Takeda Pharmaceutical Company Limited and its U.S. subsidiary Takeda Global Research & Development Center in Deerfield, Ill., have received notification that the FDA has agreed to the study design for EXAMINE, a cardiovascular outcomes trial for alogliptin, a selective dipeptidyl peptidase IV inhibitor under investigation for the treatment of type 2 diabetes as an adjunct to diet and exercise.
The new drug application for alogliptin was submitted in December 2007, and rejected on June 26, due to the FDA 's request for additional cardiovascular safety trial that satisfies the criteria outlined in the December 2008 "Guidance for Industry: Diabetes Mellitus -- Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes."
The Osaka, Japan-based company said that EXAMINE (EXamination of cArdiovascular outcoMes: alogliptIN vs. standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome) was designed to comply with this guidance.
According to the company, it will be a multicenter, randomized, double-blind, placebo-controlled study to evaluate cardiovascular outcomes following treatment with alogliptin in addition to standard of care in subjects with type 2 diabetes and acute coronary syndrome. It is schedule to begin in September and conclude December 2014, enrolling approximately 5,400 patients. It will take place in approximately 1,000 sites in the U.S., Europe and Asia.
The primary outcome is time from randomization to the occurrence of the primary major adverse cardiac events, defined as a composite of cardiovascular death, nonfatal MI and nonfatal stroke. The secondary outcome is time from randomization to the occurrence of the secondary major adverse cardiac events defined as a composite of cardiovascular death, nonfatal MI, nonfatal stroke and urgent revascularization due to unstable angina.
“While this trial is dependent on the occurrence of CV events, at this point we anticipate that we will be able to submit interim results to the FDA approximately two years after the study begins that will meet the FDA Guidance criteria for drug approval,” said Nancy Joseph-Ridge, MD, general manager of the pharmaceutical development division.