The Impact of Azilsartan Medoxomil Treatment (Capsule Formulation) at Doses Ranging From 10 to 80 mg: Significant, Rapid Reductions in Clinic Diastolic and Systolic Blood Pressure

Abstract

In this phase 2, multicenter, parallel-group, double-blind, dose-ranging study, hypertensive adults (n=449) were randomized to receive one of five doses of a capsule formulation of azilsartan medoxomil (AZL-M; 5, 10, 20, 40, 80 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. AZL-M provided rapid statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) vs placebo at all doses except 5 mg. Placebo-subtracted changes were greatest with the 40 mg dose (DBP, -5.7 mm Hg; SBP, -12.3 mm Hg). Clinic changes with AZL-M (all doses) were statistically indistinguishable vs OLM, although there were greater reductions with AZL-M 40 mg using 24-hour ambulatory blood pressure. Adverse event frequency was similar in the AZL-M and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL-M tablet in the dose range of 20 to 80 mg/d.

Figure 1

Changes from baseline in sitting clinic diastolic blood pressure over 8 weeks. The top panel shows least squares (LS) mean change±standard error (SE) at 8 weeks (last observation carried forward). The bottom panel shows LS mean change±SE over 8 weeks (observed cases). AZL‐M indicates azilsartan medoxomil; OLM, olmesartan medoxomil. *P<.05 vs placebo. ***P<.001 vs placebo.

Figure 2

Changes from baseline in sitting clinic systolic blood pressure over 8 weeks. The top panel shows least squares (LS) mean change±standard error (SE) at 8 weeks (last observation carried forward). The bottom panel shows LS mean change±SE over 8 weeks (observed cases). AZL‐M indicates azilsartan medoxomil; OLM, olmesartan medoxomil. *P<.05 vs placebo. ***P<.001 vs placebo.

Figure 3

Mean 0 to 24‐hour ambulatory blood pressure monitoring (ABPM) measurements: change from baseline to final visit for diastolic blood pressures (top) and systolic blood pressure (bottom). LS indicates least squares; AZL‐M, azilsartan medoxomil. ***P<.001 vs placebo. ^† P<.05 vs olmesartan medoxomil (OLM).