Results will be included in the BYDUREON™ New Drug Application Resubmission in the Third Quarter of 2011….
Eli Lilly today announced results from a thorough QT (tQT) study that assessed the potential of exenatide to increase the QT interval across a wide range of plasma concentrations. The study was conducted to satisfy a requirement by the U.S. Food and Drug Administration (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. Further, the study found no relationship between QTc interval and plasma exenatide concentrations.
The QT interval represents the amount of time the heart’s electrical system takes to repolarize, or recharge, after each beat (i). As prolongation of the QT interval may increase the risk for cardiac arrhythmias, the FDA requires a tQT study for most new drugs in development. A tQT study is a specialized clinical trial designed to assess whether an investigational medication has the potential to prolong the QT interval.
“The findings of this tQT study are clear. Exenatide did not lead to QT prolongation, even at very high concentrations in the blood,” said Christian Weyer, M.D., senior vice president, research and development, Amylin Pharmaceuticals. “This study was designed in accordance with existing guidelines and in consultation with the FDA. We are confident in these results and will continue to work toward making BYDUREON available to patients in the U.S. as soon as possible.”
In its October 2010 complete response letter, 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, designed in accordance with the FDA’s published guidance on clinical evaluation of QT/QTc interval (ICH E14), compared the effects of exenatide at or above therapeutic concentrations to placebo on the QT interval in approximately 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 percent 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. The companies plan to present the full data set at a major medical meeting and submit the data for publication.
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 once-weekly formulation of exenatide, the active ingredient in BYETTA® (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.
Eli Lilly/Amylin Press release July 7, 2011