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Safety and Tolerability of the Chymase Inhibitor Fulacimstat in Patients With Left Ventricular Dysfunction After Myocardial Infarction-Results of the CHIARA MIA 1 Trial

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Düngen, Hans-Dirk ; Kober, Lars ; Nodari, Savina ; Schou, Morten ; Otto, Christiane ; Becka, Michael ; Kanefendt, Friederike ; Winkelmann, Bernhard R ; Gislason, Gunnar ; Richard, Frank ; Nielsen, Olav Wendelboe ; Gheorghiade, Mihai ; Senni, Michele. / Safety and Tolerability of the Chymase Inhibitor Fulacimstat in Patients With Left Ventricular Dysfunction After Myocardial Infarction-Results of the CHIARA MIA 1 Trial. I: Clinical Pharmacology in Drug Development. 2019 ; s. epub.

Bibtex

@article{d845319e372a4da792dbb7c7cc5718cc,
title = "Safety and Tolerability of the Chymase Inhibitor Fulacimstat in Patients With Left Ventricular Dysfunction After Myocardial Infarction-Results of the CHIARA MIA 1 Trial",
abstract = "The chymase inhibitor fulacimstat is developed as a first-in-class treatment option for the inhibition of adverse cardiac remodeling in patients with left ventricular dysfunction (LVD) after acute myocardial infarction (MI). The aim of the study was to examine the safety and tolerability of fulacimstat in patients with LVD after remote MI. A multicenter, multinational randomized, placebo-controlled study was performed in clinically stable patients (40-79 years of age, left ventricular ejection fraction ≤ 45{\%} because of MI in medical history) who were on stable evidence-based standard-of-care therapies for LVD post-MI including an angiotensin converting enzyme inhibitor or angiotensin receptor blocker at doses of at least half the recommended target dose. Patients were treated for 2 weeks with either placebo (n = 12) or 4 different doses of fulacimstat (5 mg twice daily, n = 9; 10 mg twice daily, n = 9; 25 mg twice daily, n = 10; 50 mg once daily, n = 9). Fulacimstat was safe and well tolerated at all examined doses. There were no clinically relevant effects on vital signs or potassium levels compared with placebo treatment. Mean plasma concentrations of fulacimstat increased with the administered dose and reached exposures predicted to be therapeutically active. The safety profile and the absence of effects on blood pressure or heart rate in a chronic patient population having similar comorbidities and receiving similar comedication as patients after acute MI support future clinical trials with fulacimstat in patients after acute MI.",
author = "Hans-Dirk D{\"u}ngen and Lars Kober and Savina Nodari and Morten Schou and Christiane Otto and Michael Becka and Friederike Kanefendt and Winkelmann, {Bernhard R} and Gunnar Gislason and Frank Richard and Nielsen, {Olav Wendelboe} and Mihai Gheorghiade and Michele Senni",
note = "{\circledC} 2018, The American College of Clinical Pharmacology.",
year = "2019",
doi = "10.1002/cpdd.633",
language = "English",
pages = "epub",
journal = "Clinical Pharmacology in Drug Development",
issn = "2160-763X",
publisher = "Wiley-Blackwell Publishing Ltd",

}

RIS

TY - JOUR

T1 - Safety and Tolerability of the Chymase Inhibitor Fulacimstat in Patients With Left Ventricular Dysfunction After Myocardial Infarction-Results of the CHIARA MIA 1 Trial

AU - Düngen, Hans-Dirk

AU - Kober, Lars

AU - Nodari, Savina

AU - Schou, Morten

AU - Otto, Christiane

AU - Becka, Michael

AU - Kanefendt, Friederike

AU - Winkelmann, Bernhard R

AU - Gislason, Gunnar

AU - Richard, Frank

AU - Nielsen, Olav Wendelboe

AU - Gheorghiade, Mihai

AU - Senni, Michele

N1 - © 2018, The American College of Clinical Pharmacology.

PY - 2019

Y1 - 2019

N2 - The chymase inhibitor fulacimstat is developed as a first-in-class treatment option for the inhibition of adverse cardiac remodeling in patients with left ventricular dysfunction (LVD) after acute myocardial infarction (MI). The aim of the study was to examine the safety and tolerability of fulacimstat in patients with LVD after remote MI. A multicenter, multinational randomized, placebo-controlled study was performed in clinically stable patients (40-79 years of age, left ventricular ejection fraction ≤ 45% because of MI in medical history) who were on stable evidence-based standard-of-care therapies for LVD post-MI including an angiotensin converting enzyme inhibitor or angiotensin receptor blocker at doses of at least half the recommended target dose. Patients were treated for 2 weeks with either placebo (n = 12) or 4 different doses of fulacimstat (5 mg twice daily, n = 9; 10 mg twice daily, n = 9; 25 mg twice daily, n = 10; 50 mg once daily, n = 9). Fulacimstat was safe and well tolerated at all examined doses. There were no clinically relevant effects on vital signs or potassium levels compared with placebo treatment. Mean plasma concentrations of fulacimstat increased with the administered dose and reached exposures predicted to be therapeutically active. The safety profile and the absence of effects on blood pressure or heart rate in a chronic patient population having similar comorbidities and receiving similar comedication as patients after acute MI support future clinical trials with fulacimstat in patients after acute MI.

AB - The chymase inhibitor fulacimstat is developed as a first-in-class treatment option for the inhibition of adverse cardiac remodeling in patients with left ventricular dysfunction (LVD) after acute myocardial infarction (MI). The aim of the study was to examine the safety and tolerability of fulacimstat in patients with LVD after remote MI. A multicenter, multinational randomized, placebo-controlled study was performed in clinically stable patients (40-79 years of age, left ventricular ejection fraction ≤ 45% because of MI in medical history) who were on stable evidence-based standard-of-care therapies for LVD post-MI including an angiotensin converting enzyme inhibitor or angiotensin receptor blocker at doses of at least half the recommended target dose. Patients were treated for 2 weeks with either placebo (n = 12) or 4 different doses of fulacimstat (5 mg twice daily, n = 9; 10 mg twice daily, n = 9; 25 mg twice daily, n = 10; 50 mg once daily, n = 9). Fulacimstat was safe and well tolerated at all examined doses. There were no clinically relevant effects on vital signs or potassium levels compared with placebo treatment. Mean plasma concentrations of fulacimstat increased with the administered dose and reached exposures predicted to be therapeutically active. The safety profile and the absence of effects on blood pressure or heart rate in a chronic patient population having similar comorbidities and receiving similar comedication as patients after acute MI support future clinical trials with fulacimstat in patients after acute MI.

U2 - 10.1002/cpdd.633

DO - 10.1002/cpdd.633

M3 - Journal article

SP - epub

JO - Clinical Pharmacology in Drug Development

JF - Clinical Pharmacology in Drug Development

SN - 2160-763X

ER -

ID: 56241171