Long-term Safety Study of Alogliptin in Participants With Type 2 Diabetes in Japan

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Takeda Global Research & Development Center, Inc. ( Takeda Pharmaceutical Company Limited )

ClinicalTrials.gov Identifier:

NCT01263496

First received: December 17, 2010

Last updated: February 1, 2012

Last verified: February 2012

History of Changes

Results First Received: June 8, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Type 2 Diabetes Mellitus
Interventions:	Drug: Alogliptin Drug: Voglibose

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 enrolled at 53 investigative sites in Japan from 10 May 2007 to 27 September 2008.

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 with uncontrolled blood glucose despite diet and exercise therapies were enrolled in one of 5, once-daily (QD) or three-times daily (TID) treatment groups. Analyses were performed by treatment dose group or by treatment dose in this study.

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 with uncontrolled blood glucose despite diet and exercise therapies were enrolled in one of 5, once-daily (QD) or three-times daily (TID) treatment groups.

Analyses were performed by treatment dose group or by treatment dose in this study.

Reporting Groups

	Description
Alogliptin 6.25 mg Dose Group* → Alogliptin 6.25 mg Dose Group	Alogliptin 6.5 mg, tablets, orally, once daily and voglibose 0.2 mg, tablets, orally, three times daily for up to 40 weeks. *for participants from the 6.5 mg dosing ARM of the SYR-322/CCT-001 (NCT01263470) dose-ranging study.
Alogliptin 12.5 mg Dose Group* → Alogliptin 12.5 mg Dose Group	Alogliptin 12.5 mg, tablets, orally, once daily and voglibose 0.2 mg, tablets, orally, three times daily for up to 40 weeks. *for participants from the 12.5 mg dosing ARM of the SYR-322/CCT-001 (NCT01263470) dose-ranging study.
Alogliptin 25 mg Dose Group* → Alogliptin 25 mg Dose Group	Alogliptin 25 mg, tablets, orally, once daily and voglibose 0.2 mg, tablets, orally, three times daily for up to 40 weeks. *for participants from the 25 mg dosing ARM of the SYR-322/CCT-001 (NCT01263470) dose-ranging study.
Alogliptin 50 mg Dose Group* → Alogliptin 50 mg Dose Group	Alogliptin 50 mg, tablets, orally, once daily and voglibose 0.2 mg, tablets, orally, three times daily for up to 40 weeks. *for participants from the 50 mg dosing ARM of the SYR-322/CCT-001 (NCT01263470) dose-ranging study.
Voglibose 0.2 mg Dose Group* → Voglibose 0.2 mg Dose Group	Voglibose 0.2 mg, tablets, orally, three times daily for up to 40 weeks. *for participants from the voglibose 0.2 mg dosing ARM of the SYR-322/CCT-001 (NCT01263470) dose-ranging study.
Placebo Dose Group* → Alogliptin 6.25 mg Dose Group	Placebo-matching tablets, orally, once or three times daily for up to 40 weeks. *for participants from the placebo dosing ARM of the SYR-322/CCT-001 (NCT01263470) dose-ranging study.
Placebo Dose Group* → Alogliptin 12.5 mg Dose Group	Placebo-matching tablets, orally, once or three times daily for up to 40 weeks. *for participants from the placebo dosing ARM of the SYR-322/CCT-001 (NCT01263470) dose-ranging study.
Placebo Dose Group* → Alogliptin 25 mg Dose Group	Placebo-matching tablets, orally, once or three times daily for up to 40 weeks. *for participants from the placebo dosing ARM of the SYR-322/CCT-001 (NCT01263470) dose-ranging study.
Placebo Dose Group* → Alogliptin 50 mg Dose Group	Placebo-matching tablets, orally, once or three times daily for up to 40 weeks. *for participants from the placebo dosing ARM of the SYR-322/CCT-001 (NCT01263470) dose-ranging study.

