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.

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, double-blind 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 final visit for the International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Qmax) 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 significantly improved 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 on placebo. Doxazosin GITS and doxazosin-S produced comparable improvements in Qmax that were significantly 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 significant 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 significantly more effective than placebo in reducing the clinical symptoms of BPH and improving Qmax, 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.

[Doxazosin in the gastrointestinal therapeutic system (GITS) and doxazosin standard in patients with benign prostatic hyperplasia. Double-blind trial of efficacy and tolerability]. / Doxazosin GITS und herkömmliches Doxazosin zur Behandlungder benignen Prostatahyperplasie. Doppelblindstudie zur Wirksamkeit und Verträglichkeit.

BACKGROUND AND METHOD: This randomized, doubleblind, multicenter, parallel-group, placebo-baseline study compared the effects of doxazosin GITS 4 mg or 8 mg once daily with doxazosin standard 1 mg to 8 mg once daily in 678 men with benign prostatic hyperplasia (BPH). Following a 2-week washout period and a 2-week, single-blind, placebo run-in phase, patients were randomized to 13 weeks of double-blind treatment with doxazosin GITS, initiated at 4 mg once daily and titrated to 8 mg once daily after 7 weeks, if needed, and doxazosin standard, initiated at 1 mg once daily, titrated to 2 mg after 1 week, to 4 mg at 3 weeks, and to 8 mg at 7 weeks if needed. The primary outcome measures were mean changes from baseline to the final visit for International Prostate Symptom Score (I-PSS) and maximum urinary flow rate in the per-protocol analysis (PPA) population. Secondary outcomes included other aspects of BPH symptoms and urinary flow; and assessment of sexual function in the PPA and intent-to-treat populations, as measured by the International Index of Erectile Function (IIEF). RESULTS: Doxazosin GITS and doxazosin standard produced clinically and statistically significant equivalent reductions in BPH symptoms, including least-square mean decreases in total I-PSS of -8.1 +/- 0.3 and -7.9 +/- 0.3 from baseline, respectively (p < 0.001 vs baseline for each). Both therapies significantly improved maximum urinary flow rates by 2.7 +/- 0.3 ml/s (least-squares mean change from baseline, p < 0.001). The beneficial effects of both therapies on secondary parameters of symptoms and urinary flow were consistent with these findings. Significant improvements in sexual function were observed with both therapies among individuals with sexual dysfunction at baseline. Nearly half of patients on doxazosin GITS achieved BPH symptom relief at the initial 4-mg dose.A similar number of patients in both doxazosin groups were titrated to the maximum dose of 8 mg for both formulations. While both agents were well tolerated, the incidence of at least one treatment-emergent adverse event was significantly lower among patients treated with doxazosin GITS (p = 0.003). CONCLUSIONS: Doxazosin GITS and doxazosin standard produced comparable significant reductions in BPH symptoms and improvements in maximum urinary flow rates. A therapeutic effect equivalent to that of doxazosin standard was achieved with doxazosin GITS with fewer titration steps and enhanced tolerability. Both formulations of doxazosin improved sexual function in individuals with dysfunction at baseline.