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A Phase 1 Randomized Study of Single Intravenous Infusions of the Novel Nitroxyl Donor BMS-986231 in Healthy Volunteers.

ABSTRACT: Nitroxyl (HNO) is a reactive nitrogen molecule that has potential therapeutic benefits for patients with acute heart failure. The results of the first-in-human study for BMS-986231, a novel HNO donor, are reported. The aim of this sequential cohort study was to evaluate the safety, tolerability, and pharmacokinetic profile of BMS-986231 after 24- and 48-hour intravenous infusions in healthy volunteers. Eighty subjects were randomized and dosed. Seven cohorts (stratum A) received BMS-986231 0.1, 0.33, 1, 3, 5, 10, and 15 ?g/kg/min or placebo, infused over 24 hours. An additional cohort (stratum B) received 10 ?g/kg/min or placebo, infused over 48 hours. Adverse events (AEs) were reported for 30 days after completion of infusion. Blood/urine samples were collected at regular intervals; other parameters (blood pressure, heart rate/rhythm, cardiac index) were also assessed. Headaches were the most commonly reported drug-related AE (48%) in those who received BMS-986231, although their severity was reduced by hydration. No other significant drug-related AEs were noted. BMS-986231 was associated with dose-dependent and well-tolerated reductions in systolic and diastolic blood pressure versus baseline; cardiac index, as measured noninvasively, was increased. BMS-986231 had no clinically significant effect on heart rate/rhythm or laboratory parameters. Its mean elimination half-life was 0.7-2.5 hours. BMS-986231 was safe and well-tolerated for up to 24 hours (15 ?g/kg/min) or 48 hours (10 ?g/kg/min), with a favorable hemodynamic profile observed. Ongoing studies continue to evaluate the potential benefit of BMS-986231 in patients with acute heart failure.

SUBMITTER: Cowart D

PROVIDER: S-EPMC6519195 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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A Phase 1 Randomized Study of Single Intravenous Infusions of the Novel Nitroxyl Donor BMS-986231 in Healthy Volunteers.

Cowart Douglas D Venuti Robert P RP Lynch Kim K Guptill Jeffrey T JT Noveck Robert J RJ Foo Shi Yin SY

Journal of clinical pharmacology 20190131 5

Nitroxyl (HNO) is a reactive nitrogen molecule that has potential therapeutic benefits for patients with acute heart failure. The results of the first-in-human study for BMS-986231, a novel HNO donor, are reported. The aim of this sequential cohort study was to evaluate the safety, tolerability, and pharmacokinetic profile of BMS-986231 after 24- and 48-hour intravenous infusions in healthy volunteers. Eighty subjects were randomized and dosed. Seven cohorts (stratum A) received BMS-986231 0.1, ...[more]

PMID: 30703258

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Dataset Information

A Phase 1 Randomized Study of Single Intravenous Infusions of the Novel Nitroxyl Donor BMS-986231 in Healthy Volunteers.

Publications

A Phase 1 Randomized Study of Single Intravenous Infusions of the Novel Nitroxyl Donor BMS-986231 in Healthy Volunteers.

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