AZD3480 did not meet the trial’s criteria for statistical significance on the primary endpoints, improvement on various cognitive domains measured by the IntegNeuro computerized test battery. AZD3480 was generally well tolerated in the study. AstraZeneca and Targacept do not expect to progress AZD3480 into Phase III studies for cognitive dysfunction in schizophrenia.
The Phase IIb Halo trial was conducted by AstraZeneca under the terms of an exclusive global license and research collaboration agreement. The trial was a multi-center, randomized, double blind, placebo controlled, dose-finding study conducted at approximately 70 enrolling sites in the US and Canada.
Subjects (n = 445) between 18 and 55 years of age who were active smokers and taking medication from the class of drugs known as atypical anti-psychotics were randomly assigned to one of three dose groups of AZD3480 or to placebo and dosed over a 12-week period. The primary outcome measures of the trial were change from baseline after 12 weeks on various domains of cognition as measured by the IntegNeuro computerized test battery.
In addition to the Halo trial, AstraZeneca and Targacept previously announced top-line results from a Phase IIb study of AZD3480 in mild to moderate Alzheimer’s disease, known as the Sirocco trial, and are currently evaluating AZD3480 in a Phase II exploratory study in attention deficit/hyperactivity disorder (ADHD) in adults. A decision by AstraZeneca with respect to potential further development of AZD3480 in Alzheimer’s disease or ADHD is now expected in the first half of 2009, pending completion of the adult ADHD study and other ongoing evaluations.
Targacept and AstraZeneca also have announced that the lead compound arising out of the parties’ preclinical research collaboration is poised to enter the clinic. AstraZeneca plans by the end of 2008 to initiate a Phase I trial of AZD1446 (TC-6683), a product candidate selective for the alpha4beta2 neuronal nicotinic receptor. Under the terms of the parties’ collaboration agreement, AstraZeneca has agreed to make a $2 million milestone payment to Targacept.
Bob Holland, vice president and head of the neuroscience therapy area at AstraZeneca, said: While this trial outcome did not meet our objectives, we continue to pursue medicines that target neuronal nicotinic receptors with Targacept to treat cognitive disorders.