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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
Results First Received: March 8, 2014  
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
Conditions: Diabetes Mellitus, Type 2
Acute Coronary Syndrome
Interventions: Drug: Alogliptin
Drug: Placebo

  Participant Flow

  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS) - all randomized participants who signed informed consent.

Reporting Groups
Placebo Alogliptin placebo matching tablets, orally, once daily.
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).
Total Total of all reporting groups

Baseline Measures
   Placebo   Alogliptin   Total 
Overall Participants Analyzed 
[Units: Participants]
 2679   2701   5380 
[Units: Years]
Mean (Standard Deviation)
 60.7  (9.88)   61.0  (9.96)   60.9  (9.92) 
[Units: Participants]
Female   856   873   1729 
Male   1823   1828   3651 
Race/Ethnicity, Customized 
[Units: Participants]
American Indian or Alaska Native   54   56   110 
Asian   542   547   1089 
Black or African American   115   101   216 
Native Hawaiian or Other Pacific Islander   5   6   11 
White   1943   1966   3909 
More than one race   20   25   45 
Race/Ethnicity, Customized 
[Units: Participants]
Hispanic or Latino   764   773   1537 
Non-Hispanic or Latino   1915   1928   3843 
Region of Enrollment 
[Units: Participants]
Argentina   136   136   272 
Australia   7   8   15 
Austria   8   8   16 
Belgium   11   12   23 
Brazil   179   181   360 
Bulgaria   41   41   82 
Canada   54   55   109 
Chile   51   55   106 
Colombia   15   13   28 
Croatia   38   39   77 
Czech Republic   13   13   26 
Denmark   3   3   6 
Egypt   7   7   14 
Finland   12   10   22 
France   11   11   22 
Germany   26   27   53 
Greece   0   1   1 
Guatemala   25   24   49 
Hong Kong   11   12   23 
Hungary   60   59   119 
India   165   165   330 
Israel   100   101   201 
Italy   25   25   50 
Japan   105   104   209 
Kuwait   2   3   5 
Latvia   6   6   12 
Lithuania   16   20   36 
Malaysia   39   42   81 
Mexico   192   191   383 
New Zealand   13   13   26 
Peru   79   81   160 
Philippines   52   50   102 
Poland   121   118   239 
Portugal   13   16   29 
Puerto Rico   16   19   35 
Korea, Republic Of   61   62   123 
Romania   40   38   78 
Russian Federation   153   151   304 
Serbia   35   35   70 
Slovakia   46   49   95 
South Africa   39   41   80 
Spain   21   22   43 
Sweden   16   16   32 
Taiwan, Province Of China   14   13   27 
Thailand   57   58   115 
Ukraine   138   138   276 
United Arab Emirates   3   3   6 
United Kingdom   32   34   66 
United States   372   372   744 
Body Mass Index 
[Units: Kg/m^2]
Mean (Standard Deviation)
 29.53  (5.758)   29.42  (5.422)   29.48  (5.591) 
Duration of Type 2 Diabetes Mellitus 
[Units: Years]
Mean (Standard Deviation)
 9.18  (8.121)   9.13  (8.198)   9.16  (8.159) 
Smoking History 
[Units: Participants]
Never smoked   1144   1158   2302 
Current smoker   383   351   734 
Ex-smoker   1152   1192   2344 
Estimated Glomerular Filtration Rate (eGFR) [1] 
[Units: mL/min/1.73 m^2]
Mean (Standard Deviation)
 71.01  (21.541)   70.86  (21.297)   70.93  (21.417) 
[1] Calculated using the Modification of Diet in Renal Disease (MDRD) formula
Renal Impairment Category [1] 
[Units: Participants]
Normal Renal Function   440   399   839 
Mild Renal Impairment   1446   1530   2976 
Moderate Renal Impairment   714   694   1408 
Severe Renal Impairment/End-Stage Renal Disease   79   78   157 
[1] Normal renal function: eGFR ≥90 mL/min/1.73 m^2; Mild renal impairment: eGFR ≥60 and <90 mL/min/1.73 m^2; Moderate renal impairment: eGFR ≥30 and <60 mL/min/1.73 m^2; Severe renal impairment: eGFR <30 mL/min/1.73 m^2; End-stage renal disease (ESRD): eGFR <15 mL/min/1.73 m^2
Index Acute Coronary Syndrome (ACS) Event Type [1] 
[Units: Participants]
Myocardial Infarction   2068   2084   4152 
Unstable Angina   605   609   1214 
[1] Six participants in the placebo arm and 7 participants in the alogliptin arm are not included because they did not meet the ACS requirements for study inclusion.
Time From Index ACS Event to Randomization [1] 
[Units: Days]
Mean (Standard Deviation)
 48.0  (21.95)   47.6  (22.04)   47.8  (22.00) 
[1] Six participants in the placebo arm and 7 participants in the alogliptin arm are not included because they did not meet the ACS requirements for study inclusion.

