Efficacy and safety of the dual L- and T-type calcium channel blocker, ACT-280778: a proof-of-concept study in patients with mild-to-moderate essential hypertension

Act-280778 is an oral, non-dihydropyridine, dual l-/t-type calcium channel blocker. this phase 2a, double-blind, randomized, placebo- and active-controlled study investigated the efficacy and safety of 10 mg act-280778. patients with mild-to-moderate essential hypertension received once-daily placebo (n=53), act-280778 10 mg (n=52) or amlodipine 10 mg (n=54) for 4 weeks. the primary end point was the change from baseline to week 4 in placebo-adjusted mean trough sitting diastolic blood pressure (sidbp) with act-280778. tolerability was assessed by recording treatment-emergent adverse events (teaes). baseline clinical characteristics were similar across groups. no significant difference was observed at week 4 in mean trough sidbp between placebo (−9.9 (95% confidence limit (cl) −12.7, −7.0) mm hg) and act-280778 (−9.5 (−12.4, −6.5) mm hg; p=0.86); amlodipine reduced mean trough sidbp by −16.8 (−19.0, −14.5) mm hg, confirming assay validity. change in mean pr interval at week 4 (pre-dose) differed between placebo (−1.0 (95% cl −4.4, 2.3) ms) and act-280778 (6.5 (3.5, 9.6) ms); amlodipine did not increase pr interval (1.1 (−1.6, 3.9) ms).treatment-emergent adverse events (teae) frequency was 32.1% (placebo), 32.7% (act-280778) and 33.3% (amlodipine). the most common teaes were headache, peripheral edema, hypertension and second-degree atrioventricular block. act-280778 (10 mg) did not lower blood pressure in mild-to-moderate hypertension.