New Published Data Demonstrate Long-Term Safety, Efficacy and Tolerability of Watson’s RAPAFLO(R) (silodosin) for Benign Prostatic Hyperplasia (BPH) Symptom Relief
CORONA, Calif., Dec. 9 /PRNewswire-FirstCall/ — 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 RAPAFLOÂ® (silodosin) for up to 52 weeks of treatment. RAPAFLOÂ® 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.
RAPAFLOÂ® 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 RAPAFLOÂ® 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 RAPAFLOÂ® 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. “RAPAFLOÂ® 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 RAPAFLOÂ® 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 RAPAFLOÂ® (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 RAPAFLOÂ®. 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).
RAPAFLOÂ® is an effective, uniquely selective alpha-1 adrenergic receptor antagonist. RAPAFLOÂ® 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 RAPAFLOÂ® than placebo-treated patients (3.2% vs. 1.1% of patients).
Previously presented data included information that in clinical trials RAPAFLOÂ® 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. RAPAFLOÂ® demonstrated no meaningful electro cardiac effects during Phase 3 trials and during thorough QTc testing as required for new chemical entities by the FDA.
RAPAFLOÂ® was originally developed by Kissei Pharmaceutical Co., Ltd. in Japan, where RAPAFLOÂ® 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 RAPAFLOÂ®, GELNIQUEÂ®, OxytrolÂ®, TRELSTARÂ® LA; TRELSTARÂ® Depot; FerrlecitÂ®, and INFeDÂ®. In addition, Watson markets the following brands under co-promotion agreements: AndroGelÂ®, with Solvay Pharmaceuticals, Inc., and FemringÂ®, with Warner Chilcott Limited. The Watson pipeline portfolio includes a number of products, including a six-month formulation of TRELSTARÂ®, for the treatment of advanced prostate cancer which is currently under review by the FDA; URACYSTÂ®, under development for cystitis; and a novel new oral contraceptive.
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SOURCE Watson Pharmaceuticals, Inc.