Study of Multiple Doses of Saxagliptin (BMS-477118)

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
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Reporting Groups

	Description
Saxagliptin 2.5 mg (0-40 mg Cohort)	The Saxagliptin 2.5 mg group includes data from subjects randomized to receive blinded Saxagliptin 2.5 mg for 12 weeks
Saxagliptin 5 mg (0-40 mg Cohort)	The Saxagliptin 5 mg group includes data from subjects randomized to receive blinded Saxagliptin 5 mg for 12 weeks.
Saxagliptin 10 mg (0-40 mg Cohort)	The Saxagliptin 10 mg group includes data from subjects randomized to receive blinded Saxagliptin 10 mg for 12 weeks.
Saxagliptin 20 mg (0-40 mg Cohort)	The Saxagliptin 20 mg group includes data from subjects randomized to receive blinded Saxagliptin 20 mg for 12 weeks.
Saxagliptin 40 mg (0-40 mg Cohort)	The Saxagliptin 40 mg group includes data from subjects randomized to receive blinded Saxagliptin 40 mg for 12 weeks.
Placebo (0-40 mg Cohort)	The placebo group includes data from subjects randomized to receive blinded placebo for 12 weeks.
Saxagliptin 100 mg (0 & 100 mg Cohort)	The Saxagliptin 100 mg group includes data from subjects randomized to receive blinded Saxagliptin 100 mg for 6 weeks.
Placebo (0 & 100 mg Cohort)	The placebo group includes data from subjects randomized to receive blinded placebo for 6 weeks.
Saxa 0-40 mg Cohort (Follow-up Period)	The follow-up period is 4 weeks and includes: subjects completing 12 weeks of double-blind dosing (received single blind placebo); subjects who met the hyperglycemic rescue criteria (received open-label metformin in addition to placebo); subjects meeting hyperglycemic discontinuation criteria (received open-label metformin); and subjects who discontinued the double-blind period for reasons other than hyperglycemia (received metformin only if clinically indicated). Open-label metformin was (initiated at 500 mg per day and titrated in 500 mg increments after 2 weeks or as clinically indicated). Additional or alternative antihyperglycemic agents were permitted during the follow-up period as clinically indicated.
Saxa 0 & 100 mg Cohort (Follow-up Period)	The follow-up period is 4 weeks and includes: subjects completing 6 weeks of double-blind dosing (received single blind placebo); subjects who met the hyperglycemic rescue criteria (received open-label metformin in addition to placebo); subjects meeting hyperglycemic discontinuation criteria (received open-label metformin); and subjects who discontinued the double-blind period for reasons other than hyperglycemia (received metformin only if clinically indicated). Open-label metformin was (initiated at 500 mg per day and titrated in 500 mg increments after 2 weeks or as clinically indicated). Additional or alternative antihyperglycemic agents were permitted during the follow-up period as clinically indicated.

Participant Flow for 2 periods

Period 1:   Double-Blind Treatment Period

	Saxagliptin 2.5 mg (0-40 mg Cohort)	Saxagliptin 5 mg (0-40 mg Cohort)	Saxagliptin 10 mg (0-40 mg Cohort)	Saxagliptin 20 mg (0-40 mg Cohort)	Saxagliptin 40 mg (0-40 mg Cohort)	Placebo (0-40 mg Cohort)	Saxagliptin 100 mg (0 & 100 mg Cohort)	Placebo (0 & 100 mg Cohort)	Saxa 0-40 mg Cohort (Follow-up Period)	Saxa 0 & 100 mg Cohort (Follow-up Period)
STARTED	55	47	63	54	52	67	44	41	0	0
COMPLETED	48 [1]	37 [1]	54 [1]	43 [1]	45 [1]	55 [1]	44 [1]	35 [1]	0	0
NOT COMPLETED	7	10	9	11	7	12	0	6	0	0
Administrative reason by sponsor	0	0	0	1	0	0	0	0	0	0
Adverse Event	0	1	1	1	1	1	0	0	0	0
Lack of Efficacy	2	5	5	7	3	6	0	1	0	0
Lost to Follow-up	0	0	0	1	1	2	0	1	0	0
Poor/Noncompliance	1	1	0	0	0	0	0	1	0	0
Subject no longer meets study criteria	0	0	0	0	1	1	0	0	0	0
Subject Withdrew consent	4	3	3	1	1	2	0	3	0	0

