EXamination of CArdiovascular OutcoMes with AlogliptIN versus Standard of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome (EXAMINE)

A cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome

William B. White, George L. Bakris, Richard M. Bergenstal, Christopher P. Cannon, William Cushman, Penny Fleck, Simon Heller, Cyrus Mehta, Steven E. Nissen, Alfonso Perez, Craig Wilson, Faiez Zannad

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Comprehensive safety evaluation of new drugs for diabetes mellitus is needed in the area of cardiovascular (CV) outcomes, particularly in populations with high CV risk. Alogliptin, a dipeptidyl peptidase 4 inhibitor, is under development for the treatment of type 2 diabetes mellitus alone or in combination with other antidiabetic therapies. Long-term CV safety of alogliptin is being established in a randomized, placebo-controlled clinical study in patients with acute coronary syndrome (ACS) using an analytical approach that has both an interim and final assessment. The primary CV end point for this trial is a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Approximately 5,400 men and women with type 2 diabetes and ACS (acute myocardial infarction or unstable angina) are being recruited and will be followed up for up to 4.5 years postrandomization. The statistical plan for the trial uses a design that evaluates the hazard ratio (HR) of alogliptin to placebo first based on the primary CV composite end point after accrual of 80 to 150 primary CV events and again when there are 550 to 650 primary CV events. In the first series of analyses, the upper bound of a group-sequential 1-sided repeated CI for the HR must be ≤1.8 for registration in the United States. At end of study, the upper bound of a subsequent group-sequential 1-sided repeated CI for the HR must be ≤1.3. For both group sequential analyses, the repeated CIs are calculated to insure simultaneous coverage probabilities of 97.5% for the true HR. Study progress: More than 2,000 ACS patients were randomized as of June 2011. EXAMINE will define the CV safety profile of this dipeptidyl peptidase 4 inhibitor in patients at high risk for CV events.

Original languageEnglish (US)
JournalAmerican Heart Journal
Volume162
Issue number4
DOIs
StatePublished - Jan 1 2011

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Dipeptidyl-Peptidase IV Inhibitors
Standard of Care
Acute Coronary Syndrome
Type 2 Diabetes Mellitus
Safety
Myocardial Infarction
Placebos
Drug Evaluation
Unstable Angina
Hypoglycemic Agents
Diabetes Mellitus
Stroke
Therapeutics
Population
alogliptin

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

EXamination of CArdiovascular OutcoMes with AlogliptIN versus Standard of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome (EXAMINE) : A cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome. / White, William B.; Bakris, George L.; Bergenstal, Richard M.; Cannon, Christopher P.; Cushman, William; Fleck, Penny; Heller, Simon; Mehta, Cyrus; Nissen, Steven E.; Perez, Alfonso; Wilson, Craig; Zannad, Faiez.

In: American Heart Journal, Vol. 162, No. 4, 01.01.2011.

Research output: Contribution to journalArticle

White, William B. ; Bakris, George L. ; Bergenstal, Richard M. ; Cannon, Christopher P. ; Cushman, William ; Fleck, Penny ; Heller, Simon ; Mehta, Cyrus ; Nissen, Steven E. ; Perez, Alfonso ; Wilson, Craig ; Zannad, Faiez. / EXamination of CArdiovascular OutcoMes with AlogliptIN versus Standard of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome (EXAMINE) : A cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome. In: American Heart Journal. 2011 ; Vol. 162, No. 4.
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abstract = "Comprehensive safety evaluation of new drugs for diabetes mellitus is needed in the area of cardiovascular (CV) outcomes, particularly in populations with high CV risk. Alogliptin, a dipeptidyl peptidase 4 inhibitor, is under development for the treatment of type 2 diabetes mellitus alone or in combination with other antidiabetic therapies. Long-term CV safety of alogliptin is being established in a randomized, placebo-controlled clinical study in patients with acute coronary syndrome (ACS) using an analytical approach that has both an interim and final assessment. The primary CV end point for this trial is a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Approximately 5,400 men and women with type 2 diabetes and ACS (acute myocardial infarction or unstable angina) are being recruited and will be followed up for up to 4.5 years postrandomization. The statistical plan for the trial uses a design that evaluates the hazard ratio (HR) of alogliptin to placebo first based on the primary CV composite end point after accrual of 80 to 150 primary CV events and again when there are 550 to 650 primary CV events. In the first series of analyses, the upper bound of a group-sequential 1-sided repeated CI for the HR must be ≤1.8 for registration in the United States. At end of study, the upper bound of a subsequent group-sequential 1-sided repeated CI for the HR must be ≤1.3. For both group sequential analyses, the repeated CIs are calculated to insure simultaneous coverage probabilities of 97.5{\%} for the true HR. Study progress: More than 2,000 ACS patients were randomized as of June 2011. EXAMINE will define the CV safety profile of this dipeptidyl peptidase 4 inhibitor in patients at high risk for CV events.",
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