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Efficacy and Safety Study of Alogliptin and Insulin in the Treatment of Type 2 Diabetes.

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.
ClinicalTrials.gov Identifier: NCT00286429
Recruitment Status : Completed
First Posted : February 3, 2006
Results First Posted : August 12, 2011
Last Update Posted : February 3, 2012
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Diabetes Mellitus
Interventions Drug: Alogliptin and insulin
Drug: Insulin
Enrollment 390
Recruitment Details Participants enrolled at 110 investigative sites in Australia, Brazil, Chile, Guatemala, Germany, Hungary, India, Mexico, New Zealand, the Netherlands, Poland, South Africa, and the United States from 16 March 2006 to 18 September 2006
Pre-assignment Details Participants with a historical diagnosis of type 2 diabetes mellitus who were inadequately controlled while being treated with insulin with or without metformin were enrolled in one of three, once-daily (QD) treatment groups.
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Period Title: Overall Study
Started 130 131 129
Completed 55 83 77
Not Completed 75 48 52
Reason Not Completed
Adverse Event             4             1             6
Lack of Efficacy             52             27             25
Lost to Follow-up             2             4             3
Physician Decision             10             7             7
Protocol Violation             3             5             4
Withdrawal by Subject             3             2             6
Administrative Error             1             1             1
Administrative Decision             0             1             0
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD Total
Hide Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks. Total of all reporting groups
Overall Number of Baseline Participants 130 131 129 390
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 130 participants 131 participants 129 participants 390 participants
<65 years 109 112 106 327
≥65 years 21 19 23 63
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 130 participants 131 participants 129 participants 390 participants
Female
68
  52.3%
76
  58.0%
85
  65.9%
229
  58.7%
Male
62
  47.7%
55
  42.0%
44
  34.1%
161
  41.3%
1.Primary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26.
Hide Description The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 26 or final visit and glycosylated hemoglobin collected at baseline.
Time Frame Baseline and Week 26.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF). ANCOVA = Analysis of covariance.
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 126 130 126
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.13  (0.077) -0.63  (0.076) -0.71  (0.078)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 26. For comparison of either alogliptin dose vs. placebo (2-sample t test), study sample size >=390 participants had 95% power to detect a treatment difference as small as 0.4% in the per protocol analysis set assuming a standard deviation of 0.8%, a 2-sided test at 0.05 significance level and >=80% of subjects meeting the per protocol criteria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments A step-down strategy was used for the primary analysis. First, the 25mg dose was compared to placebo at the 2-sided 0.05 significance level. The 12.5 mg dose was compared to placebo only if the comparison of the 25mg dose to placebo was significant.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-0.72 to -0.30
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 26. For comparison of either alogliptin dose vs. placebo (2-sample t test), study sample size >=390 participants had 95% power to detect a treatment difference as small as 0.4% in the per protocol analysis set assuming a standard deviation of 0.8%, a 2-sided test at 0.05 significance level and >=80% of subjects meeting the per protocol criteria.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments A step-down strategy was used for the primary analysis. First, the 25mg dose was compared to placebo at the 2-sided 0.05 significance level. The 12.5 mg dose was compared to placebo only if the comparison of the 25mg dose to placebo was significant.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.59
Confidence Interval (2-Sided) 95%
-0.80 to -0.37
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
2.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (Week 4).
Hide Description The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 4 and Glycosylated Hemoglobin collected at baseline.
Time Frame Baseline and Week 4.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and who had an HbA1c measurement at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 114 116 116
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.26  (0.045) -0.47  (0.045) -0.58  (0.045)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.34 to -0.09
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.45 to -0.20
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
3.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (Week 8).
Hide Description The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 8 and Glycosylated Hemoglobin collected at baseline.
Time Frame Baseline and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 126 130 126
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.27  (0.061) -0.76  (0.060) -0.84  (0.062)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-0.65 to -0.31
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.56
Confidence Interval (2-Sided) 95%
-0.73 to -0.39
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
4.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (Week 12).
Hide Description The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 and Glycosylated Hemoglobin collected at baseline.
