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Efficacy and Safety of Alogliptin in Participants With Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT01289119
Recruitment Status : Completed
First Posted : February 3, 2011
Results First Posted : March 22, 2013
Last Update Posted : March 22, 2013
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, Type 2
Interventions Drug: Alogliptin
Drug: Placebo to alogliptin
Drug: Metformin
Drug: Pioglitazone
Enrollment 506
Recruitment Details Participants took part in the study at 30 investigative sites in China, Taiwan province and Hong Kong from 23 December 2010 to 19 December 2011.
Pre-assignment Details Participants with a historical diagnosis of Type 2 diabetes mellitus who were experiencing inadequate glycemic control were stratified into 1 of the 3 therapy groups based upon their background antidiabetic therapy before being randomized 1:1 to receive either alogliptin 25 mg once daily or matching placebo once daily.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks. Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks. Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks. Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks. Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Period Title: Overall Study
Started 93 92 98 99 63 61
Treated 92 [1] 92 98 99 63 61
Completed 84 83 89 93 58 57
Not Completed 9 9 9 6 5 4
Reason Not Completed
Adverse Event             2             1             0             2             1             0
Major Protocol Deviation             2             1             3             0             2             1
Lost to Follow-up             0             3             0             0             0             1
Withdrawal by Subject             4             2             4             3             1             1
Pregnancy             0             1             0             0             0             0
Lack of Efficacy             0             1             1             1             1             1
Other             1             0             1             0             0             0
[1]
Patients who took at least one dose of double-blind study drug.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy Total
Hide Arm/Group Description Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks. Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks. Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks. Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks. Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks. Total of all reporting groups
Overall Number of Baseline Participants 93 92 98 99 63 61 506
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 93 participants 92 participants 98 participants 99 participants 63 participants 61 participants 506 participants
53.1  (8.88) 51.6  (10.41) 53.2  (9.46) 53.0  (9.88) 51.8  (10.37) 52.6  (9.44) 52.6  (9.71)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 93 participants 92 participants 98 participants 99 participants 63 participants 61 participants 506 participants
<65 Years 81 80 86 85 56 52 440
≥65 years 12 12 12 14 7 9 66
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 93 participants 92 participants 98 participants 99 participants 63 participants 61 participants 506 participants
Female
39
  41.9%
37
  40.2%
50
  51.0%
48
  48.5%
24
  38.1%
33
  54.1%
231
  45.7%
Male
54
  58.1%
55
  59.8%
48
  49.0%
51
  51.5%
39
  61.9%
28
  45.9%
275
  54.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 93 participants 92 participants 98 participants 99 participants 63 participants 61 participants 506 participants
93 92 98 99 63 61 506
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 93 participants 92 participants 98 participants 99 participants 63 participants 61 participants 506 participants
Taiwan 1 0 2 3 0 0 6
Hong Kong 1 2 2 4 0 0 9
China 91 90 94 92 63 61 491
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 93 participants 92 participants 98 participants 99 participants 63 participants 61 participants 506 participants
165.4  (7.19) 165.9  (8.61) 164.8  (8.47) 165.7  (9.06) 166.2  (8.87) 163.0  (7.06) 165.2  (8.31)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 93 participants 92 participants 98 participants 99 participants 63 participants 61 participants 506 participants
70.86  (10.464) 71.16  (11.065) 69.67  (11.792) 71.20  (13.473) 72.44  (11.989) 67.59  (11.989) 70.55  (11.856)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 93 participants 92 participants 98 participants 99 participants 63 participants 61 participants 506 participants
