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

History of Changes

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

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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
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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

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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 ]

Show Outcome Measure 1

2. Primary:

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

Show Outcome Measure 2

3. Secondary:

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

Show Outcome Measure 3

4. Secondary:

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

Show Outcome Measure 4

5. Secondary:

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

Show Outcome Measure 5

6. Secondary:

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

Show Outcome Measure 6

7. Secondary:

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

Show Outcome Measure 7

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 ]

Show Outcome Measure 8

9. Other Pre-specified:

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

Show Outcome Measure 9

10. Other Pre-specified:

Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort [ Time Frame: Baseline ]

Show Outcome Measure 10

11. Other Pre-specified:

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

Show Outcome Measure 11

12. Other Pre-specified:

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

Show Outcome Measure 12

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. ]

Show Outcome Measure 13

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. ]

Show Outcome Measure 14

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 ]

Show Outcome Measure 15

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 ]

Show Outcome Measure 16

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 ]

Show Outcome Measure 17

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 ]

Show Outcome Measure 18

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 ]

Show Outcome Measure 19

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 ]

Show Outcome Measure 20

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 ]

Show Outcome Measure 21

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 ]

Show Outcome Measure 22

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 ]

Show Outcome Measure 23

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 ]

Show Outcome Measure 24

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 ]

Show Outcome Measure 25

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 ]

Show Outcome Measure 26

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 ]

Show Outcome Measure 27

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 ]

Show Outcome Measure 28

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. ]

Hide Outcome Measure 29

Measure Type	Other Pre-specified
Measure Title	Overall Summary of Adverse Events During ST+LT Treatment Period - Open-Label Cohort
Measure Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related events=relationship of certain, probable, possible, or missing.
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.
Safety Issue	Yes

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.
All treated participants

Reporting Groups

	Description
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).

Measured Values

	Open-Label Treatment Cohort (Direct Enrollees)
Number of Participants Analyzed [units: participants]	66
Overall Summary of Adverse Events During ST+LT Treatment Period - Open-Label Cohort [units: participants]
At Least 1 AE	49
At Least 1 Related AE	9
Deaths	0
At Least 1 SAE	6
At Least 1 Related SAE	0
Discontinuations Due to SAEs	2
Discontinuations Due to AEs	5

No statistical analysis provided for Overall Summary of Adverse Events During ST+LT Treatment Period - Open-Label Cohort

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. ]

Show Outcome Measure 30

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. ]

Show Outcome Measure 31

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. ]

Show Outcome Measure 32

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. ]

Show Outcome Measure 33

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. ]

Show Outcome Measure 34

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 ]

Show Outcome Measure 35

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 ]

Show Outcome Measure 36

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 ]

Show Outcome Measure 37

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 ]

Show Outcome Measure 38

Serious Adverse Events

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Other Adverse Events

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More Information

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

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:

Rosenstock J, Aguilar-Salinas C, Klein E, Nepal S, List J, Chen R; CV181-011 Study Investigators. Effect of saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes. Curr Med Res Opin. 2009 Oct;25(10):2401-11.

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

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