Period 2:   Follow-Up Period

	Saxagliptin 2.5 mg (0-40 mg Cohort)	Saxagliptin 5 mg (0-40 mg Cohort)	Saxagliptin 10 mg (0-40 mg Cohort)	Saxagliptin 20 mg (0-40 mg Cohort)	Saxagliptin 40 mg (0-40 mg Cohort)	Placebo (0-40 mg Cohort)	Saxagliptin 100 mg (0 & 100 mg Cohort)	Placebo (0 & 100 mg Cohort)	Saxa 0-40 mg Cohort (Follow-up Period)	Saxa 0 & 100 mg Cohort (Follow-up Period)
STARTED	0	0	0	0	0	0	0	0	309 [1]	80 [1]
COMPLETED	0	0	0	0	0	0	0	0	296	78
NOT COMPLETED	0	0	0	0	0	0	0	0	13	2
Adverse Event	0	0	0	0	0	0	0	0	1	0
Lack of Efficacy	0	0	0	0	0	0	0	0	3	0
Lost to Follow-up	0	0	0	0	0	0	0	0	5	1
Physician Decision	0	0	0	0	0	0	0	0	1	0
Poor/Noncompliance	0	0	0	0	0	0	0	0	1	0
Subject withdrew Consent	0	0	0	0	0	0	0	0	2	1

Reporting Groups

	Description
Saxagliptin 2.5 mg (0-40 mg Cohort)	No text entered.
Saxagliptin 5 mg (0-40 mg Cohort)	No text entered.
Saxagliptin 10 mg (0-40 mg Cohort)	No text entered.
Saxagliptin 20 mg (0-40 mg Cohort)	No text entered.
Saxagliptin 40 mg (0-40 mg Cohort)	No text entered.
Placebo (0-40 mg Cohort)	No text entered.
Saxagliptin 100 mg (0 & 100 mg Cohort)	No text entered.
Placebo (0 & 100 mg Cohort)	No text entered.
Total	Total of all reporting groups

Baseline Measures

	Saxagliptin 2.5 mg (0-40 mg Cohort)	Saxagliptin 5 mg (0-40 mg Cohort)	Saxagliptin 10 mg (0-40 mg Cohort)	Saxagliptin 20 mg (0-40 mg Cohort)	Saxagliptin 40 mg (0-40 mg Cohort)	Placebo (0-40 mg Cohort)	Saxagliptin 100 mg (0 & 100 mg Cohort)	Placebo (0 & 100 mg Cohort)	Total
Number of Participants   [units: participants]	55	47	63	54	52	67	44	41	423
Age, Customized   [units: participants]
<65 years	50	39	54	50	41	55	38	35	362
>= 65 years	5	8	9	4	11	12	6	6	61
Gender   [units: participants]
Female	33	22	23	16	22	25	17	18	176
Male	22	25	40	38	30	42	27	23	247

1.  Primary:

Analysis of Test for Positive Efficacy Trend in Change From Baseline in Hemoglobin A1c (A1C) at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

2.  Primary:

Change From Baseline in A1C at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

3.  Secondary:

Change From Baseline in A1C at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

4.  Secondary:

Change From Baseline in Fasting Serum Glucose (FSG) at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

5.  Secondary:

Change From Baseline in FSG at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

6.  Secondary:

Change From Baseline in Fructosamine at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

7.  Secondary:

Change From Baseline in Fructosamine at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

8.  Secondary:

Change From Baseline in Insulin at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

9.  Secondary:

Change From Baseline in Insulin at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

10.  Secondary:

Change From Baseline in C-peptide at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

11.  Secondary:

Change From Baseline in C-peptide at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

12.  Secondary:

Change From Baseline in Postprandial Glucose 0-60 Minute Area Under the Curve (AUC) at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