25.86  (3.002) 25.79  (3.086) 25.54  (2.876) 25.75  (3.122) 26.13  (3.031) 25.32  (3.223) 25.73  (3.042)
Diabetes duration  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 93 participants 92 participants 98 participants 99 participants 63 participants 61 participants 506 participants
2.12  (2.845) 1.86  (2.369) 5.33  (3.873) 5.38  (4.335) 4.85  (4.724) 5.80  (5.300) 4.11  (4.215)
HbA1c  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 93 participants 92 participants 98 participants 99 participants 63 participants 61 participants 506 participants
<8.0% 47 48 54 55 34 32 270
≥8.0% 46 44 44 44 29 29 236
Stable Daily Dose of Metformin   [1] 
Mean (Standard Deviation)
Unit of measure:  Mg
Number Analyzed 93 participants 92 participants 98 participants 99 participants 63 participants 61 participants 506 participants
NA [2]   (NA) NA [2]   (NA) 1484.2  (451.09) 1472.2  (417.31) 1355.0  (431.80) 1295.0  (506.82) 1426.6  (450.90)
[1]
Measure Description: Participant population for this measure for each treatment arm: 0, 0, 98, 99, 50, 50; Total population: 297
[2]
Participants in this arm were not taking Metformin
Stable Daily Dose of Pioglitazone   [1] 
Mean (Standard Deviation)
Unit of measure:  Mg
Number Analyzed 93 participants 92 participants 98 participants 99 participants 63 participants 61 participants 506 participants
NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 21.9  (11.37) 20.2  (7.19) 21.0  (9.55)
[1]
Measure Description: Participant population for this measure for each treatment arm: 0, 0, 0, 0, 63, 61; Total population: 124
[2]
Participants in this arm were not taking Pioglitazone
1.Primary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Hide Description The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 16. Least squares means are derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect, and baseline HbA1c as a covariate for the monotherapy, baseline HbA1c with baseline metformin dose as covariates for the metformin therapy, baseline HbA1c with baseline metformin therapy status and baseline pioglitazone dose as covariates for the pioglitazone therapy.
Time Frame Baseline and Week 16.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all patients who received at least one dose of double-blind study drug and who had a baseline assessment and at least one post-baseline HbA1c assessment. Last observation carried forward was utilized.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description:
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Overall Number of Participants Analyzed 90 90 97 98 63 60
Least Squares Mean (Standard Error)
Unit of Measure: percentage glycosylated hemoglobin
-0.42  (0.074) -0.99  (0.074) -0.22  (0.065) -0.91  (0.065) -0.25  (0.097) -0.76  (0.101)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Alogliptin Monotherapy
Comments The analysis was conducted at the 2-sided 5% significance level without a multiplicity adjustment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a fixed effect, and baseline HbA1c as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-0.78 to -0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Metformin, Metformin + Alogliptin Add-on Therapy
Comments The analysis was conducted at the 2-sided 5% significance level without a multiplicity adjustment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments ANCOVA model with treatment as a fixed effect, and baseline HbA1c with baseline metformin dose as covariates.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.69
Confidence Interval (2-Sided) 95%
-0.87 to -0.51
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pioglitazone, Pioglitazone + Alogliptin Add-on Therapy
Comments The analysis was conducted at the 2-sided 5% significance level without a multiplicity adjustment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a fixed effect, and baseline HbA1c with baseline metformin therapy status and baseline pioglitazone dose as covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-0.75 to -0.28
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in HbA1c Over Time
Hide Description The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at Weeks 4, 8 and 12. Least squares means are derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect, and baseline HbA1c as a covariate for the monotherapy, baseline HbA1c with baseline metformin dose as covariates for the metformin therapy, baseline HbA1c with baseline metformin therapy status and baseline pioglitazone dose as covariates for the pioglitazone therapy.
