Saxagliptin Treatment in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00121641
First received: July 15, 2005
Last updated: August 5, 2011
Last verified: August 2011
Results First Received: April 12, 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
Drug: Placebo matching Saxagliptin
Drug: Metformin
Drug: Placebo matching Metformin

  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
1035 subjects were enrolled; 422 entered the 2-week dietary/exercise placebo lead-in. 21 did not enter double-blind treatment period (19 discontinued, 2 randomized but did not receive study drug). 68 with screening hemoglobin A1c (A1C) >10.0% and ≤12.0% entered directly in the open-label cohort; 66 received at least 1 dose of saxagliptin 10mg.

Reporting Groups
  Description
Saxagliptin 2.5 mg Tablets, Oral, 2.5 mg, Once daily (24 weeks short term [ST], 42 months long term [LT]); Metformin 500-2000 mg (as needed for rescue).
Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).
Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).
Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Open-Label Treatment Cohort (Direct Enrollees) Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).

Participant Flow for 2 periods

Period 1:   24-week Short-term Treatment Period
    Saxagliptin 2.5 mg     Saxagliptin 5 mg     Saxagliptin 10 mg     Placebo     Open-Label Treatment Cohort (Direct Enrollees)  
STARTED     102     106     98     95     66  
COMPLETED     73     68     69     55     25  
NOT COMPLETED     29     38     29     40     41  
Lack of Efficacy                 15                 21                 14                 25                 30  
Subject Withdrew Consent                 9                 11                 5                 10                 3  
Adverse Event                 3                 3                 4                 0                 2  
Lost to Follow-up                 0                 2                 3                 4                 4  
Poor / Non-compliance                 0                 0                 3                 1                 1  
Subject No Longer Meets Study Criteria                 1                 1                 0                 0                 1  
Other Reason                 1                 0                 0                 0                 0  

Period 2:   48-month Short Term + Long Term Period
    Saxagliptin 2.5 mg     Saxagliptin 5 mg     Saxagliptin 10 mg     Placebo     Open-Label Treatment Cohort (Direct Enrollees)  
STARTED     102     106     98     95     66  
COMPLETED     23     24     28     24     8  
NOT COMPLETED     79     82     70     71     58  
Lack of Efficacy                 26                 27                 21                 26                 25  
Subject Withdrew Consent                 25                 28                 17                 24                 10  
Adverse Event                 9                 10                 10                 5                 5  
Lost to Follow-up                 9                 7                 12                 11                 12  
Poor / Non-compliance                 4                 1                 4                 2                 2  
Subject No Longer Meets Study Criteria                 1                 3                 2                 1                 2  
Pregnancy                 0                 1                 0                 1                 0  
Administrative Reason by Sponsor                 0                 2                 1                 0                 1  
Death                 0                 0                 0                 1                 0  
Missing                 0                 0                 1                 0                 0  
Other Reason                 5                 3                 2                 0                 1  



  Baseline Characteristics
  Hide Baseline Characteristics

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
Saxagliptin 2.5 mg Tablets, Oral, 2.5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).
Saxagliptin 5 mg Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).
Saxagliptin 10 mg Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue).
Placebo Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT); Metformin 500-2000 mg (as needed for rescue)
Total Total of all reporting groups

Baseline Measures
    Saxagliptin 2.5 mg     Saxagliptin 5 mg     Saxagliptin 10 mg     Placebo     Total  
Number of Participants  
[units: participants]
  102     106     98     95     401  
Age  
[units: years]
Mean ± Standard Deviation
  53.27  ± 10.06     53.91  ± 11.57     52.73  ± 11.27     53.91  ± 12.32     53.46  ± 11.29  
Age, Customized  
[units: participants]
         
<65 years     91     86     84     77     338  
>= 65 years     11     20     14     18     63  
>=75 years     2     1     1     2     6  
Gender  
[units: participants]
         
Female     44     52     53     48     197  
Male     58     54     45     47     204  
Race/Ethnicity, Customized  
[units: participants]
         
White     89     93     80     79     341  
Black/African American     5     5     6     6     22  
Asian     5     4     6     3     18  
Other     3     4     6     7     20  
Not Reported     0     0     0     0     0  
Race/Ethnicity, Customized  
[units: Partcipants]
         
Hispanic / Latino     16     14     14     15     59  
Not Hispanic / Latino     45     49     42     38     174  
Not Reported     41     43     42     42     168  
Age Categorization, Female Only  
[units: Participants]
         
