Lee, Hae-Young; Kim, Yong-Jin; Ahn, Taehoon; Youn, Ho-Joong; Chull Chae, Shung; Seog Seo, Hong; Kim, Ki-Sik; Rhee, Moo-Yong; Choi, Dong-Ju; Kim, Jae-Joong; Chun, Kook-Jin; Yoo, Byung-Su; Park, Jong-Seon; Oh, Seok-Kyu; Kim, Dong-Soo; Kwan, Jun; Ahn, Youngkeun; Bae Park, Jeong; Jeong, Jin-Ok; Hyon, Min-Soo; Cho, Eun-Joo; Han, Kyoo-Rok; Kim, Doo-Il; Joo, Seung-Jae; Shin, Jin-Ho; Sung, Ki-Chul; Jeon, Eun-Seok
Clinical therapeutics
2015Nov ; 37 ( 11 ) :2581-2596.e3.
PMID : 25850881
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Lee, Hae-Young - Seoul National University Hospital, Seoul, Republic of Korea.
Kim, Yong-Jin - Seoul National University Hospital, Seoul, Republic of Korea.
Ahn, Taehoon - Gachon University Gil Medical Center, Incheon, Republic of Korea.
Youn, Ho-Joong - Catholic University of Korea, Seoul St. Marys Hospital, Seoul, Republic of Korea.
Chull Chae, Shung - Kyungpook National University Hospital, Daegu, Republic of Korea.
Seog Seo, Hong - Korea University Guro Hospital, Seoul, Republic of Korea.
Kim, Ki-Sik - Daegu Catholic University Medical Center, Daegu, Republic of Korea.
Rhee, Moo-Yong - Dongguk University Ilsan Hospital, Ilsan, Republic of Korea.
Choi, Dong-Ju - Seoul National University Bundang Hospital, Sungnam, Busan, Republic of Korea.
Kim, Jae-Joong - Asan Medical Center, Seoul, Republic of Korea.
Chun, Kook-Jin - Pusan University Yangsan Hospital, Busan, Republic of Korea.
Yoo, Byung-Su - Wonju Christian Hospital, Wonju, Republic of Korea.
Park, Jong-Seon - Yeungnam University Medical Center, Daegu, Republic of Korea.
Oh, Seok-Kyu - Wonkwang University School of Medicine and Hospital, Iksan, Republic of Korea.
Kim, Dong-Soo - Inje University Busan Paik Hospital, Busan, Republic of Korea.
Kwan, Jun - Inha University Hospital, Incheon, Republic of Korea.
Ahn, Youngkeun - Chonnam National University Hospital, Gwangju, Republic of Korea.
Bae Park, Jeong - Cheil General Hospital, Seoul, Republic of Korea.
Jeong, Jin-Ok - Chungnam National University Hospital, Daegu, Republic of Korea.
Hyon, Min-Soo - Soonchunhyang University Hospital, Seoul, Republic of Korea.
Cho, Eun-Joo - Catholic University of Korea, St. Pauls Hospital, Seoul, Republic of Korea.
Han, Kyoo-Rok - Kangdong Sacred Heart Hospital, Seoul, Republic of Korea.
Kim, Doo-Il - Inje University Haeundae Paik Hospital, Busan, Republic of Korea.
Joo, Seung-Jae - Jeju University Hospital, Jeju, Republic of Korea.
Shin, Jin-Ho - Hanyang University Hospital, Seoul, Republic of Korea.
Sung, Ki-Chul - Kangbuk Samsung Hospital, Seoul, Republic of Korea.
Jeon, Eun-Seok - Samsung Medical Center, Seoul, Republic of Korea. Electronic address eunseok.jeon@samsung.com.
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. CI - Copyright ??2015 Elsevier HS Journals, Inc. All rights reserved.
keyword
amlodipine; angiotensin receptor blocker; calcium channel blocker; fimasartan; hypertension
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