Efficacy and Safety of Alogliptin Plus Metformin Compared to Glipizide Plus Metformin in Patients With Type 2 Diabetes Mellitus (ENDURE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00856284
First received: March 4, 2009
Last updated: September 25, 2013
Last verified: September 2013
Results First Received: September 25, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: Alogliptin
Drug: Metformin
Drug: Glipizide

  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 310 study sites worldwide from 05 March 2009 to 17 October 2012.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with type 2 diabetes mellitus experiencing inadequate glycemic control while on metformin therapy were enrolled equally in 1 of 3 treatment groups: alogliptin 12.5 mg once daily (QD), alogliptin 25 mg QD, and glipizide 5 mg QD.

Reporting Groups
  Description
Metformin + Alogliptin 12.5 mg Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Alogliptin 25 mg Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Glipizide Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Participant Flow:   Overall Study
    Metformin + Alogliptin 12.5 mg     Metformin + Alogliptin 25 mg     Metformin + Glipizide  
STARTED     880     885     874  
Received Study Drug     873     878     869  
COMPLETED     472     493     427  
NOT COMPLETED     408     392     447  
Hyperglycemic rescue                 231                 201                 235  
Adverse Event                 60                 74                 82  
Major protocol deviation                 24                 16                 15  
Lost to Follow-up                 20                 22                 28  
Voluntary withdrawal                 48                 52                 62  
Pregnancy                 1                 2                 0  
Investigator discretion                 9                 8                 10  
Other                 15                 17                 14  
Randomized in error                 0                 0                 1  



  Baseline Characteristics
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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.
The Randomized Set included all enrolled subjects who were subsequently randomized.

Reporting Groups
  Description
Metformin + Alogliptin 12.5 mg Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Alogliptin 25 mg Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Glipizide Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.
Total Total of all reporting groups

Baseline Measures
    Metformin + Alogliptin 12.5 mg     Metformin + Alogliptin 25 mg     Metformin + Glipizide     Total  
Number of Participants  
[units: participants]
  880     885     874     2639  
Age  
[units: years]
Mean ± Standard Deviation
  55.2  ± 9.60     55.5  ± 9.81     55.4  ± 9.60     55.4  ± 9.67  
Age, Customized [1]
[units: participants]
       
<65 years     734     710     723     2167  
≥65 years     146     175     151     472  
≥75 years     13     17     15     45  
Gender  
[units: participants]
       
Female     461     433     433     1327  
Male     419     452     441     1312  
Race/Ethnicity, Customized  
[units: participants]
       
American Indian or Alaska Native     40     42     36     118  
Asian     191     207     203     601  
Black or African American     74     66     81     221  
Native Hawaiian or Other Pacific Islander     7     1     4     12  
White     557     555     533     1645  
Multiracial     11     14     17     42  
Race/Ethnicity, Customized  
[units: participants]
       
Hispanic or Latino     192     204     192     588  
Not Hispanic or Latino     688     681     682     2051  
Body Mass Index (BMI) [2]
[units: kg/m^2]
Mean ± Standard Deviation
  31.27  ± 5.417     31.27  ± 5.341     31.11  ± 5.320     31.22  ± 5.358  
Glycosylated hemoglobin (HbA1c) [3]
[units: percentage]
Mean ± Standard Deviation
  7.59  ± 0.599     7.61  ± 0.606     7.60  ± 0.617     7.60  ± 0.607  
Baseline HbA1c Category  
[units: participants]
       
<8.0%     615     620     613     1848  
≥8.0%     265     265     261     791  
Diabetes duration [4]
[units: years]
Mean ± Standard Deviation
  5.65  ± 5.324     5.42  ± 4.730     5.48  ± 4.884     5.52  ± 4.985  
Metformin dose  
[units: mg]
Mean ± Standard Deviation
  1825.2  ± 405.59     1837.2  ± 373.06     1823.4  ± 390.63     1828.6  ± 389.85  
Glomerular filtration rate [5]
[units: mL/min/1.73m^2]
Mean ± Standard Deviation
       
MDRD     83.04  ± 16.586     82.35  ± 16.199     82.28  ± 16.994     82.56  ± 16.591  
Cockcroft-Gault     109.3  ± 33.40     109.3  ± 32.85     108.0  ± 32.64     108.9  ± 32.96  
Smoking history  
[units: participants]
       
