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

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01318122
• Collaborator: (none)
• Enrollment: 336
• Arms: 2
• Duration (Months): 15

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the long-term safety and efficacy of alogliptin and Thiazolidine administered once daily (QD) for 40 consecutive weeks in participants who completed a phase 2/3 Thiazolidine add on study.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Alogliptin and pioglitazone; Drug: Alogliptin and pioglitazone	Phase 2/Phase 3

Detailed Description

Both insulin hyposecretion and insulin-resistance are considered to be involved in the development of type 2 diabetes mellitus.

Takeda is developing SYR-322 (alogliptin) for the improvement of glycemic control in patients with type 2 diabetes mellitus. Alogliptin is an inhibitor of the dipeptidyl peptidase IV (DPP-IV) enzyme. DPP-IV is thought to be primarily responsible for the degradation of 2 peptide hormones released in response to nutrient ingestion. It is expected that inhibition of DPP-IV will improve glycemic control in patients with type 2 diabetes.

To evaluate the long-term safety and efficacy of alogliptin, participants in the present study were enrolled from a core phase 2/3 thiazolidine add on study (SYR-322/CCT-004; NCT01318070).

Study Design

• Study Type: Interventional
• Actual Enrollment: 336 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Long-Term, Open-Label Extension Study to Investigate the Long-Term Safety of SYR-322 When Used in Combination With Thiazolidine in Subjects With Type 2 Diabetes in Japan
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Drug: Alogliptin and pioglitazone; Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.; Other Names: SYR-322 Actos
Active Comparator: Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD	Drug: Alogliptin and pioglitazone; Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.; Other Names: SYR-322 Actos

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events. [52 Weeks.]

   Treatment-emergent adverse events (TEAE) are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pre-treatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing.

Secondary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin (Week 8). [Baseline and Week 8.]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 8 and glycosylated hemoglobin collected at baseline.

2. Change From Baseline in Glycosylated Hemoglobin (Week 12). [Baseline and Week 12.]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 and glycosylated hemoglobin collected at baseline.

3. Change From Baseline in Glycosylated Hemoglobin (Week 16). [Baseline and Week 16.]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 16 and glycosylated hemoglobin collected at baseline.

4. Change From Baseline in Glycosylated Hemoglobin (Week 20). [Baseline and Week 20.]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 20 and glycosylated hemoglobin collected at baseline.

5. Change From Baseline in Glycosylated Hemoglobin (Week 24). [Baseline and Week 24.]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 24 and glycosylated hemoglobin collected at baseline.

6. Change From Baseline in Glycosylated Hemoglobin (Week 28). [Baseline and Week 28.]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 28 and glycosylated hemoglobin collected at baseline.

7. Change From Baseline in Glycosylated Hemoglobin (Week 32). [Baseline and Week 32.]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 32 and glycosylated hemoglobin collected at baseline.

8. Change From Baseline in Glycosylated Hemoglobin (Week 36). [Baseline and Week 36.]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 36 and glycosylated hemoglobin collected at baseline.

9. Change From Baseline in Glycosylated Hemoglobin (Week 40). [Baseline and Week 40.]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 40 and glycosylated hemoglobin collected at baseline.

10. Change From Baseline in Glycosylated Hemoglobin (Week 44). [Baseline and Week 44.]

    The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 44 and glycosylated hemoglobin collected at baseline.

11. Change From Baseline in Glycosylated Hemoglobin (Week 48). [Baseline and Week 48.]

    The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 48 and glycosylated hemoglobin collected at baseline.

12. Change From Baseline in Glycosylated Hemoglobin (Week 52). [Baseline and Week 52.]

    The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 52 and glycosylated hemoglobin collected at baseline.

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

    The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 52 or final visit and glycosylated hemoglobin collected at baseline.

14. Change From Baseline in Fasting Blood Glucose (Week 8). [Baseline and Week 8.]

    The change between the value of fasting blood glucose collected at week 8 and baseline.

15. Change From Baseline in Fasting Blood Glucose (Week 12). [Baseline and Week 12.]

    The change between the value of fasting blood glucose collected at week 12 and baseline.

16. Change From Baseline in Fasting Blood Glucose (Week 16). [Baseline and Week 16.]

    The change between the value of fasting blood glucose collected at week 6 and baseline.

17. Change From Baseline in Fasting Blood Glucose (Week 20). [Baseline and Week 20.]

    The change between the value of fasting blood glucose collected at week 20 and baseline.

18. Change From Baseline in Fasting Blood Glucose (Week 24). [Baseline and Week 24.]

    The change between the value of fasting blood glucose collected at week 24 and baseline.

19. Change From Baseline in Fasting Blood Glucose (Week 28). [Baseline and Week 28.]

    The change between the value of fasting blood glucose collected at week 28 and baseline.

20. Change From Baseline in Fasting Blood Glucose (Week 32). [Baseline and Week 32.]

    The change between the value of fasting blood glucose collected at week 32 and baseline.

21. Change From Baseline in Fasting Blood Glucose (Week 36). [Baseline and Week 36.]

    The change between the value of fasting blood glucose collected at week 36 and baseline.

22. Change From Baseline in Fasting Blood Glucose (Week 40). [Baseline and Week 40.]

    The change between the value of fasting blood glucose collected at week 40 and baseline.

23. Change From Baseline in Fasting Blood Glucose (Week 44). [Baseline and Week 44.]

    The change between the value of fasting blood glucose collected at week 44 and baseline.

24. Change From Baseline in Fasting Blood Glucose (Week 48). [Baseline and Week 48.]

    The change between the value of fasting blood glucose collected at week 48 and baseline.

