Cardioxyl Pharmaceuticals, Inc. have announced the positive results of a clinical trial demonstrating that CXL-1427, a novel potential treatment for acute decompensated heart failure (ADHF), was well tolerated in healthy volunteers. The company has now initiated dosing of hospitalized patients with decompensated heart failure in a Phase IIa clinical trial designed to further evaluate the drug's safety and tolerability as well as its dosing levels.
The Phase I clinical trial evaluated the safety and tolerability of 24- and 48-hour continuous intravenous infusions of CXL-1427 in 80 healthy volunteers. The trial's results showed not only that CXL-1427 was well tolerated with limited adverse events, but also that it is clearly hemodynamically active. Cardioxyl's ongoing Phase IIa study is a randomized, double-blinded, placebo-controlled, invasive hemodynamic study designed to evaluate the safety, tolerability and hemodynamic effects of 6-hour intravenous infusions of CXL-1427 in hospitalized patients with advanced heart failure. It is being conducted at up to 34 clinical sites globally and will enroll approximately 48 hospitalized patients.
"We are very encouraged by the results seen in the first clinical trial for CXL-1427," said ShiYin Foo, M.D., Ph.D., Cardioxyl's Chief Medical Officer, "and we are excited to have begun our next stage of clinical testing in advanced heart failure patients. Heart failure patients have few effective options, and the pre-clinical and clinical data for CXL-1427 suggest that this could be an important new therapy for patients with ADHF."
Nitroxyl, the chemical name for HNO, has been studied for its potential as a treatment for heart failure. HNO dilates blood vessels and acts directly on the heart through a unique mechanism to safely enhance both systolic and diastolic function. Cardioxyl's proprietary platform of HNO technology has produced a number of candidate therapeutics for treating heart failure, including CXL-1427.
ADHF is the most severe form of heart failure and is the most common cause of hospitalization for patients over 65 years of age. A significant portion of the $39 billion spent annually to treat heart failure in the U.S. is directed at managing ADHF. Despite the prevalence and severity of the condition, the treatment options available for patients with ADHF remain limited.
CXL-1427 is a novel, improved second-generation prodrug that breaks down chemically to produce nitroxyl (HNO) and an inactive byproduct following intravenous administration. In extensive pre-clinical testing and in a Phase IIa human proof of concept study with Cardioxyl's first-generation prodrug, HNO was shown to produce a unique and very attractive hemodynamic profile. The novel combination of effects produced by Cardioxyl's HNO prodrugs distinguishes them from other therapies used in the treatment of congestive heart failure and provides a strong rationale for continuing the development of this important new class of drugs.