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Positive Results Support Long-Term Efficacy and Tolerability of Dutasteride

CHICAGO, April 29 /PRNewswire-FirstCall/ -- The latest results from clinical studies on Avodart™ (dutasteride) -- presented today at the American Urological Association (AUA) Annual Meeting -- showed that out to four years of therapy, men taking the drug for symptomatic benign prostatic hyperplasia (BPH, also known as enlarged prostate) had a sustained improvement in urinary symptoms, urinary flow rates and prostate volume reduction. Additionally, long-term treatment resulted in a low incidence of drug-related side effects. The incidence of most drug-related side effects decreased with duration of treatment.

"Physicians now have additional evidence supporting long-term use of Avodart in men with BPH," said Claus Roehrborn, MD, the principal trial investigator, professor and chairman of the Department of Urology at the University of Texas Southwestern Medical Center, Dallas. "Previous data showed the efficacy and tolerability of Avodart at two years. Now, we have additional data confirming that patients treated with Avodart for four years experience enduring symptom improvement and are able to tolerate the drug long term."

The new data presented today at AUA were from two-year open-label extensions of the Phase III clinical trials for Avodart. In its Phase III trials, Avodart 0.5 mg/day (n=2,167) or placebo (n=2,158) was evaluated in male subjects with BPH in three two-year multicenter, placebo-controlled, double-blind studies, each with two-year open-label extensions. Patients in either arm (placebo or Avodart) of the Phase III trials were eligible to receive open-label Avodart after completing the two-year double-blind phase.

Two of these trials were conducted entirely in the U.S. and have been completed. The third trial is ongoing. Of the 2,802 patients originally enrolled in the two U.S. trials, 1,908 patients completed the double-blind, placebo-controlled phase. One thousand five hundred seventy of these patients entered the open label phase.

Seven hundred ninety-two patients from these two trials were treated with Avodart during both the double-blind and open-label phases. Seven hundred seventy-eight patients from these two trials were on placebo during the double-blind phase, then switched to Avodart for the open-label phase.

Selection criteria for the double-blind phase of the Avodart Phase III trials included men aged 50 and above with a serum PSA level between 1.5 and 10 ng/mL, BPH diagnosed by medical history and physician examination, including enlarged prostate (greater than or equal to 30 cc) by transrectal ultrasound, and BPH symptoms that were moderate to severe according to the American Urological Association Symptom Index (AUA-SI) score.

Patients on Avodart (dutasteride years 0-2 and dutasteride years 2-4) experienced the following improvements at four years compared to baseline:

* 6.1 point AUA-SI score improvement * 26.2 percent prostate volume reduction * 2.8mL/sec improvement in maximum urinary flow

Additionally, long-term treatment resulted in a low incidence of drug-related side effects. This incidence decreased with duration of treatment. The incidence of the most frequently observed drug-related side effects during the open-label phase (years 3-4) were: gynecomastia (1.9 percent for year 3; 1 percent for year 4); impotence (1.6 percent for year 3; 0.4 percent for year 4); decreased libido (0.5 percent for year 3; 0 percent for year 4); and ejaculation disorders (0.3 percent for year 3; 0.1 percent for year 4).

"Patients who received Avodart for four years had sustained improvements in symptoms, urinary flow and prostate volume reduction, with a declining incidence of drug-related side effects," said Dr. Roehrborn. "This supports the long-term efficacy and tolerability of Avodart for men with symptomatic BPH and enlarged prostates."

Background: Two-year Double-blind Phase III Trials

Avodart is the first and only medicine that inhibits both the type 1 and type 2 enzymes responsible for the conversion of testosterone into dihydrotestosterone (DHT) in the prostate and other tissues. In the two-year double-blind phase of its Phase III trials, Avodart decreased levels of DHT by 90 percent after two weeks and by 93 percent at two years. By reducing DHT levels, Avodart reduces the size of an enlarged prostate. In clinical studies, this reduction in prostate volume began as early as one month and continued through the treatment period.

In the two-year double-blind phase of the trials, Avodart was shown to improve urinary symptoms and reduce the risk of acute urinary retention (AUR, the sudden, complete inability to urinate) and the need for BPH-related surgery.

Clinical trials of Avodart showed the medication was generally well-tolerated. Incidence of most drug-related sexual side effects decreased over the course of the study. Incidence of drug-related breast tenderness and breast enlargement remained constant over the treatment period, but was reported in only a small percentage of men. Ejaculate volume may be decreased in some patients with continued treatment. This decrease did not appear to interfere with normal sexual function in healthy volunteers.

Avodart should not be used in women and children. Women who are pregnant or may become pregnant should not handle Avodart directly because of the possibility of absorption of Avodart and the subsequent potential risk to a male fetus.

Lower urinary tract symptoms of BPH can be indicative of other urological diseases, including prostate cancer. Patients should be assessed to rule out other urological diseases prior to treatment with Avodart. Patients with a large residual urinary volume and/or severely diminished urinary flow may not be good candidates for 5 alpha-reductase inhibitor therapy and should be carefully monitored for obstructive uropathy.

Men treated with Avodart should not donate blood until at least six months after their final dose to prevent giving Avodart to a pregnant woman through a blood transfusion. Men with an allergic reaction to Avodart or its ingredients should not take the medication. Men with liver disease should talk to their doctor before taking Avodart.

Avodart will reduce the amount of PSA measured in the blood, but it does this in a predictable manner. A physician should be aware of this effect and can continue to use the PSA test to screen patients for prostate cancer.

While some men have fewer problems and symptoms after three months of treatment, a treatment period of at least six months is usually necessary to see if Avodart will improve symptoms.

Avodart received approval by the U.S. Food and Drug Administration (FDA) for the two-year double-blind, placebo-controlled data in October 2002, as well as European Marketing Authorization from the European Agency for the Evaluation of Medicinal Products (EMEA) in December 2002. Avodart became available by prescription in the U.S. in December 2002.

GlaxoSmithKline, with U.S. operations in Philadelphia and Research Triangle Park, N.C., is one of the world's leading research-based pharmaceutical and health care companies. GlaxoSmithKline is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

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