Australia-based Neuren Pharmaceuticals has recruited the first patient in its phase III clinical trial of its lead compound, Glypromate, which is used to reduce cognitive impairment in patients following cardiac surgery. The first patient was dosed at the Lindner Center in Cincinnati, Ohio, US. The Phase III trial represents a key milestone for Neuren as it progresses Glypromate towards commercialisation.
Almost 70 percent of patients who have cardiac surgery with cardiopulmonary bypass experience cognitive decline at discharge and up to 35 percent of patients? exhibit cognitive impairment three months after the operation. With nearly one million procedures performed annually in the US and other developed markets, more than 200,000 patients per year are left with persistent cognitive impairment. The goal of the trial is to reduce the level of cognitive decline and associated functional problems experienced by these patients.
During cardiac surgery with bypass, the patient?s heart is stopped and the blood flow is directed through a device called a heart lung machine that oxygenates the blood and pumps it through the body while the heart is stopped. During this time the aorta, the artery which normally carries oxygenated blood from the heart, is clamped shut. Many experts in this area believe that the small particles of fat and other material, called microemboli, released when the aorta is unclamped at the end of bypass are a primary cause of the brain damage that causes cognitive impairment. During the trial, Glypromate will be administered as a four-hour infusion beginning shortly after the heart is restarted and the aorta is unclamped.
Neuren believes that starting the infusion just at the point where brain damage is believed to occur will maximise the opportunity for the drug to protect the brain. There are currently no drugs approved to reduce cognitive impairment following cardiac surgery, representing a market potential estimated at more than $1 billion and an opportunity for Neuren?s Glypromate, once approved, to be the first available in the market.
The trial will involve approximately 600 patients across 24 sites in the United States, Australia and New Zealand. Clinical sites in Atlanta, Charleston and other US sites are expected to begin enrolling patients shortly, with enrolment to be completed by the end of 2008.
The majority of patients will be enrolled at sites in Australia and New Zealand, where Neuren will be monitoring and managing the double-blind, multi-centre, placebo-controlled trial. Change in cognitive function from before surgery to three months after surgery is a primary endpoint of the study and will be assessed using computerized software that combines 15 different standardized and well-validated tests to measure eight separate aspects of cognitive function called domains.
The US Food and Drug Administration (FDA) has allowed a review of data on the primary endpoints after 300 patients have been enrolled without un-blinding the study to evaluate variance and possibly increase the number of patients. This adaptive trial design is an important element of the FDA agreed study design as it reduces the risk of a negative outcome that could result from higher than expected variation in the test results independent of the effects of the drug.