Watson Pharmaceuticals Announces New Research Showing RAPAFLO (silodosin) Improves Outcomes for Chronic Prostatitis

Watson Pharmaceuticals Announces New Research Showing RAPAFLO(R) (silodosin) Improves Outcomes for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

- Treatment Reduces Symptoms and Improves Quality of Life -

- RAPAFLO(R) demonstrated significant response in men with moderate to severe CP/CPPS -

WASHINGTON, May 17, 2011 /PRNewswire/ -- New data presented today show that RAPAFLO(R) (silodosin) significantly reduced symptoms of moderate to severe chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).  In the study presented at the annual meeting of the American Urological Association, RAPAFLO(R) also significantly improved urinary symptoms as well as quality of life.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition characterized by persistent discomfort in the lower pelvic area and can have significant impact on quality of life. Symptoms can be severe and include painful and frequent urination and difficult or painful ejaculation. By definition, this type of prostatitis is not associated with a bacterial infection, and the cause is unknown. As many as 10 percent of men in North America have had or will have experienced prostatitis symptoms, and 90 percent of them have CP/CPPS. Evaluated in this trial for CP/CPPS, RAPAFLO(R) is a uniquely selective alpha blocker approved for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH), commonly referred to as an enlarged prostate.

"In this well-controlled, double-blind study, RAPAFLO(R) has demonstrated significantly improved outcomes in men suffering from CP/CPPS," said J. Curtis Nickel, M.D., urologist at Kingston General Hospital and Professor of Urology at Queen's University in Kingston, Ontario, Canada, and lead author of the study. "Importantly, twice as many men treated with RAPAFLO 4 mg once daily versus placebo reported feeling a moderate to marked improvement in their condition, showing that the statistically significant findings also were clinically meaningful for the patients."

Study Results

In this Phase 2 study with 151 patients, compared with placebo, RAPAFLO(R) at a 4 mg dose significantly decreased the total score on the well-recognized National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scale, which measures symptoms and impact on quality of life (-12.1 +/- 9.3 vs. -8.5 +/- 7.2; P=0.0224).  Statistically significant treatment effects were seen with RAPAFLO(R) 4 mg on the NIH-CPSI scale evaluating urinary symptoms (-2.2 +/- 2.7 vs -1.3 +/- 3.0; P=.0102). Decreases in NIH-CPSI scores with RAPAFLO(R) 8 mg did not provide any additional therapeutic benefit compared to the 4 mg dose. 

In addition, patients treated with RAPAFLO(R) 4 mg showed significantly better results relative to placebo on the physical component of another widely accepted evaluation tool, the 12-Item Short Form Health Survey (SF-12) developed to study patients with chronic conditions (4.2 +/- 8.1 vs 1.7 +/- 9.0; P=.049). In a global response assessment (GRA), 56 percent of patients treated with RAPAFLO(R) 4 mg versus 29 percent of patients receiving placebo reported moderate or marked improvement (P= 0.0069). An increase in dose to 8 mg resulted in no incremental increased effect.

Safety Findings

Overall, one in three (33.1%) of men in the study experienced a treatment-related adverse event (AE).  The incidences of drug-related AEs were similar for RAPAFLO(R) 4 mg and placebo, and included: dizziness (1.9%, 4 mg; 8.9%, 8 mg; 7.4%, placebo);  headache (0, 4 mg; 4.4%, 8 mg; 1.9%, placebo); nasal congestion (3.8%, 4 mg; 6.7%, 8 mg; 0, placebo); and decreased libido (1.9%, 4 mg; 2.2%, 8 mg; 1.9%, placebo).  The most common adverse event was retrograde ejaculation.  More men treated with RAPAFLO(R) versus placebo experienced retrograde ejaculation (26.9%, 4 mg; 40%, 8 mg; 1.9%, placebo).  Retrograde ejaculation, or an orgasm with reduced semen, is an expected and reversible effect of selective alpha blockers and thought to be a direct reflection of the product's selective binding properties.  Discontinuation rates due to a drug-related adverse event were 5.8 percent for RAPAFLO(R) 4 mg, 13.3 percent for RAPAFLO(R) 8 mg, and 1.9 percent for placebo.

Study Design

The double-blind, 12-week, placebo-controlled Phase 2 study evaluated the safety and efficacy of RAPAFLO(R) in patients with moderate to severe non-bacterial CP/CPPS who previously had not received alpha-blockers for the condition.  Patients with National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score >/=15 (moderate to severe), NIH-CPSI pain score >/=8 (mild to moderate), and pelvic pain for >/=3 months before screening were randomized to RAPAFLO(R) 4 mg or 8 mg per day, or placebo. The primary measure of efficacy was improvement in the NIH-CPSI total score. Of 151 participants, 76.2 percent completed the study. The median age of patients was 48.2 years; 80.1 percent had experienced pain for at least one year.

Secondary end points evaluated were: safety; change from baseline in NIH-CPSI pain, urinary, and quality of life scores; and change from baseline in Medical Outcomes Study Short Form 12 (SF-12) physical and mental component scores. Additional secondary end points were percentages of participants who had a sufficiently significant decrease in total score (NIH-CPSI responders) and of those who indicated "markedly improved" or "moderately improved" on the global response assessment (GRA) scale (GRA responders).

About RAPAFLO(R) (silodosin)

RAPAFLO(R) was first approved by the FDA two years ago for the treatment of signs and symptoms of benign prostatic hyperplasia (BPH). 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 cause smooth muscle in peripheral vessels is significantly lower, which may minimize orthostatic hypotension.

The most common drug-related side effect was retrograde ejaculation, or orgasm with reduced semen, which is reversible upon discontinuation of the product. The second most commonly-reported adverse event was dizziness. The incidence of treatment-related dizziness was low and only slightly higher among patients treated with RAPAFLO(R) than placebo-treated patients.

Previously presented data included information that in clinical trials RAPAFLO(R) was administered concomitantly with a single dose of medications for erectile dysfunction in healthy male subjects (N=24) and that there were no reported events of symptomatic orthostatis or dizziness. 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 is licensed to Watson for the U.S., Canada and Mexico markets.

Important Safety Information

RAPAFLO(R) is contraindicated in patients with severe renal impairment (CCr <30 mL/min), severe hepatic impairment (Child-Pugh score >/=10), and with use of strong CYP3A4 inhibitors. Postural hypotension with or without symptoms (eg, dizziness) may develop when beginning treatment with RAPAFLO(R). As with all alpha-blockers, there is a potential for syncope. Patients should be warned of the possible occurrences of such events and should avoid situations where injury could result. RAPAFLO(R) should be used with caution in patients with moderate renal impairment. Patients should be assessed to rule out the presence of prostate cancer prior to starting treatment with RAPAFLO(R). Patients planning cataract surgery should inform their ophthalmologist that they are taking RAPAFLO(R).

The most common side effects are retrograde ejaculation, dizziness, diarrhea, orthostatic hypotension, headache, nasopharyngitis, and nasal congestion.

About Watson Pharmaceuticals

Watson Pharmaceuticals, Inc. is a leading integrated global 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 many of the world's established and growing international markets.

For press release and other company information, visit Watson Pharmaceuticals' Web site at http://www.watson.com.