Time Frame Baseline and Week 12.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 126 130 126
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.27  (0.073) -0.84  (0.072) -0.81  (0.073)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.57
Confidence Interval (2-Sided) 95%
-0.77 to -0.37
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.54
Confidence Interval (2-Sided) 95%
-0.75 to -0.34
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
5.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (Week 16).
Hide Description The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 16 and Glycosylated Hemoglobin collected at baseline.
Time Frame Baseline and Week 16.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 126 130 126
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.22  (0.076) -0.80  (0.074) -0.76  (0.076)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-0.79 to -0.37
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.54
Confidence Interval (2-Sided) 95%
-0.75 to -0.33
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
6.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (Week 20).
Hide Description The change in the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 20 and Glycosylated Hemoglobin collected at baseline.
Time Frame Baseline and Week 20.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 126 130 126
Least Squares Mean (Standard Error)
Unit of Measure: percentage of Glycosylated Hemoglobin
-0.17  (0.078) -0.76  (0.076) -0.74  (0.078)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.59
Confidence Interval (2-Sided) 95%
-0.80 to -0.37
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.57
Confidence Interval (2-Sided) 95%
-0.79 to -0.35
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
7.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 1).
Hide Description The change between the value of fasting plasma glucose collected at final visit or week 1 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 1.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 1. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 107 121 111
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
6.3  (5.40) -5.0  (5.07) -9.9  (5.33)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 1. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.128
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -11.3
Confidence Interval (2-Sided) 95%
-25.9 to 3.3
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 1. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.034
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -16.1
Confidence Interval (2-Sided) 95%
-31.1 to -1.2
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
8.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 2).
Hide Description The change between the value of fasting plasma glucose collected at week 2 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 2.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 2. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 115 127 119
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
1.0  (5.09) -3.1  (4.84) -11.4  (5.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 2. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.563
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.1
Confidence Interval (2-Sided) 95%
-17.9 to 9.7
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 2. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.084
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -12.4
Confidence Interval (2-Sided) 95%
-26.4 to 1.7
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
9.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 4).
Hide Description The change between the value of fasting plasma glucose collected at week 4 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 4.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 119 128 120
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
5.3  (5.28) -5.0  (5.08) -12.1  (5.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.160
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -10.3
Confidence Interval (2-Sided) 95%
-24.7 to 4.1
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -17.4
Confidence Interval (2-Sided) 95%
-32.1 to -2.8
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
10.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 8).
Hide Description The change between the value of fasting plasma glucose collected at week 8 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 124 131 126
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
5.4  (5.42) -13.5  (5.26) -14.1  (5.39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 8. The treatment effect was be evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -18.9
Confidence Interval (2-Sided) 95%
-33.7 to -4.0
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -19.5
Confidence Interval (2-Sided) 95%
-34.5 to -4.5
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
11.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 12).
Hide Description The change between the value of fasting plasma glucose collected at week 12 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 12.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 127 131 128
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
-1.4  (5.47) -5.2  (5.38) -2.9  (5.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.624
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.8
Confidence Interval (2-Sided) 95%
-18.9 to 11.3
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.853
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-16.7 to 13.8
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
12.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 16).
Hide Description The change between the value of fasting plasma glucose collected at week 16 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 16.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 127 131 128
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
4.6  (5.38) -5.3  (5.29) -6.3  (5.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.190
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -9.9
Confidence Interval (2-Sided) 95%
-24.7 to 4.9
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 16. The treatment effect was be evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.154
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -10.9
Confidence Interval (2-Sided) 95%
-25.8 to 4.1
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
13.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 20).
Hide Description The change between the value of fasting plasma glucose collected at week 20 and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 20.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 127 131 128
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
8.6  (5.45) -4.2  (5.36) -11.3  (5.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.097
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -12.7
Confidence Interval (2-Sided) 95%
-27.8 to 2.3
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -19.9
Confidence Interval (2-Sided) 95%
-35.1 to -4.7
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
14.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (Week 26).
Hide Description The change between the value of fasting plasma glucose collected at week 26 or final visit and fasting plasma glucose collected at baseline.