Participant Flow for 2 periods

Period 1: Enrolled - Long-Term Extension Study

	Alogliptin 6.25 mg Dose Group* → Alogliptin 6.25 mg Dose Group	Alogliptin 12.5 mg Dose Group* → Alogliptin 12.5 mg Dose Group	Alogliptin 25 mg Dose Group* → Alogliptin 25 mg Dose Group	Alogliptin 50 mg Dose Group* → Alogliptin 50 mg Dose Group	Voglibose 0.2 mg Dose Group* → Voglibose 0.2 mg Dose Group	Placebo Dose Group* → Alogliptin 6.25 mg Dose Group	Placebo Dose Group* → Alogliptin 12.5 mg Dose Group	Placebo Dose Group* → Alogliptin 25 mg Dose Group	Placebo Dose Group* → Alogliptin 50 mg Dose Group
STARTED	72	75	72	75	74	17	17	18	18
COMPLETED	71	75	72	74	72	17	17	18	18
NOT COMPLETED	1	0	0	1	2	0	0	0	0
Protocol Violation	1	0	0	0	0	0	0	0	0
Adverse Event	0	0	0	1	2	0	0	0	0

Period 2: Entered - Long-Term Extension Study

	Alogliptin 6.25 mg Dose Group* → Alogliptin 6.25 mg Dose Group	Alogliptin 12.5 mg Dose Group* → Alogliptin 12.5 mg Dose Group	Alogliptin 25 mg Dose Group* → Alogliptin 25 mg Dose Group	Alogliptin 50 mg Dose Group* → Alogliptin 50 mg Dose Group	Voglibose 0.2 mg Dose Group* → Voglibose 0.2 mg Dose Group	Placebo Dose Group* → Alogliptin 6.25 mg Dose Group	Placebo Dose Group* → Alogliptin 12.5 mg Dose Group	Placebo Dose Group* → Alogliptin 25 mg Dose Group	Placebo Dose Group* → Alogliptin 50 mg Dose Group
STARTED	71	72 ^[1]	72	74	71 ^[2]	17	17	17 ^[2]	18
COMPLETED	62	59	62	68	61	16	16	16	15
NOT COMPLETED	9	13	10	6	10	1	1	1	3
Adverse Event	0	5	6	3	1	0	0	0	1
Lost to Follow-up	0	2	0	0	0	0	0	0	0
Withdrawal by Subject	1	2	0	2	4	1	1	0	1
Lack of Efficacy	8	4	4	1	5	0	0	0	1
Participant Unavailability	0	0	0	0	0	0	0	1	0

[1]	3 participants did not enter from previous period (1 voluntary withdraw; 2 did not meet criteria).
[2]	1 participant did not enter from previous period (voluntary withdraw).

Baseline Characteristics

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Reporting Groups

	Description
Alogliptin 6.25 mg QD	Alogliptin 6.25 mg, tablets, orally, once daily for up to 40 weeks.
Alogliptin 12.5 mg QD	Alogliptin 12.5 mg, tablets, orally, once daily for up to 40 weeks.
Alogliptin 25 mg QD	Alogliptin 25 mg, tablets, orally, once daily for up to 40 weeks.
Alogliptin 50 mg QD	Alogliptin 50 mg, tablets, orally, once daily for up to 40 weeks.
Voglibose 0.2 mg TID	Voglibose 0.2 mg, tablets, orally, three times daily for up to 40 weeks.
Total	Total of all reporting groups

Baseline Measures

	Alogliptin 6.25 mg QD	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD	Alogliptin 50 mg QD	Voglibose 0.2 mg TID	Total
Number of Participants [units: participants]	96	101	97	97	83	474
Age, Customized [units: participants]
≤ 64 years	69	67	64	65	51	316
≥ 65 years	27	34	33	32	32	158
Gender [units: participants]
Female	26	29	22	29	27	133
Male	70	72	75	68	56	341

Outcome Measures

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1. Primary:

Number of Participants With Adverse Events. [ Time Frame: 52 Weeks. ]

Show Outcome Measure 1

2. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 12). [ Time Frame: Baseline and Week 12. ]

Show Outcome Measure 2

3. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 16). [ Time Frame: Baseline and Week 16. ]

Show Outcome Measure 3

4. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 20). [ Time Frame: Baseline and Week 20. ]

Show Outcome Measure 4

5. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 24). [ Time Frame: Baseline and Week 24. ]

Show Outcome Measure 5

6. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 28). [ Time Frame: Baseline and Week 28. ]

Show Outcome Measure 6

7. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 32). [ Time Frame: Baseline and Week 32. ]

Show Outcome Measure 7

8. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 36). [ Time Frame: Baseline and Week 36. ]

Show Outcome Measure 8

9. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 40). [ Time Frame: Baseline and Week 40. ]

