Efficacy and Tolerability of Fimasartan, a New Angiotensin Receptor Blocker, Compared With Losartan (50/100 mg): A 12-Week, Phase III, Multicenter, Prospective, Randomized, Double-Blind, Parallel-Group, Dose Escalation Clinical Trial With an Optional 12-Week Extension Phase in Adult Korean Patients With Mild-to-Moderate Hypertension

BackgroundAngiotensin receptor blockers (ARBs) is an effective and well tolerated first-line antihypertensive drug. Fimasartan is a newly developed ARB that has not been compared with other ARBs with regard to its efficacy and tolerability.ObjectiveThe goal of this study was to determine the noninferiority of fimasartan to losartan with regard to its efficacy and tolerability in adult Korean patients with mild-to-moderate hypertension.MethodsThis was a randomized, multicenter, double-blind, parallel group, dose escalation, Phase III, noninferiority clinical trial. Patients aged 18 to 70 years with mild-to-moderate hypertension were randomized to receive either fimasartan 60/120 mg daily or losartan 50/100 mg daily with optional titration. Antihypertensive efficacy and tolerability were evaluated for 12 weeks. The primary end point was noninferiority of improvement in mean siDBP from baseline to week 12 for fimasartan compared with losartan. The incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs) were evaluated to assess their tolerability. In addition, some patients whose blood pressure reached goal levels participated in a 24-week extension study for additional assessment of tolerability and efficacy.ResultsFive hundred six patients were randomly allocated to receive fimasartan (n = 256) or losartan (n = 250). There was no significant difference in baseline demographic characteristics between the 2 treatment groups (fimasartan-treated group—mean age, 53.96 [8.79] years; mean weight, 70.58 [11.73] kg; male, 68.02%; losartan-treated group—mean age, 53.58 [9.61] years; mean weight, 69.80 [11.08] kg; male, 70.17%). At week 12, siDBP was significantly decreased from baseline in both groups (−11.26 [7.53] mm Hg in the fimasartan group and −8.56 [7.72] mm Hg in the losartan group [P < 0.0001]). The between-group difference was 2.70 mm Hg (P = 0.0002), and the lower limit of the 2-sided 95% CI (1.27 mm Hg) was higher than the prespecified noninferiority margin (−2.5 mm Hg). The incidence of ADRs were 7.84% and 10.40% in the fimasartan and losartan groups, respectively (χ2 test, P = 0.3181). The efficacy of fimasartan was maintained over 24 weeks, and its tolerability was comparable with losartan in the extension study.ConclusionsIn this study with eligible adult Korean patients who had mild-to-moderate hypertension, the reduction of siDBP after 12 weeks of treatment with fimasartan 60/120 mg was noninferior to that of losartan 50/100 mg. By post hoc comparison, between-group differences in siDBP were significant in favor of fimasartan, suggesting superiority to losartan. There was no statistically significant difference in tolerability between the groups. This efficacy and tolerability were maintained throughout the additional 12-week extension study. ClinicalTrials.gov identifier: NCT00922480.This research was financially supported by Boryung Pharmaceutical Co. Ltd., Seoul, Republic of Korea. The sponsor supported the charge for medicine, laboratory test, and clinical research coordinator expenses. The study was initiated by Boryung Pharmaceutical and was designed, conducted, interpreted, and written by authors under the supervision of Dr. Oh. An external monitoring group (LSK Global PS) was involved in the collection and analysis of data. Drs. S.E. Lee, Y.-J. Kim, H.-Y. Lee, Yang and Oh participated in data analysis and interpretation. Drs. C.-G. Park, J.-J. Kim, S.-K. Kim, Rhee, and Oh participated in study design and acquisition of data. All of the authors participated in drafting the article or revising it and approved the final version. The funding body had no role in the analysis, interpretation, or writing of the manuscript from the data.Principal investigators and sites are as follows: Taehoon Ahn, MD, Gil Hospital, Gachon University of Medicine and Science, Incheon; Jang-Ho Bae, MD, Konyang University Hospital, Daejeon; Jei Keon Chae, MD, Chonbuk National University Hospital, Jeonju; Myeong Chan Cho, MD, Chungbuk University Hospital, Cheongju; Dongju Choi, MD, Seoul National University Bundang Hospital, Seongnam; Seung Ho Hur, MD, Dongsan Medical Center, Keimyung University College of Medicine, Daegu; Jin-Ok Jeong, MD, Chungnam University Hospital, Daejeon; Jin Ho Kang, MD, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul; Seok-Min Kang, MD, Yonsei Cardiovascular Center, Yonsei University College of Medicine, Seoul; Jun Kwan, MD, Inha University Hospital, Inchoen; Seung-Hwan Lee, MD, Wonju Christian Hospital, Yonsei University Wonju College of Medicine, Wonju; Jeong Bae Park, MD, Cheil General Hospital, Kwandong University College of Medicine, Seoul; Jong-Seon Park, MD, Yeungnam University Hospital, Daegu; Se-Joong Rim, MD, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul; Kyu-Hyung Ryu, MD, Konkuk University Medical Center, Seoul; Ki-Bae Seung, MD, and Ho-Joong Youn, MD, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul; Joon-Han Shin, MD, Ajou University Hospital, Suwon; and Jidong Sung, MD, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea