Study results support BYDUREON’s NDA
Amylin Pharmaceuticals, Eli Lilly and Alkermes announced results from QT (tQT) study of exenatide to increase the QT interval across a wide range of plasma concentrations. The study was conducted to satisfy a requirement by the FDA in support of the New Drug Application (NDA) for BYDUREON (exenatide extended-release for injectable suspension), an investigational medication for type 2 diabetes.
Using multiple heart rate correction methodologies, the study met the pre-specified primary endpoint, demonstrating that exenatide at and above therapeutic levels did not prolong the corrected QT (QTc) interval in healthy individuals. The study found no relationship between QTc interval and plasma exenatide concentrations.
The FDA requested a tQT study with exposures of exenatide at higher than typical therapeutic levels of BYDUREON, such as those that might be achieved in patients with impaired renal function. The companies plan to submit results of the tQT study to the FDA in the third quarter of 2011 as part of their reply to the complete response letter for the BYDUREON NDA.
This randomized, double-blind study compared the effects of exenatide at or above therapeutic concentrations to placebo on the QT interval in 75 healthy volunteers. The primary endpoint was to determine whether exenatide administered at therapeutic and supratherapeutic concentrations differed from placebo in the mean change in the QTc interval (defined as the upper bound of the 95% confidence interval for placebo-corrected, baseline subtracted QTc being <10 milliseconds). All heart rate correction methodologies that satisfied the pre-specified selection criteria, including QTcP, QTcF and QTcI, met the primary endpoint. Moxifloxacin, an antibiotic known to prolong the QT interval, was used as a positive control.
BYDUREON is the proposed brand name for exenatide extended-release for injectable suspension. It is an investigational medication for type 2 diabetes designed to deliver continuous therapeutic levels of exenatide in a single weekly dose. BYDUREON is a formulation of exenatide, the active ingredient in BYETTAR (exenatide) injection, which has been available in the U.S. since June 2005 and is used in more than 70 countries worldwide to improve glycemic control in adults with type 2 diabetes. BYDUREON received marketing authorization in the European Union in June 2011.