- Secondary trial endpoint reinforces prior, positive, sustained efficacy data -
CORONA, Calif., Dec 09, 2009 /PRNewswire-FirstCall via COMTEX/ -- Watson Pharmaceuticals, Inc. (NYSE: WPI) today announced that the results of an open-label extension of two Phase 3 studies, published in the December issue of the peer-reviewed journal Urology, demonstrate long-term safety and tolerability of RAPAFLO(R) (silodosin) for up to 52 weeks of treatment. RAPAFLO(R) is an effective and uniquely selective alpha blocker for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH), the number one reason patients visit urologists.
RAPAFLO(R) was shown to be well tolerated and safe throughout the one year study with low incidences of dizziness and orthostatic hypotension (drop in blood pressure upon standing). In addition, there were no serious, drug-related adverse events (AEs) reported during the study. A secondary endpoint demonstrated that RAPAFLO(R) significantly reduced BPH symptoms, as measured by International Prostate Symptom Score (IPSS), from baseline (week 12 of treatment) through week 52 in men who switched from placebo to RAPAFLO(R) in the open-label phase as well as in men continuing active treatment from the Phase 3 studies.
The patients enrolled in the 9-month, open-label extension had completed one of two identical 12-week, randomized, placebo-controlled, double-blind multi-center clinical trials. A total of 661 patients who completed the trials were enrolled in the extension.
"Relief of urinary symptoms in BPH patients is, in part, mediated by alpha 1A adrenoreceptors. First-generation alpha blockers are nonselective with regard to alpha 1 adrenoreceptor subtypes and, as a result, have been associated with orthostatic hypotension," 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. "RAPAFLO(R) has a uniquely selective profile that delivers sustained BPH symptom relief to patients with an excellent cardiovascular safety profile."
BPH is characterized by urination problems, including decreased urine flow, more frequent urination and nocturia.
Clinical Trial Results
Patients participating in the trial were men ages 50 or older with signs and symptoms of BPH, including a peak urine flow rate (Qmax) between 4 and 15 mL/sec and IPSS greater than or equal to 13. IPSS includes irritative (frequency, urgency, and nocturia), and obstructive (hesitancy, incomplete emptying, intermittency, and weak stream) symptoms. In the open-label phase, all participants received RAPAFLO(R) 8 mg.
The primary endpoint was safety over 9 months (from weeks 12 to 52) based on reported AEs, vital signs assessments, electrocardiograms, clinical laboratory tests, and physical examinations. Changes in IPSS and quality of life also were measured at baseline (week 12) and at 40 weeks (the end of the 52-week period) in patients who had previously received placebo during the 12 weeks of the phase III trials (de novo treatment) and in those who had originally been randomized to RAPAFLO(R) (continuing treatment) in the Phase 3 trials.
Overall, 65 percent of patients (431 of 661) experienced a total of 924 AEs; about 28 percent of these events (experienced by 188 patients) were considered to be drug-related. The majority of AEs were mild to moderate in severity. None of the severe AEs were considered to be drug-related.
The most common drug-related AE was retrograde ejaculation (orgasm with reduced semen), an expected treatment effect of selective alpha blockers, which occurred in 20.9 percent of men treated with RAPAFLO(R). Retrograde ejaculation is reversible upon discontinuation of the drug. Discontinuation rates due to AEs, including retrograde ejaculation, were significantly higher among men in the de novo treatment group versus men continuing treatment.
On efficacy measures, patients in the continuing treatment group had substantially lower baseline IPSS values than did patients in the de novo treatment group. IPSS values decreased significantly from baseline to week 52 in both treatment groups (mean change: -4.5 for de novo treatment and -1.6 for continuing treatment). In addition, patients who were "mostly satisfied," "pleased," or "delighted" with treatment increased from the start of the open-label study to the end of the trial in both groups (from 21.3% to 37.5%, de novo treatment; from 33.8% to 42.0%, continuing treatment).
RAPAFLO(R) is an effective, uniquely selective alpha-1 adrenergic receptor antagonist. RAPAFLO(R) 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 are in the smooth muscle in peripheral vessels is significantly lower, which may minimize orthostatic hypotension. There is moderate affinity to alpha (1D) receptors which are located in the bladder, spinal cord, and nasal passages and thought to play a role in bladder symptoms and regulate nasal secretions.
The most common drug-related side effect in pivotal clinical trials was retrograde ejaculation. The second most commonly-reported adverse event was dizziness. The incidence of treatment-emergent dizziness was low and only slightly higher among RAPAFLO(R) than placebo-treated patients (3.2% vs. 1.1% of patients).
Previously presented data included information that in clinical trials RAPAFLO(R) was administered with a single dose of medications commonly used for erectile dysfunction (tadalafil and sildenafil) in healthy male subjects (N=24) and that there were no reported events of symptomatic orthostasis or dizziness. Caution should be used when using these products concomitantly. RAPAFLO(R) 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(R) was originally developed by Kissei Pharmaceutical Co., Ltd. in Japan, where RAPAFLO(R) 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 leading global specialty pharmaceutical company. The Company is engaged in the development and distribution of generic pharmaceuticals and specialized branded pharmaceutical products focused on Urology and Women's Health. Watson has operations in over 20 countries including many of the world's established and growing international markets.
In the U.S., the Watson portfolio includes RAPAFLO(R), GELNIQUE(R), Oxytrol(R), TRELSTAR(R) LA; TRELSTAR(R) Depot; Ferrlecit(R), and INFeD(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.
For press releases and other company information, visit the Watson Web site at http://www.watson.com.
Statements contained in this press release that refer to Watson's estimated or anticipated future results 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. For instance, any statements in this press release concerning prospects related to Watson's strategic initiatives, product introductions and anticipated financial performance are forward-looking statements. It is important to note that Watson's goals and expectations are not predictions of actual performance. Watson's performance, at times, will differ from its goals and expectations. 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 inherent uncertainty associated with financial projections; successful integration of the Arrow acquisition and the ability to recognize the anticipated synergies and benefits of the Arrow acquisition; the impact of competitive products and pricing; the difficulty of predicting the timing or outcome of litigation; variability of revenue mix between the Company's Brand, Generic and Distribution business units; periodic dependence on a small number of products for a material source of net revenue or income; variability of trade buying patterns; changes in generally accepted accounting principles; risks that the carrying values of assets may be negatively impacted by future events and circumstances; timely and successful consummation and implementation of strategic initiatives; the timing and success of product launches; the difficulty of predicting the timing or outcome of product development efforts and FDA or other regulatory agency approvals or actions; the uncertainty associated with the identification and successful consummation of external business development transactions; market acceptance of and continued demand for Watson's products; costs and efforts to defend or enforce intellectual property rights; difficulties or delays in manufacturing; the availability and pricing of third party sourced products and materials; successful compliance with FDA and other governmental regulations applicable to Watson's and its third party manufacturers' facilities, products and/or businesses; uncertainties related to the timing and outcome of litigation and other claims; changes in the laws and regulations, including Medicare and Medicaid, affecting among other things, pricing and reimbursement of pharmaceutical products; and such other risks and uncertainties detailed in Watson's periodic public filings with the Securities and Exchange Commission, including but not limited to Watson's quarterly report on Form 10-Q for the period ended September 30, 2009. Except as expressly required by law, Watson disclaims any intent or obligation to update these forward-looking statements.
SOURCE Watson Pharmaceuticals, Inc.