Never smoked     543     586     578     1707  
Current smoker     135     122     111     368  
Ex-smoker     202     177     185     564  
[1] Categories ≥65 years and ≥75 years are not mutually exclusive. Participants ≥75 years are counted in both categories.
[2] BMI data available for 879, 885 and 872 participants in each treatment arm, respectively.
[3] Mean HbA1c data includes 877, 883 and 870 participants in each treatment arm, respectively.
[4] Diabetes duration data available for 880, 884 and 874 participants in each treatment arm, respectively.
[5] Glomerular filtration rate (GFR) was calculated using the modification of diet in renal disease (MDRD) formula and the Cockcroft-Gault formula. Data include 877, 883 and 870 participants in each treatment arm, respectively.



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52   [ Time Frame: Baseline and Week 52 ]

Measure Type Primary
Measure Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52
Measure Description The change from Baseline to Week 52 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The least squares (LS) means are from an analysis of covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.
Time Frame Baseline and Week 52  
Safety Issue No  

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.
The Per-protocol set included all randomized patients who took at least 1 dose of double-blind study drug, with a Baseline assessment and at least 1 post-baseline assessment for that variable and who had no major protocol violations. Last observation carried forward (LOCF) was used.

Reporting Groups
  Description
Metformin + Alogliptin 12.5 mg Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Alogliptin 25 mg Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Glipizide Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Measured Values
    Metformin + Alogliptin 12.5 mg     Metformin + Alogliptin 25 mg     Metformin + Glipizide  
Number of Participants Analyzed  
[units: participants]
  371     382     336  
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52  
[units: percentage glycosylated hemoglobin]
Least Squares Mean ± Standard Error
  -0.81  ± 0.027     -0.76  ± 0.027     -0.73  ± 0.029  


Statistical Analysis 1 for Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52
Groups [1] Metformin + Alogliptin 25 mg vs. Metformin + Glipizide
Non-Inferiority/Equivalence Test [2] Yes
LS Mean Difference [3] -0.03
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The null hypotheses were tested in a fixed order at the 1-sided 0.0125 significance level at Weeks 52 and 104, independently: H01: Alogliptin 25 mg was inferior in HbA1c change from Baseline vs glipizide. H02: Alogliptin 12.5 mg was inferior vs glipizide. H03: Alogliptin 25 mg was not superior vs glipizide. H04: Alogliptin 12.5 mg was not superior vs glipizide. Each subsequent null hypothesis was tested only if all previously tested null hypotheses were rejected with respect to Weeks 52 and 104.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 25 mg and glipizide in HbA1c change from Baseline was less than 0.3%. If the null hypothesis H01 was rejected, then H02 was tested to show noninferiority of alogliptin 12.5 mg versus glipizide with a margin of 0.3%. Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 12.5 mg and glipizide in HbA1c change from Baseline was less than 0.3%.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52
Groups [1] Metformin + Alogliptin 12.5 mg vs. Metformin + Glipizide
Non-Inferiority/Equivalence Test [2] Yes
LS Mean Difference [3] -0.09
[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:
  Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 25 mg and glipizide in HbA1c change from Baseline was less than 0.3%. If the null hypothesis H01 was rejected, then H02 was tested to show noninferiority of alogliptin 12.5 mg versus glipizide with a margin of 0.3%. Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 12.5 mg and glipizide in HbA1c change from Baseline was less than 0.3%.
[3] Other relevant estimation information:
  No text entered.



2.  Primary:   Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 104   [ Time Frame: Baseline and Week 104 ]

Measure Type Primary
Measure Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 104
Measure Description The change from Baseline to Week 104 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The least squares (LS) means are from an analysis of covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.
Time Frame Baseline and Week 104  
Safety Issue No  

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.
The Per-protocol set included all randomized patients who took at least 1 dose of double-blind study drug, with a Baseline assessment and at least 1 post-baseline assessment for that variable and who had no major protocol violations. Last observation carried forward was used (LOCF).