Time Frame Baseline and Weeks 4, 8 and 12.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all patients who received at least one dose of double-blind study drug and who had a baseline assessment and at least one post-baseline HbA1c assessment. Last observation carried forward was utilized.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description:
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Overall Number of Participants Analyzed 92 92 98 99 63 61
Least Squares Mean (Standard Error)
Unit of Measure: percentage glycosylated hemoglobin
Week 4 (n=90, 88, 97, 98, 63, 60) -0.24  (0.059) -0.56  (0.059) -0.15  (0.036) -0.43  (0.036) -0.09  (0.064) -0.44  (0.066)
Week 8 (n=90, 90, 97, 98, 63, 60) -0.39  (0.068) -0.86  (0.068) -0.15  (0.057) -0.66  (0.057) -0.31  (0.094) -0.70  (0.098)
Week 12 (n=90, 90, 97, 98, 63, 60) -0.41  (0.078) -0.99  (0.078) -0.24  (0.069) -0.86  (0.068) -0.25  (0.102) -0.77  (0.106)
3.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose Over Time
Hide Description The change from Baseline in fasting plasma glucose (FPG) at Weeks 4, 8, 12 and 16. Least squares means are derived from an ANCOVA model with treatment as a fixed effect, and baseline FPG as a covariate for the monotherapy, baseline FPG with baseline metformin dose as covariates for the metformin therapy, baseline FPG with baseline metformin therapy status and baseline pioglitazone dose as covariates for the pioglitazone therapy.
Time Frame Baseline and Weeks 4, 8, 12 and 16.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all patients who received at least one dose of double-blind study drug and who had a baseline assessment and at least one post-baseline FPG assessment. Last observation carried forward was utilized.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description:
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Overall Number of Participants Analyzed 92 92 98 99 63 61
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
Week 4 (n=89, 87, 97, 97, 63, 60) -0.331  (0.1221) -0.719  (0.1235) -0.251  (0.1454) -0.985  (0.1454) 0.284  (0.2505) -0.985  (0.2603)
Week 8 (n=89, 89, 97, 97, 63, 60) -0.330  (0.1224) -1.015  (0.1224) -0.235  (0.1397) -1.265  (0.1397) -0.038  (0.2503) -0.924  (0.2600)
Week 12 (n=89, 89, 97, 97, 63, 60) -0.411  (0.1515) -1.123  (0.1515) -0.335  (0.1600) -1.270  (0.1600) -0.187  (0.2484) -1.177  (0.2581)
Week 16 (n=89, 89, 97, 97, 63, 60) -0.317  (0.1556) -1.243  (0.1556) -0.512  (0.1565) -1.240  (0.1565) -0.114  (0.2579) -1.070  (0.2679)
4.Secondary Outcome
Title Percentage of Participants With Marked Hyperglycemia
Hide Description Marked Hyperglycemia was defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.1 mmol/L).
Time Frame Randomization to Week 16.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all patients who received at least one dose of double-blind study drug and who had a baseline assessment and at least one post-baseline assessment.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description:
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Overall Number of Participants Analyzed 89 89 97 97 63 60
Measure Type: Number
Unit of Measure: percentage of participants
16.9 4.5 25.8 13.4 23.8 8.3
5.Secondary Outcome
Title Change From Baseline in Body Weight
Hide Description The change between body weight measured at Baseline and body weight measured at Weeks 8 and 16. The least squares means are derived from an ANCOVA model with treatment as a fixed effect, and baseline body weight as a covariate for the monotherapy, baseline body weight with baseline metformin dose as covariates for the add-on to metformin therapy, baseline body weight with baseline metformin therapy status and baseline pioglitazone dose as covariates for the add-on to pioglitazone therapy.
Time Frame Baseline and Weeks 8 and 16.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all patients who received at least one dose of double-blind study drug and who had a baseline assessment and at least one post-baseline weight assessment. Last observation carried forward was utilized.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description:
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Overall Number of Participants Analyzed 92 92 98 99 63 61
Least Squares Mean (Standard Error)
Unit of Measure: kg
Week 8 (n=87, 86, 94, 96, 63, 59) -1.04  (0.210) -0.71  (0.211) -0.82  (0.170) -0.43  (0.168) -0.74  (0.286) -0.15  (0.304)
Week 16 (n=88, 87, 94, 96, 63, 59) -1.55  (0.244) -0.89  (0.245) -1.06  (0.219) -0.76  (0.217) -0.68  (0.364) -0.10  (0.388)
6.Secondary Outcome
Title Percentage of Participants With HbA1c ≤6.5% at Week 16
Hide Description Clinical response was assessed by the percentage of participants with HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) less than or equal to 6.5% at Week 16.
