U.S. FDA agrees to the study design for cardiovascular outcomes trial of alogliptin

Takeda Pharmaceutical Company Limited ("Takeda") and Takeda Global Research & Development Center, Inc., a wholly owned United States (U.S.) subsidiary, today jointly announced that the latter has received notification that the U.S. Food and Drug Administration (FDA) has agreed to the study design for a cardiovascular (CV) outcomes trial titled EXAMINE (EXamination of CArdiovascular OutcoMes: AlogliptIN vs. Standard of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome) 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 alogliptin New Drug Application (NDA) was submitted in December 2007, and in the complete response for alogliptin dated June 26, 2009, the FDA requested an additional CV 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 EXAMINE study is designed to comply with this Guidance.

"Takeda received FDA agreement to the design of the CV study and we are pleased to move forward with the study and collecting additional safety data so that the FDA can continue the review of the alogliptin NDA," said Nancy Joseph-Ridge, M.D., General Manager, Pharmaceutical Development Division. "We are committed to conducting this study to satisfy the CV safety requirements, leading to the enhancement of the product profile of alogliptin. 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."

Outline of the EXAMINE Trial

Title: 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 Study Start: September 2009 Study Completion: December 2014 No. of Patients: Approximately 5,400 Primary Outcome: Time from randomization to the occurrence of the Primary Major Adverse Cardiac Events defined as a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke Secondary Outcome: Time from randomization to the occurrence of the Secondary Major Adverse Cardiac Events defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and urgent revascularization due to unstable angina Study Sites: Approximately 1,000 sites in the U.S., Europe, Asia