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

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.

• Authors: Adriaan Alexander Voors, Hans-Dirk Düngen, Michele Senni, Savina Nodari, Piergiuseppe Agostoni, Piotr Ponikowski, Jeroen J Bax, Javed Butler, Raymond J Kim, Bernard Dorhout, Wilfried Dinh, Mihai Gheorghiade
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 57 Issue 4 Pg. 440-451 (04 2017) ISSN: 1552-4604 [Electronic] England
• PMID: 27624622 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2016, The American College of Clinical Pharmacology.

Chemical References

• Adenosine A1 Receptor Agonists

Topics

• Adenosine A1 Receptor Agonists (administration & dosage)
• Administration, Oral
• Aged
• Blood Pressure (drug effects, physiology)
• Chronic Disease
• Double-Blind Method
• Drug Partial Agonism
• Electrocardiography (drug effects, methods)
• Female
• Follow-Up Studies
• Heart Conduction System (drug effects, physiology)
• Heart Failure (diagnosis, drug therapy, physiopathology)
• Heart Rate (drug effects, physiology)
• Humans
• Male
• Middle Aged
• Pilot Projects
• Single-Blind Method