Abstract
Purpose
The objective of this study was to evaluate the efficacy and safety of a fimasartan/amlodipine
combination in patients with hypertension and to determine the optimal composition
for a future single-pill combination formulation.
Methods
This Phase II study was conducted by using a randomized, multicenter, double-blind,
placebo-controlled, 3 × 3 factorial design. After a 2-week placebo run-in period,
eligible hypertensive patients (with a sitting diastolic blood pressure [SiDBP] between
90 and 114 mm Hg) were randomized to treatment. They received single or combined administration
of fimasartan at 3 doses (0, 30, and 60 mg) and amlodipine at 3 doses (0, 5, and 10
mg) for 8 weeks. The primary efficacy end point was the change in SiDBP from baseline
and at week 8; secondary end points included the change in SiDBP from baseline and
at week 4 and the changes in sitting systolic blood pressure from baseline and at
weeks 4 and 8. Treatment-emergent adverse events (AEs) were also assessed.
Findings
420 Korean patients with mild to moderate hypertension were randomly allocated to
the 9 groups. Mean (SD) SiDBP changes in each group after 8 weeks were as follows:
placebo, –6.0 (8.5) mm Hg; amlodipine 5 mg, –10.6 (9.2) mm Hg; amlodipine 10 mg, –15.9
(7.2) mm Hg; fimasartan 30 mg, –10.1 (9.1) mm Hg; fimasartan 60 mg, –13.0 (10.0) mm
Hg; fimasartan 30 mg/amlodipine 5 mg, –16.2 (8.5) mm Hg; fimasartan 30 mg/amlodipine
10 mg, –19.5 (7.5) mm Hg; fimasartan 60 mg/amlodipine 5 mg, –16.6 (6.9) mm Hg; and
fimasartan 60 mg/amlodipine 10 mg, –21.5 (8.3) mm Hg. All treatment groups produced
significantly greater reductions in blood pressure compared with the placebo group.
In addition, all combination treatment groups had superior reductions in blood pressure
compared with the monotherapy groups. In the combination treatment groups, doubling
fimasartan dose in the given dose of amlodipine did not show further BP reduction,
whereas doubling amlodipine dose showed significantly further BP reduction in the
given dose of fimasartan. During the study period, 75 (17.9%) of 419 patients experienced
110 AEs. Ninety-five AEs were mild, 9 were moderate, and 6 were severe in intensity.
Eight patients discontinued the study due to AEs. There was no significant difference
in incidence of AEs among groups (P = 0.0884). The most common AE was headache (12 patients [2.9%]), followed by dizziness
(11 patients [2.6%]) and elevated blood creatine phosphokinase levels (6 patients
[1.4%]).
Implications
Fimasartan combined with amlodipine produced superior blood pressure reductions and
low levels of AEs compared with either monotherapy. Therefore, a single-pill combination
with fimasartan 60 mg/amlodipine 10 mg will be developed. ClinicalTrials.gov: NCT01518998.
Key words
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Article info
Publication history
Published online: April 04, 2015
Accepted:
February 4,
2015
Identification
Copyright
© 2015 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
