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Safety and Tolerability of Neladenoson Bialanate, a Novel Oral Partial Adenosine A1 Receptor Agonist, in Patients With Chronic Heart Failure.

Authors
  • Voors, Adriaan Alexander1
  • Düngen, Hans-Dirk2
  • Senni, Michele3
  • Nodari, Savina4
  • Agostoni, Piergiuseppe5
  • Ponikowski, Piotr6
  • Bax, Jeroen J7
  • Butler, Javed8
  • Kim, Raymond J9
  • Dorhout, Bernard1
  • Dinh, Wilfried10
  • Gheorghiade, Mihai11
  • 1 Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. , (Netherlands)
  • 2 Department of Cardiology, Campus Virchow, Charite Universitätsmedizin Berlin, Berlin, Germany. , (Germany)
  • 3 Cardiovascular Department, Ospedale Papa Giovanni XXIII, Bergamo, Italy. , (Italy)
  • 4 Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University and Civil Hospital of Brescia, Brescia, Italy. , (Italy)
  • 5 Centro Cardiologico Monzino, Milan, Italy. , (Italy)
  • 6 Wroclaw Medical University, Wroclaw, Poland. , (Poland)
  • 7 Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands. , (Netherlands)
  • 8 Division of Cardiology, Stony Brook University, Stony Brook, NY, USA.
  • 9 Duke Cardiovascular Magnetic Resonance Center, Duke University Medical Center, Durham, NC, USA.
  • 10 Department of Cardiology, Witten, Germany; Drug Discovery, Clinical Sciences, Bayer Pharma AG, Witten University, Wuppertal, Germany. , (Germany)
  • 11 Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Type
Published Article
Journal
Journal of clinical pharmacology
Publication Date
Apr 01, 2017
Volume
57
Issue
4
Pages
440–451
Identifiers
DOI: 10.1002/jcph.828
PMID: 27624622
Source
Medline
Keywords
License
Unknown

Abstract

We studied safety and tolerability of neladenoson bialanate, a novel oral selective partial adenosine A1 receptor agonist that maintains the cardioprotective effects of adenosine without the undesired side effects of a full agonist, in 2 pilot studies in patients with heart failure with reduced ejection fraction (HFrEF). The β-blocker interaction study was a single-blind, placebo-controlled study on the effects of a 30-mg single dose of neladenoson bialanate on atrioventricular (AV) conduction in 11 patients with HFrEF treated with β-blockers. The PARSiFAL pilot study was a double-blind, placebo-controlled study on the effects of a 7-day treatment with 10 or 20 mg neladenoson bialanate or placebo in 31 patients with HFrEF on β-blocker therapy. In the β-blocker interaction study with 11 HFrEF patients, no second- or third-degree AV block was detected on 48-hour Holter monitoring. In the 31 HFrEF patients included in the PARSiFAL pilot study, no second- or third-degree AV blocks were observed during 24-hour Holter monitoring, and no effects were seen on heart rate and blood pressure. Median absolute changes in LVEF, measured by cardiac magnetic resonance, were 1.9% (interquartile range -1.1 to 4.3), 0.3% (-1.4 to 2.7), and 2.2% (0.4 to 4.5), in the placebo, 10-mg, and 20-mg groups, respectively. Treatment of HFrEF patients with the novel partial adenosine A1 agonist neladenoson bialanate appeared to be safe in 2 small pilot studies, and no atrioventricular conduction disorders or neurological side effects were observed. No significant early changes in cardiac function were detected.

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