Reporting Groups
  Description
Metformin + Alogliptin 12.5 mg Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Alogliptin 25 mg Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Glipizide Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Measured Values
    Metformin + Alogliptin 12.5 mg     Metformin + Alogliptin 25 mg     Metformin + Glipizide  
Number of Participants Analyzed  
[units: participants]
  371     382     336  
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 104  
[units: percentage glycosylated hemoglobin]
Least Squares Mean ± Standard Error
  -0.68  ± 0.037     -0.72  ± 0.037     -0.59  ± 0.039  


Statistical Analysis 1 for Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 104
Groups [1] Metformin + Alogliptin 25 mg vs. Metformin + Glipizide
Non-Inferiority/Equivalence Test [2] Yes
LS Mean Difference [3] -0.13
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The null hypotheses were tested in a fixed order at the 1-sided 0.0125 significance level at Weeks 52 and 104, independently: H01: Alogliptin 25 mg was inferior in HbA1c change from Baseline vs glipizide. H02: Alogliptin 12.5 mg was inferior vs glipizide. H03: Alogliptin 25 mg was not superior vs glipizide. H04: Alogliptin 12.5 mg was not superior vs glipizide. Each subsequent null hypothesis was tested only if all previously tested null hypotheses were rejected with respect to Weeks 52 and 104.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 25 mg and glipizide in HbA1c change from Baseline was less than 0.3%. If the null hypothesis H01 was rejected, then H02 was tested to show noninferiority of alogliptin 12.5 mg versus glipizide with a margin of 0.3%. Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 12.5 mg and glipizide in HbA1c change from Baseline was less than 0.3%.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 104
Groups [1] Metformin + Alogliptin 12.5 mg vs. Metformin + Glipizide
Non-Inferiority/Equivalence Test [2] Yes
LS Mean Difference [3] -0.09
[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:
  Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 25 mg and glipizide in HbA1c change from Baseline was less than 0.3%. If the null hypothesis H01 was rejected, then H02 was tested to show noninferiority of alogliptin 12.5 mg versus glipizide with a margin of 0.3%. Non-inferiority was met if the upper limit of the 1-sided 98.75% CI for the difference between alogliptin 12.5 mg and glipizide in HbA1c change from Baseline was less than 0.3%.
[3] Other relevant estimation information:
  No text entered.



3.  Secondary:   Change From Baseline in Glycosylated Hemoglobin at Other Time Points   [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 39, 65, 78, and 91. ]

Measure Type Secondary
Measure Title Change From Baseline in Glycosylated Hemoglobin at Other Time Points
Measure Description The change from Baseline over time in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). LS means are from an ANCOVA model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.
Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 26, 39, 65, 78, and 91.  
Safety Issue No  

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.
Per-protocol set; LOCF was used.

Reporting Groups
  Description
Metformin + Alogliptin 12.5 mg Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Alogliptin 25 mg Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Glipizide Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Measured Values
    Metformin + Alogliptin 12.5 mg     Metformin + Alogliptin 25 mg     Metformin + Glipizide  
Number of Participants Analyzed  
[units: participants]
  371     382     336  
Change From Baseline in Glycosylated Hemoglobin at Other Time Points  
[units: percentage of glycosylated hemoglobin]
Least Squares Mean ± Standard Error
     
Week 4 (n=341, 354, 318)     -0.37  ± 0.020     -0.40  ± 0.020     -0.41  ± 0.021  
Week 8 (n=370, 382, 336)     -0.56  ± 0.024     -0.60  ± 0.024     -0.66  ± 0.025  
Week 12 (n=371, 382, 336)     -0.69  ± 0.025     -0.71  ± 0.025     -0.78  ± 0.026  
Week 16 (n=371, 382, 336)     -0.74  ± 0.026     -0.76  ± 0.025     -0.78  ± 0.027  
Week 20 (n=371, 382, 336)     -0.76  ± 0.026     -0.78  ± 0.025     -0.79  ± 0.027  
Week 26 (n=371, 382, 336)     -0.80  ± 0.027     -0.79  ± 0.026     -0.80  ± 0.028  
Week 39 (n=371, 382, 336)     -0.81  ± 0.026     -0.81  ± 0.025     -0.74  ± 0.027  
Week 65 (n=371, 382, 336)     -0.81  ± 0.029     -0.83  ± 0.028     -0.76  ± 0.030  
Week 78 (n=371, 382, 336)     -0.82  ± 0.030     -0.80  ± 0.030     -0.73  ± 0.032  
Week 91 (n=371, 382, 336)     -0.76  ± 0.033     -0.77  ± 0.033     -0.68  ± 0.035  

