AstraZeneca and Targacept, Inc announced that results from the phase-IIb clinical trial of AZD3480 (TC-1734) conducted by AstraZeneca in mild to moderate Alzheimer's disease were inconclusive.

In the 12-week placebo-controlled study, known as the Sirocco trial, neither the active comparator donepezil nor AZD3480 met the trial's criteria for statistical significance on the primary outcome measure, ADAS-Cog (Alzheimer's Disease Assessment Scale - Cognition Subscale). Both results were impacted by an improvement in the placebo group.

At two of the three doses tested, AZD3480 showed an improvement on the secondary outcome measures ADCS-CGIC (Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change, a seven-point scale), a widely accepted measure of clinician assessment of change in patients' behaviour and ability to function, and MMSE (Mini Mental State Examination, a 30-point scale), a quantitative cognition scale commonly used by neurologists in a clinical setting. Of the three AZD3480 doses, the middle dose performed best on both measures (0.5 point improvement, ADCS-CGIC and 0.9 point improvement, MMSE). Donepezil also showed an improvement on ADCS-CGIC (0.2 point improvement) and the MMSE (1.0 point improvement). Neither donepezil nor AZD3480 showed improvement in any domain of the Cognitive Drug Research computerized test battery in the pooled dataset of all subjects.

AZD3480 exhibited an overall safety and tolerability profile comparable to placebo in the trial, with fewer gastrointestinal-related adverse events (diarrhoea, nausea and vomiting) than donepezil.

Analyses of the full dataset from the Sirocco trial are ongoing. AstraZeneca and Targacept plan to discuss the data with leading medical experts and to present and publish more detailed results over the coming months. A decision by AstraZeneca with respect to potential further development of AZD3480 is expected in December 2008.

"While we had hoped for a more conclusive overall outcome, we believe the Sirocco trial provides further support for the clinical rationale for AZD3480 by demonstrating improvement on both ADCS-CGIC, an accepted scale that reflects improvement in everyday activities, and the widely used MMSE cognitive assessment, as well as a favourable safety and tolerability profile," said J Donald deBethizy, president and chief executive officer of Targacept. "These findings also strengthen the scientific foundation for our pipeline of NNR Therapeutics. We thank AstraZeneca for its execution of this trial and investment in the broad development of AZD3480."

In addition to Alzheimer's disease, AZD3480 is currently being evaluated in a phase-IIb trial in cognitive dysfunction in schizophrenia (the HALO trial), as well as a phase-II exploratory study in adult attention deficit/hyperactivity disorder. Top-line results from the cognitive dysfunction in schizophrenia trial are expected by the end of 2008.

AstraZeneca is a major international healthcare business engaged in research, development, manufacturing and marketing of prescription pharmaceuticals and supplier for healthcare services.

Targacept is a clinical-stage biopharmaceutical company that discovers and develops NNR Therapeutics, a new class of drugs for the treatment of central nervous system diseases and disorders.