microscopic evidence of cardiotoxicity and did not see evidence of adverse
electrophysiologic or hemodynamic effects of Saxagliptin. In our phase 1 clinical
program, we studied Saxagliptin at doses up to 80x the proposed usual clinical dose. We
did not see an adverse effect on lipid parameters, blood pressure, heart rate, or QT
interval. For another member of the DPP-4 class, currently approved for clinical use in
the United States, published data indicated no meaningful differences in the incidence
rates for cardiac related or ischemia related adverse experiences. Thus the data available
to us prior to our analyses of the phase 2b, phase 3 clinical program did not suggest that
CV risk would be associated with Saxagliptin.
methods was to assess the consistency of our results given the retrospective nature of
many of our assessments. We use endpoints and methods defined by both us and by the
agency. I would now like to provide some context for our assessment of CV safety in the
phase 2b/phase 3 clinical programs.
in the Saxagliptin clinical program. While we analyze CV events defined by us and by
the Agency it is important to know if the analyses of these events were based upon a
common database and common analytic methods. For all pooled analyses we use
In non-clinical studies performed on multiple species, we did not see
I will now provide an overview of the methods used to analyze CV events
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our overview, we analyzed acute CV events prior to submitting the NDA for
Saxagliptin. We also retrospectively applied FDA guidance on evaluating CV risks to the
clinical data for Saxagliptin by assessing multiple additional types of CV events utilizing
multiple analytic methods.
The intent at using multiple types of CV events and multiple analytic