No statistical analysis provided for Change From Baseline in Glycosylated Hemoglobin at Other Time Points



4.  Secondary:   Change From Baseline in Fasting Plasma Glucose Over Time   [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 26, 39, 52, 65, 78, 91, and 104. ]

Measure Type Secondary
Measure Title Change From Baseline in Fasting Plasma Glucose Over Time
Measure Description The change from Baseline in fasting plasma glucose (FPG) was assessed at Weeks 2, 4, 8, 12, 16, 20, 26, 39, 52, 65, 78, 91, and 104. LS means are from an ANCOVA model with treatment, study schedule, and geographic region as class variables, and Baseline FPG and Baseline metformin dose as covariates.
Time Frame Baseline and Weeks 2, 4, 8, 12, 16, 20, 26, 39, 52, 65, 78, 91, and 104.  
Safety Issue No  

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, which included all randomized patients who received at least 1 dose of double-blind study drug who had a Baseline assessment and at least 1 post-baseline assessment for FPG. LOCF was used.

Reporting Groups
  Description
Metformin + Alogliptin 12.5 mg Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Alogliptin 25 mg Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Glipizide Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Measured Values
    Metformin + Alogliptin 12.5 mg     Metformin + Alogliptin 25 mg     Metformin + Glipizide  
Number of Participants Analyzed  
[units: participants]
  867     867     859  
Change From Baseline in Fasting Plasma Glucose Over Time  
[units: mg/dL]
Least Squares Mean ± Standard Error
     
Week 2 (n=781, 803, 777)     -10.2  ± 0.89     -11.4  ± 0.87     -7.7  ± 0.89  
Week 4 (n=863, 865, 855)     -10.6  ± 0.85     -11.6  ± 0.85     -10.2  ± 0.85  
Week 8 (n=867, 867, 859)     -9.2  ± 0.91     -11.6  ± 0.91     -9.3  ± 0.92  
Week 12 (n=867, 867, 859)     -10.7  ± 0.94     -11.2  ± 0.94     -9.4  ± 0.95  
Week 16 (n=867, 867, 859)     -8.6  ± 0.98     -9.9  ± 0.98     -7.1  ± 0.98  
Week 20 (n=867, 867, 859)     -7.6  ± 1.02     -10.1  ± 1.02     -5.5  ± 1.02  
Week 26 (n=867, 867, 859)     -7.5  ± 1.06     -10.1  ± 1.06     -4.3  ± 1.06  
Week 39 (n=867, 867, 859)     -6.9  ± 1.14     -8.4  ± 1.14     -0.6  ± 1.15  
Week 52 (n=867, 867, 859)     -5.0  ± 1.22     -7.0  ± 1.22     0.9  ± 1.23  
Week 65 (n=867, 867, 859)     -3.4  ± 1.21     -5.9  ± 1.21     1.4  ± 1.21  
Week 78 (n=867, 867, 859)     -2.8  ± 1.47     -5.1  ± 1.47     5.1  ± 1.48  
Week 91 (n=867, 867, 859)     -0.9  ± 1.27     -3.4  ± 1.27     4.9  ± 1.28  
Week 104 (n=867, 867, 859)     -0.9  ± 1.28     -3.2  ± 1.28     5.4  ± 1.29  

No statistical analysis provided for Change From Baseline in Fasting Plasma Glucose Over Time



5.  Secondary:   Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5%   [ Time Frame: Weeks 26, 52, 78, and 104. ]

Measure Type Secondary
Measure Title Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5%
Measure Description The percentage of participants with HbA1c less than or equal to 6.5% at Weeks 26, 52, 78, and 104. Participants who did not complete the scheduled Week 104 visit were assessed based on their response at the time of discontinuation.
Time Frame Weeks 26, 52, 78, and 104.  
Safety Issue No  

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. Participants who did not complete the scheduled Week 26, Week 52, Week 78 or Week 104 visit were assessed based on their response at the time of discontinuation.

