PMID- 25850881
OWN - NLM
STAT- MEDLINE
DCOM- 20160627
LR  - 20190221
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 37
IP  - 11
DP  - 2015 Nov 1
TI  - A Randomized, Multicenter, Double-blind, Placebo-controlled, 3 x 3 Factorial 
      Design, Phase II Study to Evaluate the Efficacy and Safety of the Combination of 
      Fimasartan/Amlodipine in Patients With Essential Hypertension.
PG  - 2581-2596.e3
LID - S0149-2918(15)00089-2 [pii]
LID - 10.1016/j.clinthera.2015.02.019 [doi]
AB  - 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 x 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 (c) 2015 Elsevier HS Journals, Inc. All rights reserved.
FAU - Lee, Hae-Young
AU  - Lee HY
AD  - Seoul National University Hospital, Seoul, Republic of Korea.
FAU - Kim, Yong-Jin
AU  - Kim YJ
AD  - Seoul National University Hospital, Seoul, Republic of Korea.
FAU - Ahn, Taehoon
AU  - Ahn T
AD  - Gachon University Gil Medical Center, Incheon, Republic of Korea.
FAU - Youn, Ho-Joong
AU  - Youn HJ
AD  - Catholic University of Korea, Seoul St. Mary׳s Hospital, Seoul, Republic of 
      Korea.
FAU - Chull Chae, Shung
AU  - Chull Chae S
AD  - Kyungpook National University Hospital, Daegu, Republic of Korea.
FAU - Seog Seo, Hong
AU  - Seog Seo H
AD  - Korea University Guro Hospital, Seoul, Republic of Korea.
FAU - Kim, Ki-Sik
AU  - Kim KS
AD  - Daegu Catholic University Medical Center, Daegu, Republic of Korea.
FAU - Rhee, Moo-Yong
AU  - Rhee MY
AD  - Dongguk University Ilsan Hospital, Ilsan, Republic of Korea.
FAU - Choi, Dong-Ju
AU  - Choi DJ
AD  - Seoul National University Bundang Hospital, Sungnam, Busan, Republic of Korea.
FAU - Kim, Jae-Joong
AU  - Kim JJ
AD  - Asan Medical Center, Seoul, Republic of Korea.
FAU - Chun, Kook-Jin
AU  - Chun KJ
AD  - Pusan University Yangsan Hospital, Busan, Republic of Korea.
FAU - Yoo, Byung-Su
AU  - Yoo BS
AD  - Wonju Christian Hospital, Wonju, Republic of Korea.
FAU - Park, Jong-Seon
AU  - Park JS
AD  - Yeungnam University Medical Center, Daegu, Republic of Korea.
FAU - Oh, Seok-Kyu
AU  - Oh SK
AD  - Wonkwang University School of Medicine and Hospital, Iksan, Republic of Korea.
FAU - Kim, Dong-Soo
AU  - Kim DS
AD  - Inje University Busan Paik Hospital, Busan, Republic of Korea.
FAU - Kwan, Jun
AU  - Kwan J
AD  - Inha University Hospital, Incheon, Republic of Korea.
FAU - Ahn, Youngkeun
AU  - Ahn Y
AD  - Chonnam National University Hospital, Gwangju, Republic of Korea.
FAU - Bae Park, Jeong
AU  - Bae Park J
AD  - Cheil General Hospital, Seoul, Republic of Korea.
FAU - Jeong, Jin-Ok
AU  - Jeong JO
AD  - Chungnam National University Hospital, Daegu, Republic of Korea.
FAU - Hyon, Min-Soo
AU  - Hyon MS
AD  - Soonchunhyang University Hospital, Seoul, Republic of Korea.
FAU - Cho, Eun-Joo
AU  - Cho EJ
AD  - Catholic University of Korea, St. Paul׳s Hospital, Seoul, Republic of Korea.
FAU - Han, Kyoo-Rok
AU  - Han KR
AD  - Kangdong Sacred Heart Hospital, Seoul, Republic of Korea.
FAU - Kim, Doo-Il
AU  - Kim DI
AD  - Inje University Haeundae Paik Hospital, Busan, Republic of Korea.
FAU - Joo, Seung-Jae
AU  - Joo SJ
AD  - Jeju University Hospital, Jeju, Republic of Korea.
FAU - Shin, Jin-Ho
AU  - Shin JH
AD  - Hanyang University Hospital, Seoul, Republic of Korea.
FAU - Sung, Ki-Chul
AU  - Sung KC
AD  - Kangbuk Samsung Hospital, Seoul, Republic of Korea.
FAU - Jeon, Eun-Seok
AU  - Jeon ES
AD  - Samsung Medical Center, Seoul, Republic of Korea. Electronic address: 
      eunseok.jeon@samsung.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT01518998
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150404
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Pyrimidines)
RN  - 0 (Tetrazoles)
RN  - 1J444QC288 (Amlodipine)
RN  - P58222188P (fimasartan)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Amlodipine/*administration & dosage
MH  - Antihypertensive Agents/*administration & dosage
MH  - Biphenyl Compounds/*administration & dosage
MH  - Blood Pressure/drug effects
MH  - Double-Blind Method
MH  - Essential Hypertension
MH  - Female
MH  - Headache/chemically induced
MH  - Humans
MH  - Hypertension/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Pyrimidines/*administration & dosage
MH  - Tetrazoles/*administration & dosage
OTO - NOTNLM
OT  - amlodipine
OT  - angiotensin receptor blocker
OT  - calcium channel blocker
OT  - fimasartan
OT  - hypertension
EDAT- 2015/04/09 06:00
MHDA- 2016/06/28 06:00
CRDT- 2015/04/09 06:00
PHST- 2014/11/07 00:00 [received]
PHST- 2015/01/16 00:00 [revised]
PHST- 2015/02/04 00:00 [accepted]
PHST- 2015/04/09 06:00 [entrez]
PHST- 2015/04/09 06:00 [pubmed]
PHST- 2016/06/28 06:00 [medline]
AID - S0149-2918(15)00089-2 [pii]
AID - 10.1016/j.clinthera.2015.02.019 [doi]
PST - ppublish
SO  - Clin Ther. 2015 Nov 1;37(11):2581-2596.e3. doi: 10.1016/j.clinthera.2015.02.019. 
      Epub 2015 Apr 4.