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Efficacy and Safety of Alogliptin in Participants With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01289119
First received: February 1, 2011
Last updated: February 17, 2013
Last verified: February 2013
Results First Received: February 17, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Alogliptin
Drug: Placebo to alogliptin
Drug: Metformin
Drug: Pioglitazone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants took part in the study at 30 investigative sites in China, Taiwan province and Hong Kong from 23 December 2010 to 19 December 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Placebo Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Alogliptin Monotherapy Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Metformin 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.
Metformin + Alogliptin Add-on Therapy 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.
Pioglitazone 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.
Pioglitazone + Alogliptin Add-on Therapy 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.

Participant Flow:   Overall Study
    Placebo     Alogliptin Monotherapy     Metformin     Metformin + Alogliptin Add-on Therapy     Pioglitazone     Pioglitazone + Alogliptin Add-on Therapy  
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  
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.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Alogliptin Monotherapy Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Metformin 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.
Metformin + Alogliptin Add-on Therapy 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.
Pioglitazone 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.
Pioglitazone + Alogliptin Add-on Therapy 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 Total of all reporting groups

Baseline Measures
    Placebo     Alogliptin Monotherapy     Metformin     Metformin + Alogliptin Add-on Therapy     Pioglitazone     Pioglitazone + Alogliptin Add-on Therapy     Total  
Number of Participants  
[units: participants]
  93     92     98     99     63     61     506  
Age  
[units: years]
Mean ± Standard Deviation
  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  
[units: participants]
             
<65 Years     81     80     86     85     56     52     440  
≥65 years     12     12     12     14     7     9     66  
Gender  
[units: participants]
             
Female     39     37     50     48     24     33     231  
Male     54     55     48     51     39     28     275  
Race/Ethnicity, Customized  
[units: participants]
  93     92     98     99     63     61     506  
Region of Enrollment  
[units: 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  
[units: cm]
Mean ± Standard Deviation
  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  
[units: kg]
Mean ± Standard Deviation
  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)  
[units: kg/m^2]
Mean ± Standard Deviation
  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  
[units: years]
Mean ± Standard Deviation
  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  
[units: 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]
[units: mg]
Mean ± Standard Deviation
  NA  ± NA [2]   NA  ± NA [2]   1484.2  ± 451.09     1472.2  ± 417.31     1355.0  ± 431.80     1295.0  ± 506.82     1426.6  ± 450.90  
Stable Daily Dose of Pioglitazone [3]
[units: mg]
Mean ± Standard Deviation
  NA  ± NA [4]   NA  ± NA [4]   NA  ± NA [4]   NA  ± NA [4]   21.9  ± 11.37     20.2  ± 7.19     21.0  ± 9.55  
[1] 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
[3] Participant population for this measure for each treatment arm: 0, 0, 0, 0, 63, 61; Total population: 124
[4] Participants in this arm were not taking Pioglitazone



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Glycosylated Hemoglobin (HbA1c)   [ Time Frame: Baseline and Week 16. ]
  Hide Outcome Measure 1

Measure Type Primary
Measure Title Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Measure 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.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The 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.

Reporting Groups
  Description
Placebo Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks
Alogliptin Monotherapy Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
Metformin 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.
Metformin + Alogliptin Add-on Therapy 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.
Pioglitazone 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.
Pioglitazone + Alogliptin Add-on Therapy 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.

Measured Values
    Placebo     Alogliptin Monotherapy     Metformin     Metformin + Alogliptin Add-on Therapy     Pioglitazone     Pioglitazone + Alogliptin Add-on Therapy  
Number of Participants Analyzed  
[units: participants]
  90     90     97     98     63     60  
Change From Baseline in Glycosylated Hemoglobin (HbA1c)  
[units: percentage¬†glycosylated¬†hemoglobin]
Least Squares Mean ± Standard Error
  -0.42  ± 0.074     -0.99  ± 0.074     -0.22  ± 0.065     -0.91  ± 0.065     -0.25  ± 0.097     -0.76  ± 0.101  


Statistical Analysis 1 for Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Groups [1] Placebo vs. Alogliptin Monotherapy
Method [2] ANCOVA
P Value [3] <0.001
LS Mean Difference [4] -0.58
95% Confidence Interval ( -0.78 to -0.37 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was conducted at the 2-sided 5% significance level without a multiplicity adjustment.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  ANCOVA model with treatment as a fixed effect, and baseline HbA1c as a covariate.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Groups [1] Metformin vs. Metformin + Alogliptin Add-on Therapy
Method [2] ANCOVA
P Value [3] <0.001
LS Mean Difference [4] -0.69
95% Confidence Interval ( -0.87 to -0.51 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was conducted at the 2-sided 5% significance level without a multiplicity adjustment.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  ANCOVA model with treatment as a fixed effect, and baseline HbA1c with baseline metformin dose as covariates.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Groups [1] Pioglitazone vs. Pioglitazone + Alogliptin Add-on Therapy
Method [2] ANCOVA
P Value [3] <0.001
LS Mean Difference [4] -0.52
95% Confidence Interval ( -0.75 to -0.28 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was conducted at the 2-sided 5% significance level without a multiplicity adjustment.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  ANCOVA model with treatment as a fixed effect, and baseline HbA1c with baseline metformin therapy status and baseline pioglitazone dose as covariates.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Change From Baseline in HbA1c Over Time   [ Time Frame: Baseline and Weeks 4, 8 and 12. ]

3.  Secondary:   Change From Baseline in Fasting Plasma Glucose Over Time   [ Time Frame: Baseline and Weeks 4, 8, 12 and 16. ]

4.  Secondary:   Percentage of Participants With Marked Hyperglycemia   [ Time Frame: Randomization to Week 16. ]

5.  Secondary:   Change From Baseline in Body Weight   [ Time Frame: Baseline and Weeks 8 and 16. ]

6.  Secondary:   Percentage of Participants With HbA1c ≤6.5% at Week 16   [ Time Frame: Week 16 ]

7.  Secondary:   Percentage of Participants With HbA1c ≤7.0% at Week 16   [ Time Frame: Week 16 ]

8.  Secondary:   Percentage of Participants With HbA1c ≤7.5% at Week 16   [ Time Frame: Week 16 ]

9.  Secondary:   Percentage of Participants With a Decrease in HbA1c ≥ 0.5%   [ Time Frame: Baseline and Week 16 ]

10.  Secondary:   Percentage of Participants With a Decrease in HbA1c ≥1.0%   [ Time Frame: Baseline and Week 16 ]

11.  Secondary:   Percentage of Participants With a Decrease in HbA1c ≥1.5%   [ Time Frame: Baseline and Week 16. ]

12.  Secondary:   Percentage of Participants With a Decrease in HbA1c ≥2.0%   [ Time Frame: Baseline and Week 16. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information