Reporting Groups
  Description
Metformin + Alogliptin 12.5 mg Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Alogliptin 25 mg Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Glipizide Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Measured Values
    Metformin + Alogliptin 12.5 mg     Metformin + Alogliptin 25 mg     Metformin + Glipizide  
Number of Participants Analyzed  
[units: participants]
  873     878     869  
Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5%  
[units: percentage of participants]
     
Week 26     25.6     26.2     24.8  
Week 52     24.5     24.8     20.8  
Week 78     24.2     26.4     21.8  
Week 104     23.5     24.1     19.0  

No statistical analysis provided for Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5%



6.  Secondary:   Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0%   [ Time Frame: Weeks 26, 52, 78, and 104. ]

Measure Type Secondary
Measure Title Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0%
Measure Description Percentage of participants with HbA1c ≤ 7.0% at Weeks 26, 52, 78, and 104. Participants who did not complete the scheduled Week 104 visit were assessed based on their response at the time of discontinuation.
Time Frame Weeks 26, 52, 78, and 104.  
Safety Issue No  

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. Participants who did not complete the scheduled Week 26, Week 52, Week 78 or Week 104 visit were assessed based on their response at the time of discontinuation.

Reporting Groups
  Description
Metformin + Alogliptin 12.5 mg Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Alogliptin 25 mg Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Glipizide Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Measured Values
    Metformin + Alogliptin 12.5 mg     Metformin + Alogliptin 25 mg     Metformin + Glipizide  
Number of Participants Analyzed  
[units: participants]
  873     878     869  
Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0%  
[units: percentage of participants]
     
Week 26     56.4     59.2     56.1  
Week 52     51.7     55.5     47.4  
Week 78     48.8     52.4     46.6  
Week 104     45.6     48.5     42.8  

No statistical analysis provided for Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0%



7.  Secondary:   Change From Baseline in Body Weight Over Time   [ Time Frame: Baseline and Weeks 12, 26, 39, 52, 65, 78, 91, and 104. ]

Measure Type Secondary
Measure Title Change From Baseline in Body Weight Over Time
Measure Description LS Means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and Baseline weight and Baseline metformin dose as covariates.
Time Frame Baseline and Weeks 12, 26, 39, 52, 65, 78, 91, and 104.  
Safety Issue No  

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, LOCF was used.

Reporting Groups
  Description
Metformin + Alogliptin 12.5 mg Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Alogliptin 25 mg Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
Metformin + Glipizide Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Measured Values
    Metformin + Alogliptin 12.5 mg     Metformin + Alogliptin 25 mg     Metformin + Glipizide  
Number of Participants Analyzed  
[units: participants]
  867     868     861  
Change From Baseline in Body Weight Over Time  
[units: kg]
Least Squares Mean ± Standard Error
     
Week 12     -0.51  ± 0.076     -0.53  ± 0.076     0.71  ± 0.077  
Week 26     -0.65  ± 0.101     -0.71  ± 0.101     0.86  ± 0.101  
Week 39     -0.60  ± 0.109     -0.86  ± 0.109     0.97  ± 0.110  
Week 52     -0.63  ± 0.117     -0.90  ± 0.117     0.89  ± 0.117  
Week 65     -0.70  ± 0.122     -0.92  ± 0.122     0.87  ± 0.123  
Week 78     -0.78  ± 0.124     -0.94  ± 0.124     0.88  ± 0.125  
Week 91     -0.67  ± 0.127     -0.88  ± 0.127     0.89  ± 0.127  
Week 104     -0.68  ± 0.127     -0.89  ± 0.127     0.95  ± 0.127  

No statistical analysis provided for Change From Baseline in Body Weight Over Time




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
The Week 52 results summarized in herein differ from the Week 52 results summarized in an interim analysis, because the per protocol set (PPS) defined for the final analysis included fewer subjects than the PPS defined for the interim analysis.


  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, Clinical Science
Organization: Takeda
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com


No publications provided


Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00856284     History of Changes
Other Study ID Numbers: SYR-322_305, 2008-007444-34, U1111-1111-7397, HKCTR-862, DOH-27-0709-2825, 09/H0703/66, NMRR-09-203-3590
Study First Received: March 4, 2009
Results First Received: September 25, 2013
Last Updated: September 25, 2013
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