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Cardiovascular Outcomes Study of Alogliptin in Patients With Type 2 Diabetes and Acute Coronary Syndrome (EXAMINE)

This study has been completed.
Information provided by (Responsible Party):
Takeda Identifier:
First received: August 28, 2009
Last updated: April 15, 2014
Last verified: April 2014
The purpose of this study is to evaluate the cardiovascular outcomes of alogliptin, once daily (QD), compared with placebo, in addition to standard of care, in patients with type 2 diabetes mellitus and acute coronary syndrome.

Condition Intervention Phase
Diabetes Mellitus, Type 2
Acute Coronary Syndrome
Drug: Alogliptin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:

Further study details as provided by Takeda:

Primary Outcome Measures:
  • Percentage of Participants With Primary Major Adverse Cardiac Events (MACE) [ Time Frame: From randomization until the adjudication cut-off date of May 31 2013 (maximum time on study was 41 months). ] [ Designated as safety issue: No ]
    Primary Major Adverse Cardiac Events were defined as a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke; these events were adjudicated by an independent cardiovascular endpoints committee.

Secondary Outcome Measures:
  • Percentage of Participants With Secondary Major Adverse Cardiac Events (MACE) [ Time Frame: From randomization until the adjudication cut-of date of May 31 2013 (maximum time on study was 41 months). ] [ Designated as safety issue: No ]
    Secondary MACE composite consisted of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or urgent revascularization due to unstable angina; these events were adjudicated by an independent cardiovascular endpoint committee.

Enrollment: 5380
Study Start Date: September 2009
Study Completion Date: June 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Placebo
Alogliptin placebo matching tablets, orally, once daily. Participants continued to receive standard of care for cardiovascular disease and diabetes according to regional guidelines.
Drug: Placebo
Alogliptin placebo matching tablets
Experimental: Alogliptin
Alogliptin 25 mg, tablets, orally, once daily for participants with normal or mildly impaired renal function as defined by estimated glomerular filtration rate (eGFR) ≥ 60 mL/min). Alogliptin 12.5 mg, tablets, orally, once daily for participants with moderately impaired renal function (eGFR ≥30 and <60 mL/min). Alogliptin 6.25 mg, tablets, orally, once daily for participants with severely impaired renal function or end stage renal disease (eGFR <30 mL/min). Participants continued to receive standard of care for cardiovascular disease and diabetes according to regional guidelines.
Drug: Alogliptin
Alogliptin tablets
Other Names:
  • Nesina®
  • SYR-322
  • SYR110322

Detailed Description:

Alogliptin is a selective and potent dipeptidyl peptidase-4 inhibitor developed by Takeda for use in patients with type 2 diabetes mellitus.

Cardiovascular outcomes is of special interest in the type 2 diabetes mellitus population, particularly in type 2 diabetes mellitus patients who have cardiovascular disease and are at high risk for major adverse cardiac events, such as those patients who have had recent acute coronary syndrome.

This study has been designed to evaluate the cardiovascular safety of alogliptin versus placebo in addition to Standard of Care in adults with type 2 diabetes mellitus and acute coronary syndrome.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of type 2 diabetes mellitus
  • Is receiving monotherapy or combination antidiabetic therapy with a glycosylated hemoglobin level between 6.5% and 11.0%, inclusive, at Screening (between 7.0 and 11.0%, inclusive, if the participant's antidiabetic regimen includes insulin)
  • Diagnosis of acute coronary syndrome within 15 to 90 days prior to randomization.

