Study of Alogliptin Combined With Sulfonylurea in Subjects With Type 2 Diabetes Mellitus.

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Takeda Global Research & Development Center, Inc.

ClinicalTrials.gov Identifier:

NCT00286468

First received: February 1, 2006

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: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Diabetes Mellitus
Interventions:	Drug: Alogliptin and glyburide Drug: Glyburide

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 125 investigative sites in Argentina, Australia, Brazil, Chile, Dominican Republic, Germany, Guatemala, India, Mexico, New Zealand, The Netherlands, Poland, South Africa, Spain, and the United States from 04 April 2006 to 20 June 2007.

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 who were inadequately controlled while receiving a stable dose of glyburide monotherapy were enrolled in one of 3, once-daily (QD) treatment groups.

Reporting Groups

	Description
Placebo	Alogliptin placebo-matching tablets, orally, once daily and glyburide for up to 26 weeks.
Alogliptin 12.5 mg QD	Alogliptin 12.5 mg, tablets, orally, once daily and glyburide for up to 26 weeks.
Alogliptin 25 mg QD	Alogliptin 25 mg, tablets, orally, once daily and glyburide for up to 26 weeks.

Participant Flow: Overall Study

	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
STARTED	99	203	198
COMPLETED	62	153	148
NOT COMPLETED	37	50	50
Hyperglycemic Rescue	28	30	31
Adverse Event	2	6	4
Protocol Violation	0	3	1
Lost to Follow-up	1	1	2
Withdrawal by Subject	3	8	11
Physician Decision	3	2	1

Baseline Characteristics

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Reporting Groups

	Description
Placebo	Alogliptin placebo-matching tablets, orally, once daily and glyburide for up to 26 weeks.
Alogliptin 12.5 mg QD	Alogliptin 12.5 mg, tablets, orally, once daily and glyburide for up to 26 weeks.
Alogliptin 25 mg QD	Alogliptin 25 mg, tablets, orally, once daily and glyburide for up to 26 weeks.
Total	Total of all reporting groups

Baseline Measures

	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD	Total
Number of Participants [units: participants]	99	203	198	500
Age, Customized [units: participants]
<65 years	72	153	145	370
Between 65 and 74 years	23	42	47	112
≥75 years	4	8	6	18
Gender [units: participants]
Female	48	92	99	239
Male	51	111	99	261

Outcome Measures

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1. Primary:

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26. [ Time Frame: Baseline and Week 26. ]

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2. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 4). [ Time Frame: Baseline and Week 4. ]

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3. Secondary:

Change From Baseline in Glycosylated Hemoglobin (Week 8). [ Time Frame: Baseline and Week 8. ]

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4. Secondary:

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

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5. Secondary:

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

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6. Secondary:

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

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7. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 1). [ Time Frame: Baseline and Week 1. ]

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8. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 2). [ Time Frame: Baseline and Week 2. ]

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9. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 4). [ Time Frame: Baseline and Week 4. ]

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10. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 8). [ Time Frame: Baseline and Week 8. ]

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11. Secondary:

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

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12. Secondary:

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

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13. Secondary:

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

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14. Secondary:

Change From Baseline in Fasting Plasma Glucose (Week 26). [ Time Frame: Baseline and Week 26. ]

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15. Secondary:

Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL). [ Time Frame: 26 Weeks. ]

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16. Secondary:

Number of Participants Requiring Rescue. [ Time Frame: 26 Weeks. ]

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17. Secondary:

Change From Baseline in Fasting Proinsulin (Week 4). [ Time Frame: Baseline and Week 4. ]

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18. Secondary:

Change From Baseline in Fasting Proinsulin (Week 8). [ Time Frame: Baseline and Week 8. ]

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19. Secondary:

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

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20. Secondary:

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

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21. Secondary:

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

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22. Secondary:

Change From Baseline in Fasting Proinsulin (Week 26). [ Time Frame: Baseline and Week 26. ]

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23. Secondary:

Change From Baseline in Insulin (Week 4). [ Time Frame: Baseline and Week 4. ]

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24. Secondary:

Change From Baseline in Insulin (Week 8). [ Time Frame: Baseline and Week 8. ]

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25. Secondary:

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

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26. Secondary:

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

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27. Secondary:

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

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28. Secondary:

Change From Baseline in Insulin (Week 26). [ Time Frame: Baseline and Week 26. ]

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29. Secondary:

Change From Baseline in Proinsulin/Insulin Ratio (Week 4). [ Time Frame: Baseline and Week 4. ]

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30. Secondary:

Change From Baseline in Proinsulin/Insulin Ratio (Week 8). [ Time Frame: Baseline and Week 8. ]

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31. Secondary:

Change From Baseline in Proinsulin/Insulin Ratio (Week 12). [ Time Frame: Baseline and Week 12. ]

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32. Secondary:

Change From Baseline in Proinsulin/Insulin Ratio (Week 16). [ Time Frame: Baseline and Week 16. ]

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33. Secondary:

