A Randomized, Double-blind, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Fimasartan/Amlodipine Combined Therapy Versus Fimasartan Monotherapy in Patients With Essential Hypertension Unresponsive to Fimasartan Monotherapy

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• 作者：Kwang-il Kim¹ ; Mi-Seung Shin² ; Sang-Hyun Ihm³ ; Ho-Joong Youn⁴ ; Ki-Chul Sung⁵ ; Shung Chull Chae⁶ ; Chang-Wook Nam⁷ ; Hong Seog Seo⁸ ; Seong-Mi Park⁹ ; Moo-Yong Rhee¹⁰ ; Moo Hyun Kim¹¹ ; Kwang Soo Cha¹² ; Yong-Jin Kim¹³ ; Jae-Joong Kim¹⁴ ; Kook Jin Chun¹⁵ ; Byung-Su Yoo¹⁶ ; Sungha Park¹⁷ ; Eun-Seok Shin¹⁸ ; Dong-Soo Kim¹⁹ ; Doo Il Kim²⁰ ; Kye Hun Kim²¹ ; Seung-Jae Joo²² ; Jin-Ok Jeong²³ ; Jinho Shin²⁴ ; Cheol Ho Kim¹ ; ^{cheolkim@snu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：amlodipine ; angiotensin II type 1 receptor blockers ; antihypertensive ; blood pressure ; combination ; fimasartan
• 刊名：Clinical Therapeutics
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：38
• 期：10
• 页码：2159-2170
• 全文大小：335 K

文摘

The goal of this study was to evaluate whether the blood pressure–lowering efficacy of fimasartan/amlodipine combination therapy was superior to that of fimasartan monotherapy after 8 weeks of treatment in patients with hypertension who had failed to respond adequately to fimasartan monotherapy.

Methods

This trial was a randomized, double-blind, multicenter, Phase III clinical study. Patients who failed to respond after 4 weeks of treatment with 60 mg daily of fimasartan (sitting systolic blood pressure [SiSBP]) ≥140 mm Hg) were randomized to receive either daily fimasartan 60 mg or fimasartan/amlodipine 60 mg/10 mg. The primary efficacy end point was the change in SiSBP from baseline to week 8. Secondary end points included the change in SiSBP from baseline to week 4, the changes in sitting diastolic blood pressure from baseline to weeks 4 and 8, and the response rate (SiSBP <140 mm Hg or decrease in SiSBP ≥20 mm Hg) or control rate (SiSBP <140 mm Hg) at week 8. Treatment-emergent adverse events were also assessed.

Findings

Of 143 patients randomized to treatment, 137 patients who had available efficacy data were analyzed. The mean age of patients was 59.1 (8.9) years, and 100 (73.0%) were male. Baseline SiSBP and sitting diastolic blood pressure were 150.6 (9.2) mm Hg and 91.7 (8.6) mm Hg, respectively. In the fimasartan/amlodipine combination group, a greater reduction in SiSBP from baseline to week 8 was observed compared with the fimasartan group (7.8 [13.3] mm Hg in the fimasartan group vs 20.5 [14.6] mm Hg in the fimasartan/amlodipine group; P < 0.0001). This reduction was observed after 4 weeks. The mean SiSBP changes from baseline to week 4 were 8.1 (15.8) mm Hg in the fimasartan group and 20.1 (14.7) mm Hg in the fimasartan/amlodipine group (P < 0.0001). At week 8, the response rate was significantly higher in the fimasartan/amlodipine (82.1%) group than in the fimasartan (32.9%) group (P < 0.0001). The control rate at week 8 was also higher in the fimasartan/amlodipine (79.1%) group than in the fimasartan (31.4%) group (P < 0.0001). Adverse drug reactions were observed in 9 patients (6.3%), with no significant differences between treatment groups. There were no serious adverse events associated with the study drugs.

Implications

Fimasartan/amlodipine combination therapy exhibited superior efficacy in reducing blood pressure, with no increase in adverse drug reactions, compared with fimasartan monotherapy. ClinicalTrials.gov identifier: NCT02152306.