=< 50 years     17     24     22     19     82  
> 50 years     27     28     31     29     115  
Weight  
[units: kg]
Mean ± Standard Deviation
  92.10  ± 18.39     91.09  ± 18.53     89.30  ± 17.67     86.56  ± 16.90     89.84  ± 17.96  
Body Mass Index  
[units: kg/m^2]
Mean ± Standard Deviation
  31.90  ± 4.82     32.30  ± 4.53     31.71  ± 4.71     30.93  ± 4.26     31.73  ± 4.60  
Body Mass Index Categorization  
[units: Participants]
         
< 30     36     40     35     42     153  
>= 30     66     66     63     53     248  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Hemoglobin A1c (A1C) Changes From Baseline at Week 24   [ Time Frame: Baseline, Week 24 ]

2.  Primary:   A1C Changes From Baseline at Week 24 - Open Label Cohort   [ Time Frame: Baseline, Week 24 ]

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

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

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

6.  Secondary:   Baseline and Change From Baseline at Week 24 in Fasting Plasma Glucose (FPG) - Open Label Cohort   [ Time Frame: Baseline, Week 24 ]

7.  Secondary:   Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24 - Open Label Cohort   [ Time Frame: Week 24 ]

8.  Secondary:   Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC) - Open Label Cohort   [ Time Frame: Baseline, Week 24 ]

9.  Other Pre-specified:   Baseline Demographic Characteristic (Age, Continuous) - Summary for ST + LT Treatment Period - Open-Label Cohort   [ Time Frame: Baseline ]

10.  Other Pre-specified:   Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort   [ Time Frame: Baseline ]

11.  Other Pre-specified:   Baseline Demographic Characteristic (Weight) - Summary for ST + LT Treatment Period - Open-Label Cohort   [ Time Frame: Baseline ]

12.  Other Pre-specified:   Baseline Demographic Characteristic (Body Mass Index) - Summary for ST + LT Treatment Period - Open-Label Cohort   [ Time Frame: Baseline ]

13.  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; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 109 weeks in 10 mg arm, 94.7 weeks in 2.5 mg arm, 103 weeks in 5 mg arm, and 98.4 weeks in placebo arm. ]

14.  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 was 109 weeks in 10 mg arm, 94.7 weeks in 2.5 mg arm, 103 weeks in 5 mg arm, and 98.4 weeks in placebo arm. ]

15.  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 ]

16.  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 ]

17.  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 ]

18.  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 ]

19.  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 ]

20.  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 ]

21.  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 ]

22.  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 ]

23.  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 ]

24.  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 ]

25.  Other Pre-specified:   Changes From Baseline in Systolic Blood Pressure During the ST + LT Period   [ Time Frame: Baseline, 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 ]

26.  Other Pre-specified:   Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period   [ Time Frame: Baseline, 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 ]

27.  Other Pre-specified:   Changes From Baseline in Heart Rate During the ST + LT Period   [ Time Frame: Baseline, 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 ]

28.  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 ]

29.  Other Pre-specified:   Overall Summary of Adverse Events During ST+LT Treatment Period - Open-Label Cohort   [ Time Frame: AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 34 weeks. ]

30.  Other Pre-specified:   Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort   [ 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 was 34 weeks. ]

31.  Other Pre-specified:   All Reported Hypoglycemic Adverse Events During ST + LT Treatment Period   [ Time Frame: AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 109 weeks in 10 mg arm, 94.7 weeks in 2.5 mg arm, 103 weeks in 5 mg arm, and 98.4 weeks in placebo arm. ]

32.  Other Pre-specified:   Confirmed Hypoglycemia During ST + LT Treatment Period   [ Time Frame: AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 109 weeks in 10 mg arm, 94.7 weeks in 2.5 mg arm, 103 weeks in 5 mg arm, and 98.4 weeks in placebo arm. ]

33.  Other Pre-specified:   All Reported Hypoglycemic Adverse Events During ST + LT Treatment Period - Open-Label Cohort   [ Time Frame: AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 34 weeks. ]

34.  Other Pre-specified:   Confirmed Hypoglycemia During ST + LT Treatment Period - Open-Label Cohort   [ Time Frame: AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 34 weeks. ]

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

36.  Other Pre-specified:   Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort   [ Time Frame: Baseline, 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 ]

37.  Other Pre-specified:   Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort   [ Time Frame: Baseline, 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 ]

38.  Other Pre-specified:   Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort   [ Time Frame: Baseline, 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 ]


  Serious Adverse Events


  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: NCT00121641     History of Changes
Other Study ID Numbers: CV181-011
Study First Received: July 15, 2005
Results First Received: April 12, 2011
Last Updated: August 5, 2011
Health Authority: United States: Food and Drug Administration