Text Size

Study Assessing Saxagliptin Treatment In Type 2 Diabetic Subjects Who Are Not Controlled With Metformin Alone

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00121667
First received: July 18, 2005
Last updated: August 5, 2011
Last verified: August 2011
History of Changes
Results First Received: March 15, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Saxagliptin + Metformin
Drug: Placebo + Metformin
Drug: Pioglitazone

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
1462 participants were enrolled, and 787 entered the lead-in period. 45 discontinued the during the lead-in period. 19 subjects no longer met study criteria, 10 subjects withdrew consent, and 2 subjects were randomized but not treated.

Reporting Groups
  Description
Saxagliptin 2.5 mg + Metformin Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Saxagliptin 5 mg + Metformin Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Saxagliptin 10 mg + Metformin Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Placebo+ Metformin Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).

Participant Flow for 2 periods

 Period 1:   Short Term (ST) Period
    Saxagliptin 2.5 mg + Metformin     Saxagliptin 5 mg + Metformin     Saxagliptin 10 mg + Metformin     Placebo+ Metformin  
STARTED     192     191     181     179  
COMPLETED     148     143     140     112  
NOT COMPLETED     44     48     41     67  
Lack of Efficacy                 25                 22                 27                 44  
Subject Withdrew Consent                 8                 13                 4                 11  
Adverse Event                 5                 6                 5                 3  
Lost to Follow-up                 3                 4                 4                 3  
Poor / Non-compliance                 0                 1                 1                 2  
Subject No Longer Meets Study Criteria                 0                 2                 0                 2  
Other Reason                 3                 0                 0                 0  
Death                 0                 0                 0                 1  
Pregnancy                 0                 0                 0                 1  

Period 2:   Short Term (ST) + Long Term (LT) Period
    Saxagliptin 2.5 mg + Metformin     Saxagliptin 5 mg + Metformin     Saxagliptin 10 mg + Metformin     Placebo+ Metformin  
STARTED     192     191     181     179  
Completed Study Without Being Rescued     14     18     23     7  
COMPLETED     64     58     68     39  
NOT COMPLETED     128     133     113     140  
Lack of Efficacy                 54                 51                 42                 65  
Subject Withdrew Consent                 38                 34                 26                 30  
Adverse Event                 12                 18                 13                 10  
Lost to Follow-up                 11                 11                 13                 16  
Other Reason                 5                 7                 6                 3  
Subject No Longer Meets Study Criteria                 3                 6                 5                 9  
Poor / Non-compliance                 3                 5                 8                 4  
Pregnancy                 1                 1                 0                 1  
Death                 1                 0                 0                 2  



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
Saxagliptin 2.5 mg + Metformin Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Saxagliptin 5 mg + Metformin Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Saxagliptin 10 mg + Metformin Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Placebo+ Metformin Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Total Total of all reporting groups

Baseline Measures
    Saxagliptin 2.5 mg + Metformin     Saxagliptin 5 mg + Metformin     Saxagliptin 10 mg + Metformin     Placebo+ Metformin     Total  
Number of Participants  
[units: participants]
 		  192     191     181     179     743  
Age  
[units: years]
Mean ± Standard Deviation 		  54.66  ± 10.08     54.69  ± 9.62     54.18  ± 10.14     54.76  ± 10.18     54.57  ± 9.98  
Age, Customized  
[units: participants]
 		         
< 65 years     159     159     155     153     626  
>= 65 years     33     32     26     26     117  
>= 75 years     3     2     5     3     13  
Gender  
[units: participants]
 		         
Female     109     88     86     83     366  
Male     83     103     95     96     377  
Race/Ethnicity, Customized  
[units: participants]
 		         
White     153     159     144     150     606  
Black / African American     8     11     14     7     40  
Asian     8     3     5     4     20  
Other     23     18     18     18     77  
Race/Ethnicity, Customized  
[units: participants]
 		         
Hispanic / Latino     27     25     29     27     108  
Not Hispanic / Latino     64     62     54     49     229  
Not Reported     101     104     98     103     406  
Age Characterization Female Only  
[units: participants]
 		         
=< 50 years     33     34     24     21     112  
> 50 years     76     54     62     62     254  
Weight  
[units: kg]
Mean ± Standard Deviation 		  85.97  ± 17.57     87.26  ± 17.04     87.83  ± 18.90     87.14  ± 17.75     87.04  ± 17.79  
Body Mass Index  
[units: kg/m^2]
Mean ± Standard Deviation 		  31.68  ± 5.15     31.23  ± 4.67     31.12  ± 4.79     31.57  ± 4.80     31.40  ± 4.85  
Body Mass Index Categorization  
[units: Participants]
 		         
< 30     75     84     82     76     317  
>= 30     117     107     99     103     426  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Baseline and Change From Baseline in Hemoglobin A1c (A1C) at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 1

2.  Secondary:   Baseline and Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24   [ Time Frame: Baseline, Week 24 ]
  Show Outcome Measure 2

3.  Secondary:   Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24   [ Time Frame: Week 24 ]
  Show Outcome Measure 3

4.  Secondary:   Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC)   [ Time Frame: Baseline, Week 24 ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC)
Measure Description Mean change from baseline is adjusted for baseline value.
Time Frame Baseline, Week 24  
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.
Randomized Participants with measurement at timepoint. Last Observation Carried Forward (LOCF).

Reporting Groups
  Description
Saxagliptin 2.5 mg + Metformin Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Saxagliptin 5 mg + Metformin Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Saxagliptin 10 mg + Metformin Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).
Placebo+ Metformin Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT); Pioglitazone 15-45 mg (as needed for rescue).

