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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.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00968708
First Posted: August 31, 2009
Last Update Posted: May 2, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Takeda
Results First Submitted: March 8, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Diabetes Mellitus, Type 2
Acute Coronary Syndrome
Interventions: Drug: Alogliptin
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants took part in the study at 898 investigative sites worldwide from 24 September 2009 to 18 June 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with a diagnosis of type 2 diabetes mellitus and acute coronary syndrome were enrolled equally in 1 of 2 treatment groups, once a day placebo or alogliptin, in addition to receiving standard of care for cardiovascular disease and diabetes.

Reporting Groups
  Description
Placebo Alogliptin placebo matching tablets, orally, once daily. Participants continued to receive standard of care for cardiovascular disease and diabetes according to regional guidelines.
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.

Participant Flow:   Overall Study
    Placebo   Alogliptin
STARTED   2679   2701 
Treated   2676   2698 
COMPLETED   2361   2403 
NOT COMPLETED   318   298 
Adverse Event                169                150 
Major Protocol Deviation                0                1 
Lost to Follow-up                19                11 
Voluntary Withdrawal                104                101 
Investigator Discretion                0                1 
Other                26                34 



  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
  Description
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 
Age 
[Units: Years]
Mean (Standard Deviation)
 60.7  (9.88)   61.0  (9.96)   60.9  (9.92) 
Gender 
[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). ]
  Hide Outcome Measure 2

Measure Type Secondary
Measure Title Percentage of Participants With Secondary Major Adverse Cardiac Events (MACE)
Measure Description 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.
Time Frame From randomization until the adjudication cut-of date of May 31 2013 (maximum time on study was 41 months).  

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

Reporting Groups
  Description
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).

Measured Values
   Placebo   Alogliptin 
Participants Analyzed 
[Units: Participants]
 2679   2701 
Percentage of Participants With Secondary Major Adverse Cardiac Events (MACE) 
[Units: Percentage of participants]
 13.4   12.7 


Statistical Analysis 1 for Percentage of Participants With Secondary Major Adverse Cardiac Events (MACE)
Groups [1] All groups
Statistical Test Type [2] Non-Inferiority or Equivalence
Hazard Ratio (HR) [3] 0.952
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  If the upper bound of the confidence interval for the primary MACE composite was <1.0, then statistical superiority of alogliptin to placebo for the secondary MACE composite would be demonstrated.
[3] Other relevant estimation information:
  No text entered.




  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
No text entered.


  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
e-mail: clinicaltrialregistry@tpna.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Takeda
ClinicalTrials.gov 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 )
First Submitted: August 28, 2009
First Posted: August 31, 2009
Results First Submitted: March 8, 2014
Results First Posted: April 15, 2014
Last Update Posted: May 2, 2014