WILMINGTON, Del., Sept. 15 /PRNewswire-FirstCall/ --
-- Results inconclusive, as primary outcome measure not statistically
significant for either donepezil or AZD3480; results impacted by
improvement in placebo group
-- Improvements shown on secondary outcome measures ADCS-CGIC and MMSE
-- Overall safety and tolerability profile comparable to placebo, with
fewer GI-related AEs than donepezil
-- Next steps include further analysis of full dataset and planned
discussions with leading medical experts
AstraZeneca (NYSE: AZN) and Targacept, Inc. today 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 7-point scale), a widely
accepted measure of clinician assessment of change in patients' behavior
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
(diarrhea, 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 favorable safety and tolerability
profile," said J. Donald deBethizy, Ph.D., 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.
About the Study
The Phase IIb Sirocco 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 84 sites in Western Europe, Eastern Europe
and Canada. Subjects (n = 567) were between 60 and 85 years of age and
diagnosed with probable Alzheimer's disease that was classified, based on a
quantitative scale, as mild or moderate in severity. Subjects were assigned
to one of three dose groups of AZD3480, to an active comparator, donepezil,
or to placebo and dosed over 12 weeks. The primary outcome measure in the
trial was change from baseline after 12 weeks on ADAS-Cog. A number of
secondary outcome measures were also used in the trial.
About AstraZeneca
AstraZeneca is a major international healthcare business engaged in
research, development, manufacturing and marketing of prescription
pharmaceuticals and supplier for healthcare services. AstraZeneca is one of
the world's leading pharmaceutical companies with healthcare sales of US
$29.55 billion and is a leader in gastrointestinal, cardiovascular,
neuroscience, respiratory, oncology and infection product sales.
AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as
well as the FTSE4Good Index.
About Targacept
Targacept is a clinical-stage biopharmaceutical company that discovers
and develops NNR Therapeutics (TM), a new class of drugs for the treatment
of central nervous system diseases and disorders. Targacept's product
candidates selectively modulate neuronal nicotinic receptors that serve as
key regulators of the nervous system to promote therapeutic effects and
limit adverse side effects. Targacept has product candidates in development
for Alzheimer's disease, cognitive dysfunction in schizophrenia, pain and
major depressive disorder, as well as multiple preclinical programs.
Targacept also has a cognition-focused collaboration with AstraZeneca and a
strategic alliance with GlaxoSmithKline. Targacept's news releases are
available on its website at http://www.targacept.com.
SOURCE AstraZeneca
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