  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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). ]

2.  Secondary:   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). ]

  Serious Adverse Events

  Other Adverse Events

  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact:  
Name/Title: Medical Director
Organization: Takeda
phone: 800-778-2860

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 ( Registry Identifier: WHO )
2009-011222-34 ( Registry Identifier: EudraCT )
JapicCTI-101246 ( Registry Identifier: JapicCTI )
DOH-27-0310-3047 ( Registry Identifier: SANCTR )
09/H0709/63 ( Registry Identifier: NRES )
CTRI/2010/091/000046 ( Registry Identifier: CTRI )
2009-011222-34 ( Registry Identifier: REPEC )
2009-011222-34 ( Registry Identifier: OsSC )
NMRR-09-872-4471 ( Registry Identifier: NMRR )
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
Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: Ethics Committee
Denmark: National Board of Health
Denmark: The Danish National Committee on Biomedical Research Ethics
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
Germany: Federal Ministry of Food, Agriculture and Consumer Protection
Germany: German Institute of Medical Documentation and Information
Germany: Ministry of Health
Germany: Paul-Ehrlich-Institut
Guatemala: Ministry of Public Health and Social Assistance
Hong Kong: Department of Health
Hong Kong: Ethics Committee
Hong Kong: Joint CUHK-NTEC Clinical Research Ethics Committee
Hungary: National Institute of Pharmacy
India: Central Drugs Standard Control Organization
India: Department of Atomic Energy
India: Drugs Controller General of India
India: Indian Council of Medical Research
India: Institutional Review Board
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
Lithuania: State Medicine Control Agency - Ministry of Health
Malaysia: Ministry of Health
Mexico: Ethics Committee
Mexico: Federal Commission for Protection Against Health Risks
Mexico: Federal Commission for Sanitary Risks Protection
Mexico: Ministry of Health
Mexico: National Council of Science and Technology
Mexico: National Institute of Public Health, Health Secretariat
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
New Zealand: Health Research Council
New Zealand: Health and Disability Ethics Committees
New Zealand: Institutional Review Board
New Zealand: Medsafe
Peru: Ethics Committee
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Peru: Ministry of Health
Philippines: Department of Health
Philippines: Bureau of Food and Drugs
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
South Africa: Medicines Control Council
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
Spain: Ministry of Health and Consumption
Spain: Spanish Agency of Medicines
Sweden: Institutional Review Board
Sweden: Medical Products Agency
Sweden: Regional Ethical Review Board
Sweden: Swedish National Council on Medical Ethics
Sweden: Swedish Research Council
Sweden: The National Board of Health and Welfare
Thailand: Ethical Committee
Thailand: Food and Drug Administration
Thailand: Khon Kaen University Ethics Committee for Human Research
Thailand: Ministry of Public Health
Turkey: Ethics Committee
Turkey: Ministry of Health
Ukraine: Ministry of Health
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Department of Health
United Kingdom: Food Standards Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee
United States: Federal Government
United States: Institutional Review Board