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

Purpose: 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. Patients and 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 and P<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. Conclusion: CKD-828 is an effective and safe option for patients with inadequate responses to S-amlodipine monotherapy.