Comparative Efficacy and Safety Profile of Amlodipine 5 mg/Losartan 50 mg Fixed-Dose Combination and Amlodipine 10 mg Monotherapy in Hypertensive Patients Who Respond Poorly to Amlodipine 5 mg Monotherapy: An 8-Week, Multicenter, Randomized, Double-Blind Phase III Noninferiority Study

Seok Min Kang, Jong Chan Youn, Shung Chull Chae, Chang Gyu Park, Joo Young Yang, Moo Hyun Kim, Taek Jong Hong, Cheol Ho Kim, Jae Joong Kim, Dong Gu Shin, Jin Won Jung, Jung Han Yoon, Si Hoon Park, Jun Kwon, Seung Yun Cho

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Background: The number of hypertensive patients achieving treatment targets is not ideal with therapies that engage a single mechanism of action, and combination therapies using different mechanisms of action can increase drug efficacy in a synergistic way. Objective: This noninferiority study compared the clinical efficacy and safety profile of fixed-dose combination of amlodipine/losartan 5/50 mg and amlodipine 10 mg monotherapy in essential hypertensive patients who respond poorly to amlodipine 5 mg monotherapy. Methods: This was a double-blind, multicenter, randomized trial of hypertensive patients (N = 185) aged ≥18 years taking amlodipine 5 mg during the run-in treatment period but failed to achieve sitting diastolic blood pressure (DBP) <90 mm Hg. After randomization into the amlodipine/losartan 5/50 mg fixed-dose combination group (n = 92) and the amlodipine 10 mg monotherapy group (n = 93), treatment was maintained without dose escalation for 8 weeks. The noninferiority margin was prespecified as 4 mm Hg after 8 weeks of treatment for the difference of the average change in DBP between treatments. The primary efficacy evaluation of noninferiority was tested using a confidence interval approach with a 97.5% 1-sided lower confidence limit using the average difference in DBP measured at baseline and 8 weeks. Results: After 8 weeks, the DBP of both groups decreased from baseline by 8.9 (6.1) and 9.4 (7.5) mm Hg, respectively (difference = -0.5 [6.9] mm Hg, 95% CI: -2.5 to 1.5). Secondary end points of reductions in DBP after 4 weeks (-8.1 [6.7] vs -9.9 [7.3] mm Hg, difference = -1.8 mm Hg, 95% CI: -3.9 to 0.2) and sitting systolic blood pressure after 4 (-10.2 [11.8] vs -12.8 [10.2] mm Hg, difference = -2.6 mm Hg, 95% CI: -5.9 to 0.6) and 8 weeks (-12.2 [11.0] vs -13.4 [11.3] mm Hg, difference = -1.2 mmHg, 95% CI: -4.4 to 2.1) were comparable between the 2 treatment groups. There were 38 adverse events in 20 patients (21.7%) in the amlodipine/losartan 5/50 mg fixed-dose combination group and 31 in 24 patients (26.1%) in the amlodipine 10 mg monotherapy group; most were mild. There were 7 adverse events in 6 patients (6.5%) related to treatment in the fixed-dose combination group and 13 in 10 patients (10.9%) in the monotherapy group (P = 0.30). Conclusions: Fixed-dose combination amlodipine/losartan 5/50 mg was not inferior in terms of reductions in DBP after 8 weeks of treatment and had comparable safety profile to amlodipine 10 mg in patients who did not respond to amlodipine 5 mg monotherapy. identifier: NCT00940667.

Original languageEnglish
Pages (from-to)1953-1963
Number of pages11
JournalClinical Therapeutics
Issue number12
Publication statusPublished - 2011 Dec 1


All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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