title: Evaluation of the efficacy and tolerability of fixed-dose combination therapy of azilsartan and amlodipine besylate in Japanese patients with grade I to II essential hypertension.
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.
  
  
  CONCLUSIONS
  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.
  Japic CTI-111606.
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address: rakugi@geriat.med.osaka-u.ac.jp.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.affiliation: Pharmaceutical Development Division, Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Nakata
authors.affiliation: Pharmaceutical Development Division, Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors.forename: Emma
authors.initials: E
authors.lastname: Sasaki
authors.affiliation: Pharmaceutical Development Division, Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kagawa
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D044466:Asian People; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D000075222:Essential Hypertension; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010069:Oxadiazoles / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D010069:Oxadiazoles; D017311:Amlodipine; C521273:azilsartan
keywords: amlodipine besylate; azilsartan; essential hypertension; fixed-dose combination