Time Frame Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all patients who received at least one dose of double-blind study drug and who had a baseline assessment and at least one post-baseline HbA1c assessment. Last observation carried forward was utilized.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description:
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Overall Number of Participants Analyzed 90 90 97 98 63 60
Measure Type: Number
Unit of Measure: percentage of participants
12.2 36.7 4.1 21.4 9.5 30.0
7.Secondary Outcome
Title Percentage of Participants With HbA1c ≤7.0% at Week 16
Hide Description Clinical response was assessed by the percentage of participants with HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) less than or equal to 7.0% at Week 16.
Time Frame Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all patients who received at least one dose of double-blind study drug and who had a baseline assessment and at least one post-baseline HbA1c assessment. Last observation carried forward was utilized.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description:
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Overall Number of Participants Analyzed 90 90 97 98 63 60
Measure Type: Number
Unit of Measure: percentage of participants
30.0 63.3 25.8 55.1 31.7 61.7
8.Secondary Outcome
Title Percentage of Participants With HbA1c ≤7.5% at Week 16
Hide Description Clinical response was assessed by the percentage of participants with HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) less than or equal to 7.5% at Week 16.
Time Frame Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all patients who received at least one dose of double-blind study drug and who had a baseline assessment and at least one post-baseline HbA1c assessment. Last observation carried forward was utilized.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description:
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Overall Number of Participants Analyzed 90 90 97 98 63 60
Measure Type: Number
Unit of Measure: percentage of participants
53.3 81.1 50.5 80.6 47.6 85.0
9.Secondary Outcome
Title Percentage of Participants With a Decrease in HbA1c ≥ 0.5%
Hide Description Clinical response was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5% at Week 16.
Time Frame Baseline and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all patients who received at least one dose of double-blind study drug and who had a baseline assessment and at least one post-baseline HbA1c assessment. Last observation carried forward was utilized.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description:
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Overall Number of Participants Analyzed 90 90 97 98 63 60
Measure Type: Number
Unit of Measure: percentage of participants
41.1 84.4 37.1 70.4 42.9 76.7
10.Secondary Outcome
Title Percentage of Participants With a Decrease in HbA1c ≥1.0%
Hide Description Clinical response was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.0% at Week 16.
Time Frame Baseline and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all patients who received at least one dose of double-blind study drug and who had a baseline assessment and at least one post-baseline HbA1c assessment. Last observation carried forward was utilized.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description:
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Overall Number of Participants Analyzed 90 90 97 98 63 60
Measure Type: Number
Unit of Measure: percentage of participants
20.0 50.0 9.3 45.9 19.0 46.7
11.Secondary Outcome
Title Percentage of Participants With a Decrease in HbA1c ≥1.5%
Hide Description Clinical response was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5% at Week 16.
Time Frame Baseline and Week 16.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all patients who received at least one dose of double-blind study drug and who had a baseline assessment and at least one post-baseline HbA1c assessment. Last observation carried forward was utilized.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description:
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Overall Number of Participants Analyzed 90 90 97 98 63 60
Measure Type: Number
Unit of Measure: percentage of participants
7.8 23.3 1.0 22.4 7.9 8.3
12.Secondary Outcome
Title Percentage of Participants With a Decrease in HbA1c ≥2.0%
Hide Description Clinical response was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0% at Week 16.
Time Frame Baseline and Week 16.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The full analysis set, consisting of all patients who received at least one dose of double-blind study drug and who had a baseline assessment and at least one post-baseline HbA1c assessment. Last observation carried forward was utilized.
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description:
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
Overall Number of Participants Analyzed 90 90 97 98 63 60
Measure Type: Number
Unit of Measure: percentage of participants
2.2 8.9 0.0 9.2 1.6 3.3
Time Frame Treatment-emergent adverse events (TEAE) were defined as any adverse events that started on or after the date of the first dose of double-blind study drug and within 14 days after the date of the last dose of double-blind study drug.