Measured Values
    Saxagliptin 2.5 mg + Metformin     Saxagliptin 5 mg + Metformin     Saxagliptin 10 mg + Metformin     Placebo+ Metformin  
Number of Participants Analyzed  
[units: participants]
 		  150     146     148     131  
Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC)  
[units: mg*min/dL]
Mean ± Standard Error 		       
Baseline Mean     48224  ± 869.70     49021  ± 876.17     44931  ± 889.85     47407  ± 1071.9  
Adjusted Mean Change from Baseline     -8891  ± 797.97     -9586  ± 810.46     -8137  ± 807.88     -3291  ± 853.24  


Statistical Analysis 1 for Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC)
Groups [1] Saxagliptin 2.5 mg + Metformin vs. Placebo+ Metformin
Method [2] ANCOVA
P Value [3] <.0001
Mean Difference (Final Values) [4] -5599
Standard Error of the mean ± 1168.2
95% Confidence Interval ( -7894 to -3305 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  Adjusted mean difference for saxagliptin groups vs placebo in Week 24 (LOCF). Adjusted for baseline.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Significance testing based on hierarchical testing. Primary and secondary endpoints are presented in order of testing.
[4] Other relevant estimation information:
  ANCOVA model: difference between week t and baseline values = baseline values + treatment

Statistical Analysis 2 for Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC)
Groups [1] Saxagliptin 5 mg + Metformin vs. Placebo+ Metformin
Method [2] ANCOVA
P Value [3] <.0001
Mean Difference (Final Values) [4] -6294
Standard Error of the mean ± 1176.8
95% Confidence Interval ( -8606 to -3983 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  Adjusted mean difference for saxagliptin groups vs placebo in Week 24 (LOCF). Adjusted for baseline.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Significance testing based on hierarchical testing. Primary and secondary endpoints are presented in order of testing.
[4] Other relevant estimation information:
  ANCOVA model: difference between week t and baseline values = baseline values + treatment

Statistical Analysis 3 for Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC)
Groups [1] Saxagliptin 10 mg + Metformin vs. Placebo+ Metformin
Method [2] ANCOVA
P Value [3] <.0001
Mean Difference (Final Values) [4] -4845
Standard Error of the mean ± 1175.1
95% Confidence Interval ( -7153 to -2537 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant information, such as adjustments or degrees of freedom:
  Adjusted mean difference for saxagliptin groups vs placebo in Week 24 (LOCF). Adjusted for baseline.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Significance testing based on hierarchical testing. Primary and secondary endpoints are presented in order of testing.
[4] Other relevant estimation information:
  ANCOVA model: difference between week t and baseline values = baseline values + treatment



5.  Other Pre-specified:   Overall Summary of Adverse Events During ST+LT Treatment Period   [ Time Frame: AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla ]
  Show Outcome Measure 5

6.  Other Pre-specified:   Marked Laboratory Abnormalities - During ST + LT Treatment Period   [ Time Frame: Lab assessments taken during and up to 14 days after the last dose of study drug during the ST + LT Treatment Period. Mean duration of exposure: 124, 118, 130, 95 weeks, respectively, for 2.5mg, 5mg, 10 mg, placebo. ]
  Show Outcome Measure 6

7.  Other Pre-specified:   Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period   [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 7

8.  Other Pre-specified:   Baseline and Changes From Baseline in Hematocrit During the ST + LT Period   [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 8

9.  Other Pre-specified:   Baseline and Changes From Baseline in Red Blood Cell Counts (x 10^6 c/µL) During the ST + LT Period   [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 9

10.  Other Pre-specified:   Baseline and Changes From Baseline in Platelet Counts (x 10^9 c/L) During the ST + LT Period   [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 10

11.  Other Pre-specified:   Baseline and Changes From Baseline in White Blood Cell Counts (x 10^3 c/µL) During the ST + LT Period   [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 11

12.  Other Pre-specified:   Baseline and Changes From Baseline in Absolute Neutrophil Counts (x 10^3 c/µL) During the ST + LT Period   [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 12

13.  Other Pre-specified:   Baseline and Changes From Baseline in Absolute Lymphocyte Counts (x 10^3 c/µL) During the ST + LT Period   [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 13

14.  Other Pre-specified:   Baseline and Changes From Baseline in Absolute Monocyte Counts (x 10^3 c/µL) During the ST + LT Period   [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 14

15.  Other Pre-specified:   Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period   [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 15

16.  Other Pre-specified:   Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period   [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 16

17.  Other Pre-specified:   Changes From Baseline in Systolic Blood Pressure During the ST + LT Period   [ Time Frame: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 17

18.  Other Pre-specified:   Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period   [ Time Frame: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 18

19.  Other Pre-specified:   Changes From Baseline in Heart Rate During the ST + LT Period   [ Time Frame: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206 ]
  Show Outcome Measure 19

20.  Other Pre-specified:   Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period   [ Time Frame: Baseline, Weeks 12, 24, 76, 102, 154, 206, ]
  Show Outcome Measure 20

21.  Other Pre-specified:   All Reported Hypoglycemic Adverse Events During the ST + LT Treatment Period   [ Time Frame: AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla ]
  Show Outcome Measure 21

22.  Other Pre-specified:   Confirmed Hypoglycemia During the ST + LT Treatment Period   [ Time Frame: AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla ]
  Show Outcome Measure 22


  Serious Adverse Events
  Show Serious Adverse Events


  Other Adverse Events
  Show Other Adverse Events


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


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


Results Point of Contact:  
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


Publications:

Publications automatically indexed to this study:


Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00121667     History of Changes
Other Study ID Numbers: CV181-014
Study First Received: July 18, 2005
Results First Received: March 15, 2011
Last Updated: August 5, 2011
Health Authority: United States: Food and Drug Administration