Exclusion Criteria:

  • Signs of type 1 diabetes mellitus
  • Currently receiving a glucagon-like peptide-1 analogue for glycemic control of type 2 diabetes mellitus at Screening
  • Received a dipeptidyl peptidase-4 inhibitor for either more than 14 days total or within the 3 months prior to Screening.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00968708

  Show 918 Study Locations
Sponsors and Collaborators
Study Director: Medical Director Clinical Science Takeda
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Takeda Identifier: NCT00968708     History of Changes
Other Study ID Numbers: SYR-322_402  U1111-1111-6825  2009-011222-34  JapicCTI-101246  DOH-27-0310-3047  09/H0709/63  CTRI/2010/091/000046  2009-011222-34  2009-011222-34  NMRR-09-872-4471 
Study First Received: August 28, 2009
Results First Received: March 8, 2014
Last Updated: April 15, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Argentina: Human Research Bioethics Committee
Austria: Agency for Health and Food Safety
Austria: Ethikkommission
Austria: Federal Ministry for Health and Women
Austria: Federal Office for Safety in Health Care
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Australia: National Health and Medical Research Council
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Institutional Review Board
Belgium: Ministry of Social Affairs, Public Health and the Environment
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Brazil: Ministry of Health
Brazil: National Committee of Ethics in Research
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Bulgaria: Ministry of Health
Canada: Canadian Institutes of Health Research
Canada: Ethics Review Committee
Canada: Health Canada
Canada: Ministry of Health & Long Term Care, Ontario
Chile: Comisión Nacional de Investigación Científica y Tecnológica
Chile: Instituto de Salud Pública de Chile
Costa Rica: Ministry of Health Costa Rica
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
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Denmark: Danish Medicines Agency
Denmark: Ethics Committee
Denmark: National Board of Health
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Denmark: Ministry of Health
Denmark: The Regional Committee on Biomedical Research Ethics
European Union: European Medicines Agency
Finland: Ethics Committee
Finland: Ministry of Social Affairs and Health
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Direction Générale de la Santé
France: French Data Protection Authority
France: Institutional Ethical Committee
France: Ministry of Health
France: National Consultative Ethics Committee for Health and Life Sciences
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Germany: Federal Ministry of Education and Research
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Hungary: National Institute of Pharmacy
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India: Ministry of Health
India: Ministry of Science and Technology
India: Science and Engineering Research Council
Israel: The Israel National Institute for Health Policy Research and Health Services Research
Israel: Ethics Commission
Israel: Israeli Health Ministry Pharmaceutical Administration
Israel: Ministry of Health
Italy: Ethics Committee
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Institute of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency
Korea: Food and Drug Administration
Latvia: State Agency of Medicines
Lithuania: Bioethics Committee
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Malaysia: Ministry of Health
Mexico: Ethics Committee
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Mexico: Federal Commission for Sanitary Risks Protection
Mexico: Ministry of Health
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Netherlands: Dutch Health Care Inspectorate
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: Medicines Evaluation Board (MEB)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
New Zealand: Food Safety Authority
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New Zealand: Health and Disability Ethics Committees
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New Zealand: Medsafe
Peru: Ethics Committee
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Peru: Ministry of Health
Philippines: Department of Health
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Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: Ministry of Health
Poland: Ministry of Science and Higher Education
Portugal: Ethics Committee for Clinical Research
Portugal: Health Ethic Committee
Portugal: National Pharmacy and Medicines Institute
Romania: Ministry of Public Health
Romania: National Medicines Agency
Romania: State Institute for Drug Control
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Russia: Pharmacological Committee, Ministry of Health
Serbia: Ethics Committee
Slovakia: State Institute for Drug Control
South Africa: Department of Health
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South Africa: National Health Research Ethics Council
South Korea: Institutional Review Board
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Comité Ético de Investigación Clínica
Spain: Ethics Committee
Spain: Ministry of Health
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Sweden: Institutional Review Board
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Sweden: Regional Ethical Review Board
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Thailand: Ethical Committee
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Turkey: Ethics Committee
Turkey: Ministry of Health
Ukraine: Ministry of Health
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United Kingdom: Research Ethics Committee
United States: Federal Government
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Keywords provided by Takeda:
Diabetes Mellitus - Type 2
Diabetes Mellitus
cardiovascular outcomes
heart attack
dipeptidyl-peptidase IV inhibitors
metabolic disorders
metabolic diseases
glucose metabolism disorders

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Acute Coronary Syndrome
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on January 17, 2017