Time Frame Baseline and Week 26.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 127 131 128
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
5.8  (5.69) 2.3  (5.59) -11.7  (5.69)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.662
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.5
Confidence Interval (2-Sided) 95%
-19.2 to 12.2
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -17.6
Confidence Interval (2-Sided) 95%
-33.4 to -1.7
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
15.Secondary Outcome
Title Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL).
Hide Description The number of participants with a fasting plasma glucose value greater than or equal to 200 mg per dL during the 26 week study.
Time Frame 26 Weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 fasting plasma glucose measurement after baseline.
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 128 131 128
Measure Type: Number
Unit of Measure: participants
105 99 86
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in number of participants with marked hyperglycemia. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.551
Confidence Interval (2-Sided) 95%
0.286 to 1.063
Estimation Comments Odds Ratio (OR) is alogliptin arm versus placebo. OR <1.0 indicates lower incidence compared to placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in number of participants with marked hyperglycemia. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.364
Confidence Interval (2-Sided) 95%
0.191 to 0.695
Estimation Comments Odds Ratio (OR) is alogliptin arm versus placebo. OR <1.0 indicates lower incidence compared to placebo.
16.Secondary Outcome
Title Number of Participants Requiring Rescue.
Hide Description The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 26 week study.
Time Frame 26 Weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who completed at least 1 study visit after baseline.
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 129 131 128
Measure Type: Number
Unit of Measure: participants
52 27 25
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in number of participants requiring rescue. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.350
Confidence Interval (2-Sided) 95%
0.198 to 0.619
Estimation Comments Odds Ratio (OR) is alogliptin arm versus placebo arm. OR <1.0 indicates lower incidence compared to placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in number of participants requiring rescue. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.339
Confidence Interval (2-Sided) 95%
0.189 to 0.608
Estimation Comments Odds Ratio (OR) is alogliptin arm versus placebo. OR <1.0 indicates lower incidence compared to placebo.
17.Secondary Outcome
Title Change From Baseline in C-peptide (Week 4).
Hide Description The change between the value of C-peptide collected at week 4 and C-peptide collected at baseline.
Time Frame Baseline and Week 4.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 99 111 109
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
-0.023  (0.1062) 0.132  (0.1001) 0.453  (0.1014)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-Peptide at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.286
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.156
Confidence Interval (2-Sided) 95%
-0.131 to 0.443
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value .477
Confidence Interval (2-Sided) 95%
0.188 to 0.765
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
18.Secondary Outcome
Title Change From Baseline in C-peptide (Week 8).
Hide Description The change between the value of C-peptide collected at week 8 and C-peptide collected at baseline.
Time Frame Baseline and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 121 130 123
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
-0.024  (0.1224) 0.178  (0.1180) 0.348  (0.1220)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-Peptide at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.236
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.202
Confidence Interval (2-Sided) 95%
-0.132 to 0.536
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-Peptide at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.032
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.372
Confidence Interval (2-Sided) 95%
0.032 to 0.712
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
19.Secondary Outcome
Title Change From Baseline in C-peptide (Week 12).
Hide Description The change between the value of C-peptide collected at week 12 and C-peptide collected at baseline.
Time Frame Baseline and Week 12.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 124 130 126
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
0.207  (0.1558) 0.333  (0.1521) 0.390  (0.1553)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.562
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.126
Confidence Interval (2-Sided) 95%
-0.302 to 0.554
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.407
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.183
Confidence Interval (2-Sided) 95%
-0.251 to 0.616
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
20.Secondary Outcome
Title Change From Baseline in C-peptide (Week 16).
Hide Description The change between the value of C-peptide collected at week 16 and C-peptide collected at baseline.
Time Frame Baseline and Week 16.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 124 130 126
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
0.241  (0.1536) 0.319  (0.1500) 0.396  (0.1532)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.716
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.078
Confidence Interval (2-Sided) 95%
-0.344 to 0.500
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.474
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.156
Confidence Interval (2-Sided) 95%
-0.272 to 0.583
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
21.Secondary Outcome
Title Change From Baseline in C-peptide (Week 20).