Show Outcome Measure 9

10. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 44). [ Time Frame: Baseline and Week 44. ]

Show Outcome Measure 10

11. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 48). [ Time Frame: Baseline and Week 48. ]

Show Outcome Measure 11

12. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 52). [ Time Frame: Baseline and Week 52. ]

Show Outcome Measure 12

13. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ]

Show Outcome Measure 13

14. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 12). [ Time Frame: Baseline and Week 12 ]

Show Outcome Measure 14

15. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 16). [ Time Frame: Baseline and Week 16. ]

Show Outcome Measure 15

16. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 20). [ Time Frame: Baseline and Week 20. ]

Show Outcome Measure 16

17. Secondary:

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

Show Outcome Measure 17

18. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 28). [ Time Frame: Baseline and Week 28. ]

Show Outcome Measure 18

19. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 32). [ Time Frame: Baseline and Week 32. ]

Show Outcome Measure 19

20. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 36). [ Time Frame: Baseline and Week 36. ]

Show Outcome Measure 20

21. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 40). [ Time Frame: Baseline and Week 40. ]

Show Outcome Measure 21

22. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 44). [ Time Frame: Baseline and Week 44. ]

Show Outcome Measure 22

23. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 48). [ Time Frame: Baseline and Week 48. ]

Show Outcome Measure 23

24. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 52). [ Time Frame: Baseline and Week 52. ]

Show Outcome Measure 24

25. Secondary:

Change From Baseline in Fasting Plasma Glucose (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ]

Show Outcome Measure 25

26. Secondary:

Change From Baseline in Fasting C-peptide (Week 12). [ Time Frame: Baseline and Week 12. ]

Show Outcome Measure 26

27. Secondary:

Change From Baseline in Fasting C-peptide (Week 16). [ Time Frame: Baseline and Week 16. ]

Show Outcome Measure 27

28. Secondary:

Change From Baseline in Fasting C-peptide (Week 20). [ Time Frame: Baseline and Week 20. ]

Show Outcome Measure 28

29. Secondary:

Change From Baseline in Fasting C-peptide (Week 24). [ Time Frame: Baseline and Week 24. ]

Show Outcome Measure 29

30. Secondary:

Change From Baseline in Fasting C-peptide (Week 28). [ Time Frame: Baseline and Week 28. ]

Show Outcome Measure 30

31. Secondary:

Change From Baseline in Fasting C-peptide (Week 32). [ Time Frame: Baseline and Week 32. ]

Show Outcome Measure 31

32. Secondary:

Change From Baseline in Fasting C-peptide (Week 36). [ Time Frame: Baseline and Week 36. ]

Show Outcome Measure 32

33. Secondary:

Change From Baseline in Fasting C-peptide (Week 40). [ Time Frame: Baseline and Week 40. ]

Show Outcome Measure 33

34. Secondary:

Change From Baseline in Fasting C-peptide (Week 44). [ Time Frame: Baseline and Week 44. ]

Show Outcome Measure 34

35. Secondary:

Change From Baseline in Fasting C-peptide (Week 48). [ Time Frame: Baseline and Week 48. ]

Show Outcome Measure 35

36. Secondary:

Change From Baseline in Fasting C-peptide (Week 52). [ Time Frame: Baseline and Week 52. ]

Show Outcome Measure 36

37. Secondary:

Change From Baseline in Fasting C-peptide (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ]

Show Outcome Measure 37

38. Secondary:

Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value) (Week 12). [ Time Frame: Baseline and Week 12. ]

Show Outcome Measure 38

39. Secondary:

Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value) (Week 24). [ Time Frame: Baseline and Week 24. ]

Show Outcome Measure 39

40. Secondary:

Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value) (Week 52). [ Time Frame: Baseline and Week 52. ]

Show Outcome Measure 40

41. Secondary:

Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value) (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ]

Show Outcome Measure 41

42. Secondary:

Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)) (Week 12). [ Time Frame: Baseline and Week 12. ]

Show Outcome Measure 42

43. Secondary:

Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)) (Week 24). [ Time Frame: Baseline and Week 24. ]

Show Outcome Measure 43

44. Secondary:

Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)) (Week 52). [ Time Frame: Baseline and Week 52. ]

Show Outcome Measure 44

45. Secondary:

Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)) (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ]

Show Outcome Measure 45

46. Secondary:

Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2)) (Week 12). [ Time Frame: Baseline and Week 12. ]

