A Phase 2a dose-escalation study of the safety, tolerability, pharmacokinetics and haemodynamic effects of BMS-986231 in hospitalized patients with heart failure with reduced ejection fraction
Tita C, Gilbert EM, Van Bakel AB, Grzybowski J, Haas GJ, Jarrah M, Dunlap SH, Gottlieb SS, Klapholz M, Patel PC, Pfister R, Seidler T, Shah KB, Zielinski T, Venuti RP, Cowart D, Foo SY, Vishnevsky A, Mitrovic V. A Phase 2a dose-escalation study of the safety, tolerability, pharmacokinetics and haemodynamic effects of BMS-986231 in hospitalized patients with heart failure with reduced ejection fraction. Eur J Heart Fail. 2017 Oct;19(10):1321-1332.
European journal of heart failure : journal of the Working Group on Heart Failure of the European Society of Cardiology
AIMS: This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS-986231, a novel second-generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF).
METHODS AND RESULTS: Forty-six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose-escalation cohorts in this double-blind, randomized, placebo-controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.5 L/min/m
CONCLUSIONS: BMS-986231 demonstrated a favourable safety and haemodynamic profile in patients hospitalized with advanced heart failure. Based on preclinical data and these study's findings, it is possible that the haemodynamic benefits may be mediated by inotropic and/or lusitropic as well as vasodilatory effects. The therapeutic potential of BMS-986231 should be further assessed in patients with heart failure.
Medical Subject Headings
Cardiovascular Agents; Dose-Response Relationship, Drug; Double-Blind Method; Heart Failure; Hemodynamics; Hospitalization; Humans; Nitric Oxide Donors; Stroke Volume; Treatment Outcome