13.  Secondary:

Change From Baseline in Postprandial Glucose 0-60 Minute AUC at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

14.  Secondary:

Change From Baseline in Postprandial Insulin 0-60 Minute AUC at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

15.  Secondary:

Change From Baseline in Postprandial Insulin 0-60 Minute AUC at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

16.  Secondary:

Change From Baseline in Postprandial C-peptide 0-60 Minute AUC at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

17.  Secondary:

Change From Baseline in Postprandial C-peptide 0-60 Minute AUC at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

18.  Secondary:

Change From Baseline in 15-minute Postprandial Glucose at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

19.  Secondary:

Change From Baseline in 30-minute Postprandial Glucose at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

20.  Secondary:

Change From Baseline in 60-minute Postprandial Glucose at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

21.  Secondary:

Change From Baseline in 15-minute Postprandial Glucose at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

22.  Secondary:

Change From Baseline in 30-minute Postprandial Glucose at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

23.  Secondary:

Change From Baseline in 60-minute Postprandial Glucose at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

24.  Secondary:

Change From Baseline in 15-minute Postprandial Insulin at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

25.  Secondary:

Change From Baseline in 30-minute Postprandial Insulin at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

26.  Secondary:

Change From Baseline in 60-minute Postprandial Insulin at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

27.  Secondary:

Change From Baseline in 15-minute Postprandial Insulin at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

28.  Secondary:

Change From Baseline in 30-minute Postprandial Insulin at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

29.  Secondary:

Change From Baseline in 60-minute Postprandial Insulin at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

30.  Secondary:

Change From Baseline in 15-minute Postprandial C-peptide at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

31.  Secondary:

Change From Baseline in 30-minute Postprandial C-peptide at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

32.  Secondary:

Change From Baseline in 60-minute Postprandial C-peptide at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

33.  Secondary:

Change From Baseline in 15-minute Postprandial C-peptide at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

34.  Secondary:

Change From Baseline in 30-minute Postprandial C-peptide at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

35.  Secondary:

Change From Baseline in 60-minute Postprandial C-peptide at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

36.  Secondary:

Change From Baseline in 15-minute Postprandial Glucose Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

37.  Secondary:

Change From Baseline in 30-minute Postprandial Glucose Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

38.  Secondary:

Change From Baseline in 60-minute Postprandial Glucose Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

39.  Secondary:

Change From Baseline in 15-minute Postprandial Glucose Excursion at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

40.  Secondary:

Change From Baseline in 30-minute Postprandial Glucose Excursion at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

41.  Secondary:

Change From Baseline in 60-minute Postprandial Glucose Excursion at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

42.  Secondary:

Change From Baseline in 15-minute Postprandial Insulin Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

43.  Secondary:

Change From Baseline in 30-minute Postprandial Insulin Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

44.  Secondary:

Change From Baseline in 60-minute Postprandial Insulin Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

45.  Secondary:

Change From Baseline in 15-minute Postprandial Insulin Excursion at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

46.  Secondary:

Change From Baseline in 30-minute Postprandial Insulin Excursion at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

47.  Secondary:

Change From Baseline in 60-minute Postprandial Insulin Excursion at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

48.  Secondary:

Change From Baseline in 15-minute Postprandial C-peptide Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

49.  Secondary:

Change From Baseline in 30-minute Postprandial C-peptide Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

50.  Secondary:

Change From Baseline in 60-minute Postprandial C-peptide Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

51.  Secondary:

Change From Baseline in 15-minute Postprandial C-peptide Excursion at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

52.  Secondary:

Change From Baseline in 30-minute Postprandial C-peptide Excursion at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

53.  Secondary:

Change From Baseline in 60-minute Postprandial C-peptide Excursion at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

54.  Secondary:

Change From Baseline in 30-minute Postprandial Glucagon at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

55.  Secondary:

Change From Baseline in 30-minute Postprandial Glucagon at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

56.  Secondary:

Change From Baseline in 30-minute Postprandial Free Fatty Acids (FFA) at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

57.  Secondary:

Change From Baseline in 30-minute Postprandial FFA at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

58.  Secondary:

Change From Baseline in 30-minute Postprandial Glucagon Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

59.  Secondary:

Change From Baseline in 30-minute Postprandial Glucagon Excursion at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

60.  Secondary:

Change From Baseline in 30-minute Postprandial FFA Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

61.  Secondary:

Change From Baseline in 30-minute Postprandial FFA Excursion at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

62.  Secondary:

Change From Baseline in 15-minute Insulinogenic Index at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

63.  Secondary:

Change From Baseline in 15-minute Insulinogenic Index at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

64.  Secondary:

Change From Baseline in 30-minute Insulinogenic Index at Week 6 in the 0-40 and 0 & 100 mg Cohorts.   [ Time Frame: Baseline, Week 6 ]

65.  Secondary:

Change From Baseline in 30-minute Insulinogenic Index at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

66.  Secondary:

Change From Baseline in Matsuda Index at Week 6 in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 6 ]

67.  Secondary:

Change From Baseline in Matsuda Index at Week 12 in the 0-40 mg Cohort   [ Time Frame: Baseline, Week 12 ]

68.  Secondary:

Change From Baseline in A1C at 2 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 14 ]

69.  Secondary:

Change From Baseline in A1C at 4 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 10, Week 16 ]

70.  Secondary:

Change From Baseline in FSG at 2 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 8, Week 14 ]

71.  Secondary:

Change From Baseline in FSG at 4 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 10, Week 16 ]

72.  Secondary:

Change From Baseline in Fructosamine at 2 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 8, Week 14 ]

73.  Secondary:

Change From Baseline in Fructosamine at 4 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts   [ Time Frame: Baseline, Week 10, Week 16 ]

74.  Secondary:

Change From Baseline in A1C at Week 6 by Baseline A1C Category in the 0 & 100 Cohort   [ Time Frame: Baseline, Week 6 ]

75.  Secondary:

Change From Baseline in FSG at Week 6 in Subjects by Baseline FSG Category in the 0 & 100 mg Cohort.   [ Time Frame: Baseline, Week 6 ]

76.  Secondary:

Change From Baseline in 60 Minute Postprandial Glucose at Week 6 by Baseline Category in the 0 & 100 mg Cohort   [ Time Frame: Baseline, Week 6 ]

77.  Secondary:

Percentage of Participants Achieving A1C < 7% at Week 6 in the 0 & 100 mg Cohort   [ Time Frame: Week 6 ]

78.  Secondary:

Change From Baseline in 60-minute Postprandial FFA Excursion at Week 6 in the 0 & 100 mg Cohort   [ Time Frame: Baseline, Week 6 ]

79.  Secondary:

Change From Baseline in 60-minute Postprandial Glucagon Excursion at Week 6 in the 0 & 100 mg Cohort   [ Time Frame: Baseline, Week 6 ]

80.  Secondary:

Discontinuations During the Double-Blind Phase Due to Lack of Glycemic Control   [ Time Frame: Week 4, Week 6 ]

81.  Secondary:

Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations During the Double-Blind Treatment Period in the 0-40 mg Cohort   [ Time Frame: up to Week 12 for AEs; up to 30 days post-double-blind period but prior to follow-up period if any for SAEs and up to 30 days post-double-blind period for Discontinuations ]

82.  Secondary:

Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations During the Double-Blind Treatment Period in the 0 & 100 mg Cohort   [ Time Frame: up to Week 6 for AEs; up to 30 days post-double-blind period but prior to follow-up period if any for SAEs and up to 30 days post-double-blind period for Discontinuations ]

83.  Secondary:

Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations During the Follow-up Period in the 0-40 mg Cohort   [ Time Frame: From Week 12 to Week 16 for AEs; up to 30 days post follow-up in both cohorts for SAEs and Discontinuations ]

84.  Secondary:

Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations During the Follow-up Period in the 0 & 100 mg Cohort   [ Time Frame: From Week 6 to Week 10 for AEs; up to 30 days post follow-up in both cohorts for SAEs and Discontinuations ]