Safety and Tolerability of the Chymase Inhibitor Fulacimstat in Patients With Left Ventricular Dysfunction After Myocardial Infarction-Results of the CHIARA MIA 1 Trial.
Adult
Aged
Angiotensin Receptor Antagonists
/ therapeutic use
Angiotensin-Converting Enzyme Inhibitors
/ therapeutic use
Carboxylic Acids
/ administration & dosage
Chymases
/ antagonists & inhibitors
Drug Administration Schedule
Female
Heart Failure
/ etiology
Humans
Indenes
/ administration & dosage
Male
Middle Aged
Myocardial Infarction
/ complications
Pyrimidines
/ administration & dosage
Treatment Outcome
Ventricular Dysfunction, Left
/ drug therapy
BAY 1142524
chymase inhibitor
fulacimstat
left ventricular dysfunction
safety
tolerability
Journal
Clinical pharmacology in drug development
ISSN: 2160-7648
Titre abrégé: Clin Pharmacol Drug Dev
Pays: United States
ID NLM: 101572899
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
25
09
2018
accepted:
26
10
2018
pubmed:
20
11
2018
medline:
5
8
2020
entrez:
20
11
2018
Statut:
ppublish
Résumé
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.
Substances chimiques
Angiotensin Receptor Antagonists
0
Angiotensin-Converting Enzyme Inhibitors
0
Carboxylic Acids
0
Indenes
0
Pyrimidines
0
Chymases
EC 3.4.21.39
fulacimstat
VIR72PP4ZU
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
942-951Informations de copyright
© 2018, The American College of Clinical Pharmacology.
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