, and remained significant throughout the 12-week study period.

"The severity of urinary symptoms appears to depend in part on smooth muscle tone in the prostate and bladder neck, which is mediated by alpha 1A adrenoreceptors," said Leonard S. Marks, MD, author of the study and professor of urology at the Geffen School of Medicine, the University of California at Los Angeles. "The data indicate that RAPAFLO(TM) (silodosin) induces effective relaxation of the targeted prostatic muscle tissue, with a low incidence of vasodilatory and orthostatic effects. RAPAFLO(TM) (silodosin) is a fast acting, effective and safe treatment for the signs and symptoms associated with BPH."

BPH is the number one reason patients visit urologists and is characterized by urination problems, including decreased urine flow, more frequent urination and nocturia.

Clinical Trial Results

The new paper is a pooled analysis of two, 12-week, randomized, placebo-controlled, double-blind multi-center clinical trials involving 923 generally healthy men ages 50 or older with signs and symptoms of BPH, including a peak urine flow rate (Qmax) between 4 and 15 mL/sec (mean of 8.7 to 8.9) and International Prostate Symptom Score (IPSS) greater than or equal to 13 (mean of 21.3). IPSS includes irritative (frequency, urgency, and nocturia), and obstructive (hesitancy, incomplete emptying, intermittency, and weak stream) symptoms. Patients were randomized to either 8 mg RAPAFLO(TM) (n=466) or placebo (n=457) taken once daily with breakfast for 12 weeks.

The primary endpoint was change in IPSS from baseline to the last observation, including sub-scores related to irritative symptoms and obstructive symptoms. Change in peak urinary flow rate (Qmax scores) was a secondary endpoint.

At the last observation, patients treated with RAPAFLO(TM) versus placebo experienced significantly greater changes in total IPSS from baseline measures (-6.4 vs. -3.5, respectively; p<0.0001), as well as irritative (-2.3 vs. -1.4, respectively; p<0.0001) and obstructive (-4.0 vs. -2.1, respectively; p<0.0001) sub-scores. These differences were significantly better for RAPAFLO(TM) vs. placebo after three to four days of treatment (p<0.0001 for total IPSS and obstructive sub-score; p=0.0002 for irritative sub-score). RAPAFLO(TM) also significantly improved Qmax scores as early as two to six hours after the first dose and was sustained through 12 weeks of treatment.

The most common drug-related adverse event (AE) was retrograde ejaculation (orgasm with reduced semen), an expected treatment effect of selective alpha blockers, which occurred in 28 percent of men treated with RAPAFLO(TM). Retrograde ejaculation, a reversible treatment effect, led to treatment discontinuation in only 2.8 percent of patients, and does not pose a safety concern. Incidences of orthostatic hypotension among RAPAFLO(TM)- and placebo-treated patients were similar and low (2.6% and 1.5%, respectively). In addition, the incidence of treatment-related dizziness was only slightly higher among RAPAFLO(TM)- than placebo-treated patients (3.2% vs. 1.1%).

About RAPAFLO(TM)

RAPAFLO(TM) is an effective, uniquely selective alpha-1 adrenergic receptor antagonist. RAPAFLO(TM) maximizes target organ activity by binding with high affinity to the alpha (1A) receptors concentrated in the prostate. The antagonism of these receptors cause the smooth muscles in these tissues to relax and results in improved urine flow and a reduction in BPH symptoms. The binding affinity for the alpha (1B) receptors that cause smooth muscle in peripheral vessels is significantly lower, which may minimize orthostatic hypotension.

The most common drug-related side effect was retrograde ejaculation. The second most commonly-reported adverse event was dizziness. The incidence of treatment-related dizziness was low and only slightly higher among RAPAFLO(TM) than placebo-treated patients (11 vs. 3 patients).

Previously presented data included information that in clinical trials RAPAFLO(TM) was administered with a single dose of medications for erectile dysfunction in healthy male subjects (N=24) and that there were no reported events of symptomatic orthostasis or dizziness. RAPAFLO(TM) demonstrated no meaningful electro cardiac effects during Phase 3 trials and during thorough QTc testing as required for new chemical entities by the FDA.

RAPAFLO(TM) was originally developed by Kissei Pharmaceutical Co., Ltd. in Japan, where RAPAFLO(TM) is the BPH market leader, and licensed to Watson for the U.S., Canada and Mexico markets.

About Watson Pharmaceuticals, Inc.

Watson Pharmaceuticals, Inc. (NYSE: WPI) is a global leader in the development and distribution of pharmaceuticals with a broad portfolio of generic products and a specialized portfolio of branded pharmaceuticals focused on Urology, Gynecology and Nephrology (Medical).

In the U.S., the Watson portfolio includes RAPAFLO(TM), GELNIQUE(TM), TRELSTAR(R) LA; TRELSTAR(R) Depot; Ferrlecit(R), INFeD(R) and Oxytrol(R). In addition, Watson markets the following brands under co-promotion agreements: AndroGel(R), with Solvay Pharmaceuticals, Inc., and Femring(R), with Warner Chilcott Limited. The Watson pipeline portfolio includes a number of products, including a six-month formulation of TRELSTAR(R), for the treatment of advanced prostate cancer which is currently under review by the FDA; URACYST(R), under development for cystitis; and a novel new oral contraceptive.

Forward Looking Statement

Any statements contained in this press release that refer to future events or other non-historical facts are forward-looking statements that reflect Watson's current perspective of existing trends and information as of the date of this release. Except as expressly required by law, Watson disclaims any intent or obligation to update these forward-looking statements. Actual results may differ materially from Watson's current expectations depending upon a number of factors affecting Watson's business. These factors include, among others, the impact of competitive products and pricing; market acceptance of and continued demand for Watson's products, including RAPAFLO(TM); difficulties or delays in manufacturing; patents and other intellectual property rights held by the Company and the ability to successfully enforce such rights against third parties; and other risks and uncertainties detailed in Watson's periodic public filings with the Securities and Exchange Commission, including but not limited to Watson's Annual Report on Form 10-K for the year ended December 31, 2008.

Source: Watson Pharmaceuticals, Inc

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