Hide Description The change between the value of C-peptide collected at week 20 and C-peptide collected at baseline.
Time Frame Baseline and Week 20.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 124 130 126
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
0.239  (0.1467) 0.318  (0.1432) 0.281  (0.1463)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.700
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.079
Confidence Interval (2-Sided) 95%
-0.324 to 0.482
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.839
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.042
Confidence Interval (2-Sided) 95%
-0.366 to 0.450
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
22.Secondary Outcome
Title Change From Baseline in C-peptide (Week 26).
Hide Description The change between the value of C-peptide collected at week 26 or final visit and C-peptide collected at baseline.
Time Frame Baseline and Week 26.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 124 130 126
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
-0.083  (0.1192) 0.199  (0.1164) 0.042  (0.1189)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.091
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.282
Confidence Interval (2-Sided) 95%
-0.045 to 0.610
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.459
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.125
Confidence Interval (2-Sided) 95%
-0.207 to 0.457
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
23.Secondary Outcome
Title Number of Participants With Glycosylated Hemoglobin ≤ 6.5%.
Hide Description The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5% during the 26 week study.
Time Frame Baseline and Week 26.
Hide Outcome Measure Data
Hide Analysis Population Description

Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who completed at least 1 HbA1c measurement after baseline.

Due to no participants in the placebo arm achieved HbA1c ≤ 6.5%, the odds ratio of alogliptin to placebo and 95% CI were not estimable from the logistic regression.

Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 129 131 129
Measure Type: Number
Unit of Measure: participants
0 3 3
24.Secondary Outcome
Title Number of Participants With Glycosylated Hemoglobin ≤ 7.0%.
Hide Description The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.0% during the 26 week study.
Time Frame Baseline and Week 26.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 129 131 129
Measure Type: Number
Unit of Measure: participants
1 11 10
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c ≤7.0%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 12.650
Confidence Interval (2-Sided) 95%
1.589 to 100.682
Estimation Comments Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c ≤7.0%. The treatment effect was evaluated as a contrast of each active dose versus placebo was evaluated inferentially with a Wald test at the 0.05 significance level
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 11.255
Confidence Interval (2-Sided) 95%
1.401 to 90.379
Estimation Comments Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.
25.Secondary Outcome
Title Number of Participants With Glycosylated Hemoglobin ≤ 7.5%.
Hide Description The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.5% during the 26 week study.
Time Frame Baseline and Week 26.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 129 131 129
Measure Type: Number
Unit of Measure: participants
5 22 33
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c ≤7.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method ANCOVA
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.777
Confidence Interval (2-Sided) 95%
2.047 to 16.305
Estimation Comments Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c ≤7.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 9.784
Confidence Interval (2-Sided) 95%
3.540 to 27.039
Estimation Comments Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.
26.Secondary Outcome
Title Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%.
Hide Description The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5% during the 26 week study.
Time Frame Baseline and Week 26.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 129 131 129
Measure Type: Number
Unit of Measure: participants
40 70 70
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥0.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.674
Confidence Interval (2-Sided) 95%
1.579 to 4.530
Estimation Comments Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥0.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.819
Confidence Interval (2-Sided) 95%
1.653 to 4.808
Estimation Comments Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.
27.Secondary Outcome
Title Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%.
Hide Description The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.0% during the 26 week study.
Time Frame Baseline and Week 26.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 129 131 129
Measure Type: Number
Unit of Measure: participants
17 41 47
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥1.0%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.163
Confidence Interval (2-Sided) 95%
1.651 to 6.060
Estimation Comments Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥1.0%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.989
Confidence Interval (2-Sided) 95%
2.083 to 7.640
Estimation Comments Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.
28.Secondary Outcome
Title Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%.
Hide Description The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.5% during the 26 week study.
Time Frame Baseline and Week 26.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 129 131 129
Measure Type: Number
Unit of Measure: participants
6 22 23
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥1.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.550
Confidence Interval (2-Sided) 95%
1.732 to 11.953
Estimation Comments Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥1.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments No multiplicity adjustments.
