Urological Sciences Research Foundation Release: A Study Published In Urology Reports Uroxatral(R) Offers Early Effects In Relieving Urinary Symptoms Associated With Enlarged Prostate

CULVER CITY, Calif., Dec. 9 /PRNewswire/ -- The study, which appears in the November 2003 issue of Urology showed significant improvement of the urine flow eight hours after the first dose of the prescription drug Uroxatral(R) (10 mg once daily). This effect was confirmed following three days of continuous therapy.

(LOGO: http://www.newscom.com/cgi-bin/prnh/20031209/NYTU045 )

According to Leonard S. Marks, M.D., medical director of Urological Sciences Research Foundation where the study was conducted and lead author of the paper, the study is important because little was known about the efficacy of Uroxatral(R) and similar drugs (called alpha(1)-blockers) during the first hours or days after the initial dose -- despite the fact that they are the most commonly prescribed drugs for men with symptomatic benign prostatic hyperplasia (BPH), a non-cancerous enlargement of the prostate.

"Alpha(1)-blockers are effective medications for relieving the symptoms of BPH, but information is lacking about their early effects because initial dosing is typically done at home, without medical supervision. This study was designed to assess the effect of Uroxatral(R) in men within hours of the first administration," Dr. Marks said. "Our findings showed that Uroxatral significantly increased urine flow as early as eight hours after the initial dose, and the incidence of side effects was low."

Non-cancerous enlargement of the prostate, which affects more than 8 million men in the United States, is a progressive condition that causes urinary symptoms, such as frequent and urgent need to urinate during the day and night, decreased urinary flow and weak urinary stream. More than half of all men over age 60 suffer from BPH, and after age 80, men have an 80 percent change of developing the condition.(i) If left untreated, BPH can lead to serious health problems, including urinary tract infections, bladder and kidney damage, bladder stones, incontinence, and acute urinary retention.

About the study

The study, known as the ALFIRST Trial, was a randomized, placebo- controlled, two-way Latin square crossover study designed to evaluate the onset of action of Uroxatral(R) as determined by peak urinary flow rate early after initial dosing. Forty-nine men, aged 50 and older, were selected to participate based on previous treatment success with alpha(1)-blockers and a subsequent recurrence of urinary symptoms following treatment cessation. Patients were randomly assigned to receive either Uroxatral(R) 10 mg or a placebo for seven days. After a seven-day placebo washout phase, patients were then crossed over to the alternative therapy, whereby they received the reverse treatment sequence for seven days.

The primary objective was to determine the effect of a single dose of alfuzosin on peak urinary flow rate. Secondary objectives included the effect on the maintenance or improvement of peak urinary flow rate and safety during a seven-day multiple-dosing period. Peak urinary flow rate was measured eight hours after the initial dose on days one and 15, and at eight hours after dosing on days four, eight, 18, and 21. Safety measurements included blood pressure, heart rate, reported adverse events, and abnormal laboratory values.

The results of 34 patients who completed the trial showed that eight hours after their initial dose, those treated with Uroxatral had an improved average peak flow rate of 3.2 mL/second. The drug's effect was confirmed following three days of continuous therapy. By contrast, patients given a placebo showed only a 1.1 mL/second change from baseline (p=0.002). No serious adverse events were reported, and overall, the incidence of adverse events was low (three patients treated with alfuzosin experienced dizziness, compared to one patient given placebo).

Important Safety Information

Uroxatral(R) should not be used in patients with moderate to severe hepatic insufficiency (Childs-Pugh categories B and C), since Uroxatral(R) blood levels are increased in these patients. Uroxatral(R) should not be used in combination with CYP3A4 inhibitors such as ketoconazole, itraconazole, and ritonavir. Caution should be used in patients with severe renal insufficiency (creatinine clearance <30 mL/min). Uroxatral(R) should not be used in combination with other alpha-blockers. If symptoms of angina pectoris should newly appear or worsen, the use of Uroxatral(R) should be discontinued. In a study of QT effect in 45 healthy males, the QT effect appeared less with Uroxatral(R) 10 mg than with 40 mg, and the effect of Uroxatral(R) 40 mg did not appear as large as that of the active control moxifloxacin at its therapeutic dose. This should be considered in clinical decisions to prescribe Uroxatral(R) for patients with a known history of QT prolongation or patients who are taking medications known to prolong QT. There has been no signal of Torsades de Pointe in the extensive post marketing experience with Uroxatral(R) worldwide. There are no known pharmacokinetic/pharmacodynamic studies of the effects of other alpha-blockers on cardiac repolarization. Carcinoma of the prostate and BPH cause many of the same symptoms. These two diseases frequently coexist. Therefore, patients thought to have BPH should be examined prior to starting therapy with Uroxatral(R) to rule out the presence of carcinoma of the prostate. Postural hypotension with or without symptoms may develop within a few hours following administration of Uroxatral(R). As with all alpha-blockers, there is a potential for syncope. Patients should be warned of the possible occurrence of such events and should avoid situations where injury could result should syncope occur. In clinical trials, the most common side effects occurring in >(or equal to) 2% of patients and more frequently than placebo were dizziness (5.7% versus 2.8%), upper respiratory tract infection (3.0% versus 0.6%), headache (3.0% versus 1.8%), and fatigue (2.7% versus 1.8%).

Uroxatral (generic name alfuzosin once-daily extended-release 10 mg tablets) is a prescription alpha(1)-blocker that provides effective relief of the signs and symptoms of BPH.(ii)

The ALFIRST trial was sponsored by Sanofi-Synthelabo. Uroxatral(R) is marketed in the United States by Sanofi-Synthelabo (Euronext: SAN / NYSE: SNY)

Urological Sciences Research Foundation is a non-profit organization founded in 1992 by its current medical director, Leonard S. Marks, M.D. The primary mission of the foundation is to help advance the understanding of common urologic problems, increase the range of effective treatments for such conditions, and inform the medical and lay public of these problems and treatments. Diseases of the prostate are the main focus for research projects of the Foundation. USRF is located in Culver City, CA. For more information log onto http://www.usrf.org/.

(i) Medina JJ, et al. Benign prostatic hyperplasia (the aging prostate). Med Clin North Am. 1999;83:1213-1229. From Sanofi-Synthelabo press release, November 3, 2003 (SS launches UROXATRAL in the United States... ) (ii) All references in this graph from BPH Product Profiles, prepared by ARK Consulting. December 16, 2002. From Sanofi-Synthelabo.

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CONTACT: Joe Landi of Landmark Communications, +1-201-585-9303,jlandi@prland.com

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