Change From Baseline in Proinsulin/Insulin Ratio (Week 20). [ Time Frame: Baseline and Week 20. ]

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34. Secondary:

Change From Baseline in Proinsulin/Insulin Ratio (Week 26). [ Time Frame: Baseline and Week 26. ]

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35. Secondary:

Change From Baseline in C-peptide (Week 4). [ Time Frame: Baseline and Week 4. ]

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36. Secondary:

Change From Baseline in C-peptide (Week 8). [ Time Frame: Baseline and Week 8. ]

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37. Secondary:

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

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38. Secondary:

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

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39. Secondary:

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

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40. Secondary:

Change From Baseline in C-peptide (Week 26). [ Time Frame: Baseline and Week 26. ]

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41. Secondary:

Number of Participants With Glycosylated Hemoglobin ≤ 6.5%. [ Time Frame: Baseline and Week 26. ]

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42. Secondary:

Number of Participants With Glycosylated Hemoglobin ≤ 7.0%. [ Time Frame: Baseline and Week 26. ]

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43. Secondary:

Number of Participants With Glycosylated Hemoglobin ≤ 7.5%. [ Time Frame: Baseline and Week 26. ]

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44. Secondary:

Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%. [ Time Frame: Baseline and Week 26. ]

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45. Secondary:

Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%. [ Time Frame: Baseline and Week 26. ]

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46. Secondary:

Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%. [ Time Frame: Baseline and Week 26. ]

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47. Secondary:

Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%. [ Time Frame: Baseline and Week 26. ]

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48. Secondary:

Change From Baseline in Body Weight (Week 8). [ Time Frame: Baseline and Week 8. ]

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49. Secondary:

Change From Baseline in Body Weight (Week 12). [ Time Frame: Baseline and Week 12. ]

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50. Secondary:

Change From Baseline in Body Weight (Week 20). [ Time Frame: Baseline and Week 20. ]

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51. Secondary:

Change From Baseline in Body Weight (Week 26). [ Time Frame: Baseline and Week 26. ]

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Measure Type	Secondary
Measure Title	Change From Baseline in Body Weight (Week 26).
Measure Description	The change between Body Weight measured at week 26 or final visit and Body Weight measured at baseline.
Time Frame	Baseline and Week 26.
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 who received at least one dose of study drug (Full Analysis Set), and who had measurements at baseline and at the visit. Missing data are imputed using last observation carried forward (LOCF).

Reporting Groups

	Description
Placebo	Alogliptin placebo-matching tablets, orally, once daily and glyburide for up to 26 weeks.
Alogliptin 12.5 mg QD	Alogliptin 12.5 mg, tablets, orally, once daily and glyburide for up to 26 weeks.
Alogliptin 25 mg QD	Alogliptin 25 mg, tablets, orally, once daily and glyburide for up to 26 weeks.

Measured Values

	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Number of Participants Analyzed [units: participants]	96	197	195
Change From Baseline in Body Weight (Week 26). [units: kg] Least Squares Mean ± Standard Error	-0.20 ± 0.277	0.60 ± 0.193	0.68 ± 0.194

Statistical Analysis 1 for Change From Baseline in Body Weight (Week 26).

Groups ^[1]	Placebo vs. Alogliptin 12.5 mg QD
Method ^[2]	ANCOVA
P Value ^[3]	0.018
Mean Difference (Final Values) ^[4]	0.80
95% Confidence Interval	( 0.14 to 1.46 )

[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:
	Treatment and geographic region as class variables; baseline glyburide dose and baseline value for the endpoint parameter as covariates.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No multiplicity adjustments.
[4]	Other relevant estimation information:
	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

Statistical Analysis 2 for Change From Baseline in Body Weight (Week 26).

Groups ^[1]	Placebo vs. Alogliptin 25 mg QD
Method ^[2]	ANCOVA
P Value ^[3]	0.010
Mean Difference (Final Values) ^[4]	0.88
95% Confidence Interval	( 0.21 to 1.54 )

[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:
	Treatment and geographic region as class variables; baseline glyburide dose and baseline value for the endpoint parameter as covariates.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No multiplicity adjustments.
[4]	Other relevant estimation information:
	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

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: No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.

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: Sr. VP, Clinical Science
Organization: Takeda Global Research and Development Center, Inc.
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com

Publications of Results:

Pratley RE, Kipnes MS, Fleck PR, Wilson C, Mekki Q; Alogliptin Study 007 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy. Diabetes Obes Metab. 2009 Feb;11(2):167-76.

Pratley RE, McCall T, Fleck PR, Wilson CA, Mekki Q. Alogliptin use in elderly people: a pooled analysis from phase 2 and 3 studies. J Am Geriatr Soc. 2009 Nov;57(11):2011-9. Epub 2009 Sep 30.

Responsible Party:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00286468 History of Changes
Other Study ID Numbers:	SYR-322-SULF-007, 2005-004667-36, U1111-1113-8506
Study First Received:	February 1, 2006
Results First Received:	June 8, 2011
Last Updated:	February 1, 2012
Health Authority:	United States: Food and Drug Administration

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