Method Regression, Logistic
Comments Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.580
Confidence Interval (2-Sided) 95%
1.740 to 12.052
Estimation Comments Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.
29.Secondary Outcome
Title Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%.
Hide Description The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 2.0% during the 26 week study.
Time Frame Baseline and Week 26.
Hide Outcome Measure Data
Hide Analysis Population Description

Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.

Due to no participants in the placebo arm achieved HbA1c decrease from baseline ≥2.0%, the odds ratio of alogliptin to placebo and 95% CI were not estimable from the logistic regression.

Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 129 131 129
Measure Type: Number
Unit of Measure: participants
0 11 11
30.Secondary Outcome
Title Change From Baseline in Body Weight (Week 8).
Hide Description The change between Body Weight measured at week 8 and Body Weight measured at baseline.
Time Frame Baseline and Week 8.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 118 125 121
Least Squares Mean (Standard Error)
Unit of Measure: kg
0.39  (0.191) 0.10  (0.185) 0.18  (0.189)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.291
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.81 to 0.24
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.439
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.74 to 0.32
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
31.Secondary Outcome
Title Change From Baseline in Body Weight (Week 12).
Hide Description The change between Body Weight measured at week 12 and Body Weight measured at baseline.
Time Frame Baseline and Week 12.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 121 127 123
Least Squares Mean (Standard Error)
Unit of Measure: kg
0.50  (0.221) 0.44  (0.215) 0.31  (0.219)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.841
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.67 to 0.55
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.556
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.80 to 0.43
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
32.Secondary Outcome
Title Change From Baseline in Body Weight (Week 20).
Hide Description The change between Body Weight measured at week 20 and Body Weight measured at baseline.
Time Frame Baseline and Week 20.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 121 127 124
Least Squares Mean (Standard Error)
Unit of Measure: kg
0.73  (0.231) 0.55  (0.225) 0.45  (0.229)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.586
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.81 to 0.46
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.404
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.91 to 0.37
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
33.Secondary Outcome
Title Change From Baseline in Body Weight (Week 26).
Hide Description The change between Body Weight measured at week 26 or final visit and Body Weight measured at baseline.
Time Frame Baseline and Week 26.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description:
Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Overall Number of Participants Analyzed 121 127 124
Least Squares Mean (Standard Error)
Unit of Measure: kg
0.63  (0.244) 0.68  (0.237) 0.60  (0.241)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 12.5 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.874
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.62 to 0.72
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin 25 mg QD
Comments The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.948
Comments No multiplicity adjustments.
Method ANCOVA
Comments ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.70 to 0.65
Estimation Comments Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.
Time Frame Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious event) after the last dose of double-blind drug.
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Hide Arm/Group Description Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks. Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks. Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
