Comparison of doxazosin GITS and standard doxazosin in the treatment of high blood pressure.
OBJECTIVE
To examine (1) the relative therapeutic equivalence of 4 mg doxazosin gastrointestinal therapeutic system (DOX GITS) and 4 mg doxazosin standard (DOX-S4) and (2) the efficacy and safety of 4 mg DOX GITS versus 2 mg doxazosin standard (DOX-S2).


METHODS
Male or female patients aged 18-80 diagnosed with mild-to-moderate essential hypertension (sitting diastolic blood pressure (DBP) 95-110 mmHg and systolic blood pressure (SBP) < 180 mmHg) were randomized into the study.


METHODS
This double-blind, parallel, 9-week trial compared DOX-GITS with doxazosin standard (DOX-S) in 310 hypertensive patients. Following a 2-week placebo run-in phase, patients were randomized to receive DOX-GITS at 4 mg/d or DOX-S at 2 or 4 mg/d. DOX GITS dosage remained unchanged at 4 mg throughout the study. Titration in the DOX-S groups was initiated at Week 0 with 1 mg DOX-S and increased to 2 mg DOX-S at Week 1. Dosage in the DOX-S4 group was increased to 4 mg DOX-S at Week 3. Therapeutic equivalence was measured by the change from baseline in sitting diastolic BP (DBP). Efficacy was assessed using the change from baseline for all blood pressure measures. Safety analysis included evaluation of laboratory tests at clinic visits and adverse events (AEs).


RESULTS
Therapeutic equivalences between DOX GITS and DOX-S4 and DOX-S2 were established at all study visits except for a significant difference in favor of DOX GITS at Week 1 (p = 0.019) when the dose of DOX-S was 1 mg. All groups had a significant decrease in BP at all study visits compared with baseline. The proportion of patients who reached goal sitting DBP (< 90 mmHg) was similar among the three treatment groups, except at Week 1, when more patients in the DOX GITS group had obtained the goal compared with those in the DOX-S2 group (40.6% vs. 22.3%; p = 0.005). The proportion of patients who reached sitting SBP (< 140 mmHg) goal was similar among groups. AE profiles among the groups were similar.


CONCLUSIONS
DOX GITS was as effective as DOX-S in patients with mild-to-moderate hypertension. The improved pharmacokinetic profile of the GITS formulation compared with the standard formulation allows a therapeutic dose to be delivered earlier and without dose titration. Both formulations of doxazosin were well tolerated.
Department of Nephrology, Ulleval University Hospital, Oslo, Norway. ingrid.os@medisin.uio.no
I
I
Os
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017292:Doxazosin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004337:Drug Carriers; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013678:Technology, Pharmaceutical / Q000379:methods; D013810:Therapeutic Equivalency
D000924:Anticholesteremic Agents; D004337:Drug Carriers; D017292:Doxazosin