Sanofi Press Release

Sanofi says drug in pharmacies November'03

New York City, November 24, 2003 -- Men with enlarged prostates who took the drug alfuzosin OD (Uroxatral® 10 mg once-daily) had nearly triple the improvement in urine flow of men taking a placebo, according to results of a multi-center study led by researchers at Urological Sciences Research Foundation in Culver City, California. Moreover, the improvement began within eight hours of first dose. The study, which appears in the November 2003 issue of Urology, also showed that alfuzosin’s effects were confirmed following three days of continuous therapy, and that the drug was safe and well tolerated.

According to Leonard S. Marks, M.D., medical director of Urological Sciences Research Foundation and lead author of the paper, the study is important because little was known about the efficacy of Uroxatral® and similar drugs (called alpha1-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.

“Alpha1-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® OD in men within hours of the first administration,” Dr. Marks said. “Our findings showed that the drug significantly increased urine flow as early as eight hours after the initial dose, and the incidence of side effects was low. We believe Uroxatral® OD has the potential to offer early benefits to men seeking relief from bothersome BPH symptoms.”

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. 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® 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 alpha1-blockers and a subsequent recurrence of urinary symptoms following treatment cessation. Patients were randomly assigned to receive either Uroxatral® 10 mg OD 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 alfuzosin had an improved average peak flow rate of 3.2 mL/second (at day 1 and 15). The drug’s effect was confirmed following three days of continuous therapy. By contrast, patients given a placebo showed only a 1.1mL/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).

VIDEO LINK:

Video of "Prostate muscle relaxation" (Alpha Blockade Mechanism)