title: Efficacy and safety of two fixed-dose combinations of S-amlodipine and telmisartan (CKD-828) versus S-amlodipine monotherapy in patients with hypertension inadequately controlled using S-amlodipine monotherapy: an 8-week, multicenter, randomized, double-blind, Phase III clinical study.
abstract: OBJECTIVE
  To evaluate the blood pressure (BP) lowering efficacy and safety of CKD-828, a fixed-dose combination of S-amlodipine (the more active isomer of amlodipine besylate, which is calcium channel blocker) and telmisartan (long acting angiotensin receptor blocker), in patients with hypertension inadequately controlled with S-amlodipine monotherapy.
  
  
  METHODS
  Eligible patients (N=187) who failed to respond after 4-week S-amlodipine 2.5 mg monotherapy (sitting diastolic blood pressure [sitDBP] ≥90 mmHg) to receive CKD-828 2.5/40 mg (n=63), CKD-828 2.5/80 mg (n=63), or S-amlodipine 2.5 mg (n=61) for 8 weeks. The primary efficacy endpoint, mean sitDBP change from baseline to Week 8, was compared between the combination (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg) and S-amlodipine monotherapy groups. The safety was assessed based on adverse events, vital signs, and physical examination findings.
  
  
  RESULTS
  After the 8-week treatment, changes in sitDBP/systolic BP (SBP) were -9.67±6.50/-12.89±11.78, -10.72±6.19/-13.79±9.41, and -4.93±7.26/-4.55±11.27 mmHg in the CKD-828 2.5/40 mg (P<0.0001/P<0.0001), CKD-828 2.5/80 mg (P<0.0001/P<0.0001), and S-amlodipine 2.5 mg (P<0.0001/P=0.0027) groups, respectively, which were all significant BP reductions. At Week 8, the CKD-828 2.5/40 mg (sitDBP/SBP:P=0.0002/P<0.0001) and CKD-828 2.5/80 mg (sitDBP/SBP:P=0.0001/P<0.0001) showed superior BP-lowering effects to S-amlodipine 2.5 mg (P<0.001). At Week 4, all groups showed significant antihypertensive effects but both CKD-828 combinations (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg) exhibited superior BP-lowering effects to that of S-amlodipine 2.5 mg (sitDBP/SBP:P=0.0028/P=0.0001 andP<0.0001/P=0.0012, respectively). The adverse event incidence was significantly lower in the CKD-828 2.5/40 mg (9.52%,P=0.0086) than in the S-amlodipine 2.5 mg group (27.87%) and increasing the telmisartan dose induced no unexpected adverse events, suggesting the safety of CKD-828.
  
  
  CONCLUSIONS
  CKD-828 is an effective and safe option for patients with inadequate responses to S-amlodipine monotherapy.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea, Seoul.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Ihm
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea, Seoul.
authors.forename: Hui-Kyung
authors.initials: HK
authors.lastname: Jeon
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kosin University College of Medicine.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cha
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Pusan National University Hospital, Busan.
authors.forename: Taek-Jong
authors.initials: TJ
authors.lastname: Hong
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine, Seoul.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Cardiology, Soonchunhyang University Hospital, Bucheon.
authors.forename: Nae-Hee
authors.initials: NH
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Wonju College of Medicine, Yonsei University, Wonju.
authors.forename: Jung Han
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Cardiology, Chonnam National University Hospital, Gwangju.
authors.forename: Namsik
authors.initials: N
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Chungbuk National University, College of Medicine, Cheongju.
authors.forename: Kyung-Kuk
authors.initials: KK
authors.lastname: Hwang
authors.affiliation: Division of Cardiology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Jo
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea, Seoul.
authors.forename: Ho-Joong
authors.initials: HJ
authors.lastname: Youn
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000009:adverse effects / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D056910:Republic of Korea; D000077333:Telmisartan; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D002121:Calcium Channel Blockers; D004338:Drug Combinations; C548840:telmisartan amlodipine combination; D017311:Amlodipine; D000077333:Telmisartan
keywords: angiotensin receptor blocker; antihypertensive; blood pressure; calcium channel blocker; efficacy; safety