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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

Journal of Human Hypertension volume 29, pages 229–235 (2015)Cite this article

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Abstract

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.

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Acknowledgements

We thank Kim Croskery and Liz Bullock (Watermeadow Medical, Witney, UK) for their writing and editorial assistance, supported by Actelion Pharmaceuticals Ltd.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland

    J Dingemanse, K Shakeri-Nejad & M S Mueller

  2. Dedinje Cardiovascular Institute, University of Belgrade, Belgrade, Serbia

    P Otasevic

  3. Gefen Cardiac Health Centre, Givatayim and Israeli Academic College, Ramat‐Gan, Israel

    E Klainman

  4. Clinical Hospital Center Zemun, University of Belgrade, Belgrade, Serbia

    B Putnikovic

  5. Department of Biostatistics, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland

    H Kracker

  6. Wolfson Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    R Zimlichman

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  1. J Dingemanse
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Correspondence to J Dingemanse.

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Competing interests

This study was sponsored by Actelion Pharmaceuticals Ltd. Dr Dingemanse, Dr Shakeri-Nejad, Dr Kracker and Dr Mueller were employees and stockholders of Actelion Pharmaceuticals Ltd at the time the study was conducted. Dr Otasevic and Dr Zimlichman received honoraria from Actelion Pharmaceuticals Ltd for assistance with clinical trials, and Dr Klainman and Dr Putnikovic have no conflict of interest relevant to this manuscript.

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Dingemanse, J., Otasevic, P., Shakeri-Nejad, K. et al. 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. J Hum Hypertens 29, 229–235 (2015). https://doi.org/10.1038/jhh.2014.79

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