Show Outcome Measure 46

47. Secondary:

Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2)) (Week 24). [ Time Frame: Baseline and Week 24. ]

Show Outcome Measure 47

48. Secondary:

Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2)) (Week 52). [ Time Frame: Baseline and Week 52. ]

Show Outcome Measure 48

49. Secondary:

Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2)) (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ]

Show Outcome Measure 49

50. Secondary:

Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 12). [ Time Frame: Baseline and Week 12 ]

Show Outcome Measure 50

51. Secondary:

Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 24). [ Time Frame: Baseline and Week 24. ]

Hide Outcome Measure 51

Measure Type	Secondary
Measure Title	Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 24).
Measure Description	The change between the value of insulin collected at week 24 and insulin collected at baseline as measured by the meal tolerance test. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and 2 hours after the start of the meal.
Time Frame	Baseline and 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.
Values are Summary Statistics.

Reporting Groups

	Description
Alogliptin 6.25 mg QD	Alogliptin 6.25 mg, tablets, orally, once daily for up to 40 weeks.
Alogliptin 12.5 mg QD	Alogliptin 12.5 mg, tablets, orally, once daily for up to 40 weeks.
Alogliptin 25 mg QD	Alogliptin 25 mg, tablets, orally, once daily for up to 40 weeks.
Alogliptin 50 mg QD	Alogliptin 50 mg, tablets, orally, once daily for up to 40 weeks.
Voglibose 0.2 mg TID	Voglibose 0.2 mg, tablets, orally, three times daily for up to 40 weeks.

Measured Values

	Alogliptin 6.25 mg QD	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD	Alogliptin 50 mg QD	Voglibose 0.2 mg TID
Number of Participants Analyzed [units: participants]	61	64	68	71	59
Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 24). [units: μU·hr/mL] Mean ± Standard Deviation	-1.89 ± 21.943	4.50 ± 12.876	2.85 ± 12.309	-0.98 ± 27.457	-16.21 ± 20.927

Statistical Analysis 1 for Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 24).

Groups ^[1]	Alogliptin 6.25 mg QD vs. Voglibose 0.2 mg TID
Mean Difference (Final Values) ^[2]	14.323
95% Confidence Interval	( 6.567 to 22.079 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
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Statistical Analysis 2 for Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 24).

Groups ^[1]	Alogliptin 12.5 mg QD vs. Voglibose 0.2 mg TID
Mean Difference (Final Values) ^[2]	20.714
95% Confidence Interval	( 14.563 to 26.864 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 24).

Groups ^[1]	Alogliptin 25 mg QD vs. Voglibose 0.2 mg TID
Mean Difference (Final Values) ^[2]	19.063
95% Confidence Interval	( 13.125 to 25.002 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
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Statistical Analysis 4 for Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 24).

Groups ^[1]	Alogliptin 50 mg QD vs. Voglibose 0.2 mg TID
Mean Difference (Final Values) ^[2]	15.233
95% Confidence Interval	( 6.618 to 23.847 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
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52. Secondary:

Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 52). [ Time Frame: Baseline and Week 52. ]

Show Outcome Measure 52

53. Secondary:

Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ]

Show Outcome Measure 53

54. Secondary:

Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)) (Week 12). [ Time Frame: Baseline and Week 12 ]

Show Outcome Measure 54

55. Secondary:

Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)) (Week 24). [ Time Frame: Baseline and Week 24. ]

Show Outcome Measure 55

56. Secondary:

Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)) (Week 52). [ Time Frame: Baseline and Week 52. ]

Show Outcome Measure 56

57. Secondary:

Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)) (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ]

Show Outcome Measure 57

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: The clinical trial contract states that information should never be disclosed without prior consent of the sponsor, although it does not specify the number of days during which disclosure of information is limited.

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: General Manager
Organization: Japan Development Center, Pharmaceutical Development Division
phone: +81-6-6204-5257
e-mail: clinicaltrialregistry@tpna.com

No publications provided

Responsible Party:	Takeda Global Research & Development Center, Inc. ( Takeda Pharmaceutical Company Limited )
ClinicalTrials.gov Identifier:	NCT01263496 History of Changes
Other Study ID Numbers:	SYR-322/OCT-001, U1111-1118-4027
Study First Received:	December 17, 2010
Results First Received:	June 8, 2011
Last Updated:	February 1, 2012
Health Authority:	Japan: Ministry of Health, Labor and Welfare

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