A combined analysis of double‐blind trials of the efficacy and tolerability of doxazosin‐gastrointestinal therapeutic system, doxazosin standard and placebo in patients with benign prostatic hyperplasia

Abstract

Objective To report an integrated analysis of two previous studies fully characterizing the clinical utility of the controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin in the treatment of benign prostatic hyperplasia (BPH). Patients and methods Two pivotal randomized, doubleblind studies of doxazosin GITS for BPH were assessed by an integrated analysis. Both studies included a 2-week washout period, a 2-week single-blind placebo run-in phase, and a 13-week double-blind treatment phase.One study compared doxazosin GITS, doxazosin standard (-S) and placebo in 795 men; the other compared doxazosin GITS and doxazosin-S in 680 men. Doxazosin GITS was initiated at 4 mg once daily and titrated to 8 mg once daily after 7 weeks, and doxazosin-S was initiated at 1 mg once daily and titrated to a maximum of 8 mg once daily over 7 weeks as needed to achieve optimal symptom control. The primary outcome measures were mean changes from baseline to the ®nal visit for the International Prostate Symptom Score (IPSS) and maximum urinary¯ow rate (Q max ) in the per-protocol population. Numerous symptom-and urinary-related secondary outcomes were assessed, as were effects of therapy on male erectile dysfunction measured using the International Index of Erectile Function (IIEF) in one study. Results Both doxazosin GITS and doxazosin-S signi®-cantly improved the symptoms of BPH, as shown by a 45% reduction for each in total IPSS from baseline to ®nal visit, compared with a 34% reduction in patients on placebo. Doxazosin GITS and doxazosin-S produced comparable improvements in Q max that were signi®-cantly greater than with placebo, with a greater improvement sooner after treatment with doxazosin GITS than with doxazosin-S. Nearly half of the patients on doxazosin GITS had symptom relief at the 4-mg starting dose. A similar number of patients in both doxazosin groups were titrated to the maximum dose. Secondary outcomes were consistent with the primary effects. Both doxazosin GITS and doxazosin-S produced signi®cant improvements in sexual function according to IIEF scores among those with dysfunction at baseline. The overall incidence of adverse events was similar among patients treated with doxazosin GITS and placebo, and slightly lower than those on doxazosin-S. There was no apparent difference in the type of adverse events reported for the two formulations of doxazosin, although most adverse events were reported at a lower frequency with doxazosin GITS. Conclusion Doxazosin GITS is signi®cantly more effective than placebo in reducing the clinical symptoms of BPH and improving Q max , and as effective as doxazosin-S. Both doxazosin formulations improved sexual function in patients with BPH and sexual dysfunction at baseline. Doxazosin GITS produced a therapeutic effect equivalent to that of doxazosin-S, but with fewer titration steps and a slightly lower overall incidence of adverse events.

The effect of α-blocker therapy on erectile functions in patients with lower urinary tract symptoms due to benign prostate hyperplasia

“…The QoL had decreased by 1.0 point compared with the baseline in patients with ED, whereas in non-ED group, it decreased by 1.9 points. This result was consistent with previous studies findings of significant reductions in total IPSS and QoL, and substantial increases in npg Q max with doxazosin [7,8]. In both studies, the α1-adrenoceptor antagonists improved symptom scores by 35%-40% vs. baseline and Q max by 16%-26% vs. baseline for 3 months of treatment.…”

“…As shown in our study, doxazosin produced significant improvements at the sixth week of treatment. Our results are similar to Kirby et al [7] who reported an analysis of doubleblind trials of the efficacy and tolerability of doxazosin. In that study, although the differences between the mean changes of IPSS and Q max in doxazosin groups and placebo were significant, the mean change in placebo group over baseline was also significant.…”

“…The selective α1-adrenoceptor antagonist doxazosin mesylate is effective and well tolerated in the treatment of BPH, producing marked symptomatic relief and significant improvement in urinary flow rates [6]. On the basis of the results of combined analysis of two studies conducted by Kirby et al [7], doxazosin improves sexual functions in BPH patients with sexual dysfunction at baseline. In this study, we aimed to compare the effects of doxazosin improving LUTS and erectile functions in BPH patients with and without ED at baseline.…”

Clinical ease of using doxazosin in BPH patients with and without hypertension

“…In trials of doxazosin GITS and doxazosin standard in patients with BPH, 21,22 both formulations were shown to significantly improve the symptoms of BPH, as shown by a 45% reduction for each in total IPSS from baseline to final visit, compared with a 34% reduction in patients taking placebo. Doxazosin GITS and doxazosin standard produced comparable improvements in Q max that were significantly greater than with placebo, with a greater improvement sooner after treatment with doxazosin GITS than with doxazosin standard.…”

“…Doxazosin GITS is as effective as standard doxazosin in the treatment of hypertension [16][17][18][19][20] or BPH. 18,[21][22][23] Although the blood pressure-lowering effect of doxazosin is a therapeutic advantage in patients with comorbid BPH and hypertension, it has been erroneously perceived as less desirable in normotensive men. However, the degree of blood pressure lowering with doxazosin differs markedly in hypertensive and normotensive patients.…”