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 ch aracterizing the clinical utility of the controlled-release gastrointestina l therapeutic system (GITS) formulation of doxazosin in the treatment of be nign prostatic hyperplasia (BPH). Patients and methods Two pivotal randomized, double-blind studies of doxazo sin GITS for BPH were assessed by an integrated analysis. Both studies incl uded a 2-week washout period, a 2-week single-blind placebo run-in phase, a nd a 13-week double-blind treatment phase. One study compared doxazosin GIT S, doxazosin standard (-S) and placebo in 795 men; the other compared doxaz osin 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 w as initiated at 1 mg once daily and titrated to a maximum of 8 mg once dail y over 7 weeks as needed to achieve optimal symptom control. The primary ou tcome measures were mean changes from baseline to the final visit for the I nternational Prostate Symptom Score (IPSS) and maximum urinary flow rate (Q (max)) in the per-protocol population. Numerous symptom- and urinary-relate d secondary outcomes were assessed, as were effects of therapy on male erec tile dysfunction measured using the International Index of Erectile Functio n (IIEF) in one study. Results Both doxazosin GITS and doxazosin-S significantly improved the symp toms of BPH, as shown by a 45% reduction for each in total IPSS from baseli ne to final visit, compared with a 34% reduction in patients on placebo. Do xazosin GITS and doxazosin-S produced comparable improvements in Q(max) tha t were significantly greater than with placebo, with a greater improvement sooner after treatment with doxazosin GITS than with doxazosin-S. Nearly ha lf of the patients on doxazosin GITS had symptom relief at the 4-mg startin g dose. A similar number of patients in both doxazosin groups were titrated to the maximum dose. Secondary outcomes were consistent with the primary e ffects. Both doxazosin GITS and doxazosin-S produced significant improvemen ts in sexual function according to IIEF scores among those with dysfunction at baseline. The overall incidence of adverse events was similar among pat ients treated with doxazosin GITS and placebo, and slightly lower than thos e on doxazosin-S. There was no apparent difference in the type of adverse e vents 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 r educing the clinical symptoms of BPH and improving Q(max), and as effective as doxazosin-S. Both doxazosin formulations improved sexual function in pa tients with BPH and sexual dysfunction at baseline. Doxazosin GITS produced a therapeutic effect equivalent to that of doxazosin-S, but with fewer tit ration steps and a slightly lower overall incidence of adverse events.