Abstract
Background
Guidelines for the management of hypertension recommend using drugs with different
mechanisms of action in antihypertensive regimens that include simple single-pill
fixed-dose combination (FDC) products.
Objective
The objective of this study was to compare the efficacy and tolerability of the FDC
of azilsartan (AZI) and amlodipine besylate (AML) with those of AZI monotherapy and
AML monotherapy in Japanese patients with grade 1 to 2 essential hypertension.
Methods
This was a multicenter, randomized, double-blind, parallel-group study. After receiving
placebo during a 4-week run-in period in a single-blind manner, patients were randomized
to receive 1 of the following 5 treatments for 8 weeks: FDC containing AZI 20 mg and
AML 5 mg (AZI/AML 20/5 mg), FDC containing AZI 20 mg and AML 2.5 mg (AZI/AML 20/2.5
mg), AZI 20 mg, AML 5 mg, or AML 2.5 mg once daily in a fasting or fed state. The
primary end point was the change from baseline (week 0) in the seated trough diastolic
blood pressure at week 8 (last observation carried forward [LOCF]), and the secondary
end point was the change from baseline in the seated trough systolic blood pressure
at week 8 (LOCF). Tolerability was assessed based on adverse events, vital signs,
and physical examination findings.
Results
Of the 800 patients who provided informed consent, 603 were randomized to receive
AZI/AML 20/5 mg (150 patients), AZI/AML 20/2.5 mg (151 patients), AZI 20 mg (151 patients),
AML 5 mg (75 patients), or AML 2.5 mg (76 patients). The mean baseline systolic/diastolic
blood pressure was 160.7/100.3 mm Hg. The mean change from baseline in seated blood
pressure at week 8 (LOCF) was −35.3/−22.3 mm Hg in the AZI/AML 20/5 mg group and −31.4/−19.2
mm Hg in the AZI/AML 20/2.5 mg group, indicating a reduction significantly greater
than that in corresponding monotherapy groups (−21.5/−13.9 mm Hg in the AZI 20 mg
group, −26.4/−15.5 mm Hg in the AML 5 mg group, and −19.3/−11.6 mm Hg in the AML 2.5
mg group; p < 0.0001 for all contrast tests). No remarkable difference was found in the incidences
of adverse events, vital signs, and physical examination findings among the treatment
groups.
Conclusion
This study found that the FDC of AZI/AML 20/5 mg and 20/2.5 mg exhibited greater antihypertensive
effects compared with each monotherapy. The FDC of AZI/AML had a similar safety profile
to that of each monotherapy and was tolerable to Japanese patients with grade 1 to
2 essential hypertension.
Japan Pharmaceutical Information Center registration
Japic CTI-111606.
Key words
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Article info
Publication history
Published online: April 14, 2014
Accepted:
March 14,
2014
Identification
Copyright
© 2014 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