Adverse Event Reporting Description The investigator had to document any occurrence of adverse events at each visit, and the occurrence of abnormal laboratory findings at applicable visits. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Hide Arm/Group Description Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks. Participants continued to receive their stable dose of Metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks. Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks. Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks. Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
All-Cause Mortality
Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/92 (2.17%)   2/92 (2.17%)   3/98 (3.06%)   0/99 (0.00%)   0/63 (0.00%)   1/61 (1.64%) 
Cardiac disorders             
Atrial fibrillation  1  0/92 (0.00%)  0/92 (0.00%)  1/98 (1.02%)  0/99 (0.00%)  0/63 (0.00%)  0/61 (0.00%) 
Coronary artery disease  1  0/92 (0.00%)  0/92 (0.00%)  1/98 (1.02%)  0/99 (0.00%)  0/63 (0.00%)  0/61 (0.00%) 
Gastrointestinal disorders             
Pancreatitis acute  1  1/92 (1.09%)  0/92 (0.00%)  0/98 (0.00%)  0/99 (0.00%)  0/63 (0.00%)  0/61 (0.00%) 
Hepatobiliary disorders             
Cholangitis acute  1  0/92 (0.00%)  1/92 (1.09%)  0/98 (0.00%)  0/99 (0.00%)  0/63 (0.00%)  0/61 (0.00%) 
Infections and infestations             
Cellulitis  1  1/92 (1.09%)  0/92 (0.00%)  0/98 (0.00%)  0/99 (0.00%)  0/63 (0.00%)  0/61 (0.00%) 
Musculoskeletal and connective tissue disorders             
Intervertebral disc protrusion  1  0/92 (0.00%)  0/92 (0.00%)  1/98 (1.02%)  0/99 (0.00%)  0/63 (0.00%)  0/61 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Intraductal papilloma of breast  1  0/92 (0.00%)  1/92 (1.09%)  0/98 (0.00%)  0/99 (0.00%)  0/63 (0.00%)  0/61 (0.00%) 
Nervous system disorders             
Lacunar infarction  1  0/92 (0.00%)  0/92 (0.00%)  0/98 (0.00%)  0/99 (0.00%)  0/63 (0.00%)  1/61 (1.64%) 
Vascular disorders             
Hypertension  1  0/92 (0.00%)  0/92 (0.00%)  1/98 (1.02%)  0/99 (0.00%)  0/63 (0.00%)  0/61 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 14.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Alogliptin Monotherapy Metformin Metformin + Alogliptin Add-on Therapy Pioglitazone Pioglitazone + Alogliptin Add-on Therapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/92 (11.96%)   12/92 (13.04%)   8/98 (8.16%)   7/99 (7.07%)   14/63 (22.22%)   18/61 (29.51%) 
Infections and infestations             
Upper respiratory tract infection  1  3/92 (3.26%)  5/92 (5.43%)  5/98 (5.10%)  3/99 (3.03%)  6/63 (9.52%)  2/61 (3.28%) 
Urinary tract infection  1  6/92 (6.52%)  2/92 (2.17%)  2/98 (2.04%)  2/99 (2.02%)  1/63 (1.59%)  4/61 (6.56%) 
Investigations             
Blood triglycerides increased  1  1/92 (1.09%)  2/92 (2.17%)  2/98 (2.04%)  2/99 (2.02%)  4/63 (6.35%)  0/61 (0.00%) 
Metabolism and nutrition disorders             
Hyperlipidaemia  1  1/92 (1.09%)  6/92 (6.52%)  0/98 (0.00%)  0/99 (0.00%)  4/63 (6.35%)  13/61 (21.31%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 14.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay 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: NCT01289119     History of Changes
Other Study ID Numbers: SYR-322_02
U1111-1118-3681 ( Registry Identifier: WHO )
SYR-322_308 ( Other Identifier: Takeda ID )
First Submitted: February 1, 2011
First Posted: February 3, 2011
Results First Submitted: February 17, 2013
Results First Posted: March 22, 2013
Last Update Posted: March 22, 2013