All-Cause Mortality
Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/129 (4.65%)   8/131 (6.11%)   7/129 (5.43%) 
Cardiac disorders       
Angina unstable  1  1/129 (0.78%)  0/131 (0.00%)  1/129 (0.78%) 
Atrial fibrillation  1  0/129 (0.00%)  2/131 (1.53%)  0/129 (0.00%) 
Coronary artery disease  1  0/129 (0.00%)  1/131 (0.76%)  0/129 (0.00%) 
Gastrointestinal disorders       
Diverticulitis intestinal haemorrhagic  1  1/129 (0.78%)  0/131 (0.00%)  0/129 (0.00%) 
Pancreatitis  1  0/129 (0.00%)  1/131 (0.76%)  0/129 (0.00%) 
Upper gastrointestinal haemorrhage  1  0/129 (0.00%)  0/131 (0.00%)  1/129 (0.78%) 
General disorders       
Sudden death  1  0/129 (0.00%)  1/131 (0.76%)  0/129 (0.00%) 
Hepatobiliary disorders       
Cholecystitis  1  0/129 (0.00%)  2/131 (1.53%)  0/129 (0.00%) 
Immune system disorders       
Hypersensitivity  1  0/129 (0.00%)  0/131 (0.00%)  1/129 (0.78%) 
Infections and infestations       
Pyelonephritis  1  0/129 (0.00%)  0/131 (0.00%)  1/129 (0.78%) 
Scrotal abscess  1  0/129 (0.00%)  1/131 (0.76%)  0/129 (0.00%) 
Staphylococcal infection  1  0/129 (0.00%)  0/131 (0.00%)  1/129 (0.78%) 
Injury, poisoning and procedural complications       
Incisional hernia  1  1/129 (0.78%)  0/131 (0.00%)  0/129 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/129 (0.00%)  0/131 (0.00%)  1/129 (0.78%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cervix carcinoma  1  1/129 (0.78%)  0/131 (0.00%)  0/129 (0.00%) 
Nervous system disorders       
Demyelination  1  1/129 (0.78%)  0/131 (0.00%)  0/129 (0.00%) 
Hypoglycaemic coma  1  0/129 (0.00%)  0/131 (0.00%)  1/129 (0.78%) 
Ischaemic stroke  1  1/129 (0.78%)  0/131 (0.00%)  0/129 (0.00%) 
Sciatica  1  0/129 (0.00%)  1/131 (0.76%)  0/129 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Placebo Alogliptin 12.5 mg QD Alogliptin 25 mg QD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   54/129 (41.86%)   58/131 (44.27%)   50/129 (38.76%) 
Gastrointestinal disorders       
Abdominal pain  1  1/129 (0.78%)  1/131 (0.76%)  6/129 (4.65%) 
Diarrhoea  1  7/129 (5.43%)  1/131 (0.76%)  8/129 (6.20%) 
Nausea  1  3/129 (2.33%)  4/131 (3.05%)  6/129 (4.65%) 
Vomiting  1  4/129 (3.10%)  0/131 (0.00%)  3/129 (2.33%) 
General disorders       
Oedema peripheral  1  4/129 (3.10%)  4/131 (3.05%)  7/129 (5.43%) 
Infections and infestations       
Bronchitis  1  4/129 (3.10%)  3/131 (2.29%)  1/129 (0.78%) 
Influenza  1  3/129 (2.33%)  4/131 (3.05%)  3/129 (2.33%) 
Nasopharyngitis  1  6/129 (4.65%)  5/131 (3.82%)  8/129 (6.20%) 
Upper respiratory tract  1  4/129 (3.10%)  6/131 (4.58%)  4/129 (3.10%) 
Urinary tract infection  1  10/129 (7.75%)  8/131 (6.11%)  9/129 (6.98%) 
Metabolism and nutrition disorders       
Hypertriglyceridaemia  1  3/129 (2.33%)  5/131 (3.82%)  2/129 (1.55%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  3/129 (2.33%)  9/131 (6.87%)  3/129 (2.33%) 
Back pain  1  2/129 (1.55%)  2/131 (1.53%)  6/129 (4.65%) 
Nervous system disorders       
Dizziness  1  2/129 (1.55%)  5/131 (3.82%)  1/129 (0.78%) 
Headache  1  6/129 (4.65%)  7/131 (5.34%)  4/129 (3.10%) 
Psychiatric disorders       
Insomnia  1  0/129 (0.00%)  4/131 (3.05%)  1/129 (0.78%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  4/129 (3.10%)  2/131 (1.53%)  2/129 (1.55%) 
Skin and subcutaneous tissue disorders       
Pruritus  1  0/129 (0.00%)  0/131 (0.00%)  4/129 (3.10%) 
Vascular disorders       
Hypertension  1  6/129 (4.65%)  5/131 (3.82%)  2/129 (1.55%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
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.
No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Name/Title: Sr. VP, Clinical Science
Organization: Takeda Global Research and Development Center, Inc.
Phone: 800-778-2860
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00286429     History of Changes
Other Study ID Numbers: SYR-322-INS-011
2005-004671-38 ( EudraCT Number )
U1111-1113-8369 ( Registry Identifier: WHO )
First Submitted: February 1, 2006
First Posted: February 3, 2006
Results First Submitted: June 8, 2011
Results First Posted: August 12, 2011
Last Update Posted: February 3, 2012