Efficacy and Tolerability of Combination Therapy Versus Monotherapy with Candesartan and/or Amlodipine for Dose Finding in Essential Hypertension: A Phase II Multicenter, Randomized, Double-blind Clinical Trial

Il Suk Sohn, Chong Jin Kim, Taehoon Ahn, Ho Joong Youn, Hui Kyung Jeon, Sang Hyun Ihm, Eun Joo Cho, Woo Baek Chung, Shung Chull Chae, Woo Shik Kim, Chang Wook Nam, Seong Mi Park, Ji Yong Choi, Young Kwon Kim, Taek Jong Hong, Hae Young Lee, Jang Hyun Cho, Eun Seok Shin, Jung Han Yoon, Tae Hyun YangMyung Ho Jeong, Jun Hee Lee, Joong Il Park

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5 Citations (Scopus)

Abstract

Purpose Intensive blood pressure (BP) lowering is important for the treatment of hypertension; however, it has been a challenge to achieve target BP in many patients. The purpose of this study was to explore the optimal dosage of a fixed-dose combination of candesartan cilexetil (CAN) and amlodipine besylate (AML), by examining the tolerability and efficacy of CAN/AML combination therapy compared with those of monotherapy with either drug in patients with essential hypertension. Methods This Phase II multicenter, randomized, double-blind clinical trial enrolled patients aged 19 years or older with essential hypertension, defined as a mean sitting diastolic BP (msDBP) between 95 and 115 mm Hg, and a mean sitting systolic BP (msSBP) of <200 mm Hg after a 2-week placebo run-in period. A total of 635 patients were screened, of whom 439 were randomized to receive treatment; 425 patients were included in the full analysis set (combination therapy, 212; monotherapy, 213). Participants were randomly assigned to receive 1 of 8 treatments: CAN (8 or 16 mg), AML (5 or 10 mg), CAN/AML (8 mg/5 mg, 8 mg/10 mg, 16 mg/5 mg, or 16 mg/10 mg), once daily for 8 weeks. Findings After 8 weeks of treatment, changes in msDBP were significantly greater in the groups receiving CAN/AML combination therapies compared with monotherapies at matched doses, with the exception of CAN 8 mg/AML 10 mg versus AML 10 mg. The response to treatment and the achievement of target BP (both msSBP and msDBP) at week 8 were significantly greater overall in the groups that received combination therapy versus monotherapy. All medications were relatively well tolerated in each group. Implications Eight-week administration of CAN/AML (8 mg/5 mg, 16 mg/5 mg, and 16 mg/10 mg) resulted in a significantly greater BP reduction than that with CAN or AML monotherapy, and was determined to be well tolerated. ClinicalTrials.gov identifier: NCT02944734.

Original languageEnglish
Pages (from-to)1628-1638
Number of pages11
JournalClinical Therapeutics
Volume39
Issue number8
DOIs
Publication statusPublished - 2017 Aug

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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    Sohn, I. S., Kim, C. J., Ahn, T., Youn, H. J., Jeon, H. K., Ihm, S. H., Cho, E. J., Chung, W. B., Chae, S. C., Kim, W. S., Nam, C. W., Park, S. M., Choi, J. Y., Kim, Y. K., Hong, T. J., Lee, H. Y., Cho, J. H., Shin, E. S., Yoon, J. H., ... Park, J. I. (2017). Efficacy and Tolerability of Combination Therapy Versus Monotherapy with Candesartan and/or Amlodipine for Dose Finding in Essential Hypertension: A Phase II Multicenter, Randomized, Double-blind Clinical Trial. Clinical Therapeutics, 39(8), 1628-1638. https://doi.org/10.1016/j.clinthera.2017.06.014