Elsevier

Urology

Volume 63, Issue 4, April 2004, Pages 709-715
Urology

Adult urology
Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia

https://doi.org/10.1016/j.urology.2004.01.001Get rights and content

Abstract

Objectives

To assess the long-term safety and efficacy of dutasteride, a dual type 1 and type 2 5-α-reductase inhibitor, in the treatment of symptomatic benign prostatic hyperplasia and associated lower urinary tract symptoms.

Methods

Data from two Phase IIIa multicenter, randomized, placebo-controlled trials of 2-year duration plus a 2-year open-label extension were pooled and analyzed. The entry criteria included age 50 years old or older, clinical diagnosis of benign prostatic hyperplasia, prostate volume of 30 cm3 or greater, American Urological Association symptom score of 12 or greater, peak urinary flow rate of 15 mL/s or less, and prostate-specific antigen level of 1.5 ng/mL or greater but less than 10 ng/mL.

Results

A total of 2802 men were randomized into the double-blind phase of the two studies with 1908 patients (68%) completing the study. Of these, 1570 subjects were enrolled in the open-label phase, and 569 subjects received dutasteride for 48 months. Changes at the 48-month visit for dutasteride/dutasteride-treated subjects included improvement in prostate volume (−26.2%), American Urological Association Symptom Index (−6.1 points), and peak urinary flow rate (+2.8 mL/s). Changes for the placebo/dutasteride group included prostate volume (−20.7%), American Urological Association Symptom Index (−5.3 points), and peak urinary flow rate (+1.8 mL/s). Acute urinary retention and surgery occurred in a small percentage of subjects (less than 2% and less than 1%) in the open-label extension phase. Dutasteride was well tolerated with no statistically significant increase in drug-related adverse events during the open-label extension and no adverse laboratory trends.

Conclusions

Dual inhibition of 5-α-reductase with dutasteride provided sustained efficacy in subjects with symptomatic benign prostatic hyperplasia treated for 48 months. Near-complete, long-term suppression of dihydrotestosterone (93% at 48 months) with dutasteride did not lead to an increase in adverse events compared with that reported in the 2-year period.

Section snippets

Material and methods

At the time of writing, the data from the two U.S. studies, ARIA3001 and ARIA3002, were available. These were 2-year, double-blind, randomized, placebo-controlled trials with an additional 2-year open-label phase. During the open-label portion of the study, subjects initially receiving dutasteride continued to take dutasteride (dutasteride/dutasteride group), and those initially receiving placebo began to take open-label dutasteride (placebo/dutasteride group). The design of the double-blind

Patient demographics

A total of 2802 men were randomized into the double-blind phase of the two studies; 1908 (68%) completed the 2-year double-blind phase. In the open-label phase of the study, 1570 subjects were enrolled; 778 had previously received placebo and 792 had previously received dutasteride for the 2-year double-blind phase (Fig. 1). Overall, 569 subjects received dutasteride for 48 months. Table I includes the data for subjects in the double-blind and open-label ITT populations.

Changes in the

Comment

Inhibition of 5-α-reductase reduces symptoms of BPH and lowers the risk of long-term disease-related sequelae.4, 5, 6 Dutasteride, which inhibits both type 1 and type 2 isoenzymes of 5-α-reductase, reduces circulating DHT by more than 90% and has been shown to be safe and efficacious in three large-scale, 2-year Phase IIIa studies.4 Two of these studies, in which subjects completed an additional 24-month open-label phase, provide 4 years of data supporting the continued effectiveness and

Conclusions

Dual inhibition of the type 1 and type 2 5-α-reductase isoenzymes with dutasteride provided sustained and durable efficacy in symptomatic BPH subjects treated for 48 months, with clinically relevant improvements in prostate volume, AUA-SI, and Qmax. Symptom and flow rate improvements at 48 months in the dutasteride/dutasteride-treated patients were comparable to those seen with alpha-receptor blocking agents. The incidence of AUR and the need for BPH-related surgery was low. The low incidence

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This study was funded by GlaxoSmithKline.

C. G. Roehrborn is a study investigator funded by GlaxoSmithKline and Merck; L. S. Marks is a study investigator funded by GlaxoSmithKline, Merck, Sanofi Synthelabo, Beckman Coulter, and Lilly; T. Fenter, S. Freedman, and J. Tuttle are study investigators funded by GlaxoSmithKline; and M. Gittelman is a study investigator funded by GlaxoSmithKline, Merck, and Sanofi Synthelabo.

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