US-based Cardioxyl Pharmaceuticals has started dosing the first cohort of patients in a Phase I clinical study of CXL-1427, a new nitroxyl (HNO) prodrug optimised for clinical development as a potential treatment for acute decompensated heart failure (ADHF).
Around 110 healthy volunteers will be enrolled in the randomised, double-blind, placebo-controlled ascending dose evaluation trial that will evaluate the safety and pharmacokinetics of 24 and 48-hour infusions of CXL-1427.
The trial’s primary objective is to assess the safety and tolerability of continuous intravenous infusions of CXL-1427 for up to 48-hours in healthy volunteers.
Cardioxyl Pharmaceuticals chief medical officer ShiYin Foo said: "We are excited to advance this second-generation nitroxyl prodrug into the clinic and believe that CXL-1427 has the potential to be an important new therapy for patients with ADHF."
The Phase I study of CXL-1427 is set to be conducted over the first half of 2014.
Following successful completion of the Phase I trial, the company intends to start subsequent trials of CXL-1427 in patients with ADHF.
In the US, ADHF is the leading diagnosis for patients at the time of discharge from hospitals and the most common cause of hospitalisation for patients over 65 years of age.
The company said that despite the prevalence and severity of the condition, the treatment options available for patients with ADHF remain limited.
CXL-1427 is a second-generation prodrug that breaks down chemically to produce nitroxyl (HNO) and an inactive byproduct following intravenous administration.
According to the pre-clinical data and a Phase IIa human proof of concept study with Cardioxyl’s first-generation prodrug, HNO has been shown to produce a unique and very attractive haemodynamic profile.
The new combination of effects produced by the company’s HNO prodrugs differentiate them from other drugs currently used in the treatment of congestive heart failure.
Image: CXL-1427 has the potential to be an important new therapy for patients with ADHF. Photo: courtesy of freedigitalphotos.net.