25. Change From Baseline in Fasting Blood Glucose (Week 52). [Baseline and Week 52.]

    The change between the value of fasting blood glucose collected at week 52 and baseline.

26. Change From Baseline in Fasting Blood Glucose (Final Visit). [Baseline and Final Visit (up to Week 52).]

    The change between the value of fasting blood glucose collected at week 52 or final visit and baseline.

27. Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 12). [Baseline and Week 12.]

    The change between the value of blood glucose measured by the meal tolerance test collected at week 12 and blood glucose measured by the meal tolerance test collected at baseline. Meal tolerance test measures blood glucose through blood samples drawn before a meal and at 2 hours after the start of the meal.

28. Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 24). [Baseline and Week 24.]

    The change between the value of blood glucose measured by the meal tolerance test collected at week 24 and blood glucose measured by the meal tolerance test collected at baseline. Meal tolerance test measures blood glucose through blood samples drawn before a meal and at 2 hours after the start of the meal.

29. Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 52). [Baseline and Week 52.]

    The change between the value of blood glucose measured by the meal tolerance test collected at week 52 or final visit and blood glucose measured by the meal tolerance test collected at baseline. Meal tolerance test measures blood glucose through blood samples drawn before a meal and at 2 hours after the start of the meal.

30. Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Final Visit). [Baseline and Final Visit (up to Week 52).]

    The change between the value of blood glucose measured by the meal tolerance test collected at week 52 or end of study and blood glucose measured by the meal tolerance test collected at baseline. Meal tolerance test measures blood glucose through blood samples drawn before a meal and at 2 hours after the start of the meal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 33 Years to 88 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Had completed the core phase 2/3 thiazolidine add on study.

2. The subject was capable of understanding and complying with protocol requirements.

3. Signed a written, informed consent form prior to the initiation of any study procedure.

Exclusion Criteria:

1. With clinical manifestation of hepatic impairment (e.g., an AST or ALT value of 2.5 times or more of the upper reference limit at Week 8 of the core phase 2/3 thiazolidine add on study).

2. With clinical manifestation of renal impairment (e.g., a creatinine value of 2 mg/dL or more at Week 8 of the core phase 2/3 thiazolidine add on study).

3. With a history or symptoms of cardiac failure.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Professor, Department of Medicine, Department of Medicine, Kawasaki Medical School

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT01318122
• Other Study ID Numbers: SYR-322/OCT-004; U1111-1119-6207
• First Posted: Mar 18, 2011
• Last Update Posted: Feb 3, 2012
• Last Verified: Feb 1, 2012

• Keywords provided by Takeda: Diabetes Mellitus - Type 2; Diabetes Mellitus; Drug Therapy
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Pioglitazone; Alogliptin

Study Results

Participant Flow

Recruitment Details	Participants enrolled at 32 investigative sites in Japan from 10 May 2008 to 03 August 2009.
Pre-assignment Detail	Participants who had completed the core phase 2/3 thiazolidine add on study (SYR-322/CCT-004; NCT01318070) were enrolled in one of 2, once-daily (QD) treatment groups.

Arm/Group Title	CCT/004 - 12.5 mg Dose Group* → 12.5 mg Combination Group	CCT/004 - 25 mg Dose Group* → 25 mg Combination Dose Group	Pioglitazone Monotherapy Group* → 12.5 mg Combination Group	Pioglitazone Monotherapy Group* → 25 mg Combination Group
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks. *for participants from the 12.5 mg combination dosing ARM of the SYR-322/CCT-004 (NCT01318070) core phase 2/3 pioglitazone add-on study.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks. *for participants from the 25 mg combination dosing ARM of the SYR-322/CCT-004 (NCT01318070) core phase 2/3 pioglitazone add-on study.	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks. *for participants from the pioglitazone 15 mg or 30 mg dosing ARM of the SYR-322/CCT-004 (NCT01318070) core phase 2/3 pioglitazone add-on study.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks. *for participants from the pioglitazone 15 mg or 30 mg dosing ARM of the SYR-322/CCT-004 (NCT01318070) core phase 2/3 pioglitazone add-on study.
Period Title: Enrolled - Long-Term Extension Study
STARTED	106	110	57	53
COMPLETED	105	110	55	52
NOT COMPLETED	1	0	2	1
Period Title: Enrolled - Long-Term Extension Study
STARTED	105	110	55	52
COMPLETED	96	99	49	48
NOT COMPLETED	9	11	6	4

Baseline Characteristics

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD	Total
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Total of all reporting groups
Overall Participants	166	165	331
Age, Customized (participants) [Number]
≤ 64 years	116 69.9%	103 62.4%	219 66.2%
≥ 65 years	50 30.1%	62 37.6%	112 33.8%
Sex: Female, Male (Count of Participants)
Female	65 39.2%	58 35.2%	123 37.2%
Male	101 60.8%	107 64.8%	208 62.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events.
Description	Treatment-emergent adverse events (TEAE) are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pre-treatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing.
Time Frame	52 Weeks.

Outcome Measure Data

Analysis Population Description

Full Analysis Set was defined as the population of participants randomized in the core phase 2/3 thiazolidine add on study (SYR-322/CCT-004 study; NCT01318070) and received at least 1 dose of the investigational products (SYR-322DB in combination with pioglitazone) for the treatment period.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	166	165
Number of Participants with Serious Adverse Event	14 8.4%	11 6.7%
Number of Participants with Other Adverse Event	143 86.1%	146 88.5%

2. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 8).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 8 and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 8.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	165	164
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.68 (0.371)	-0.73 (0.415)

3. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 12).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 12.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	161	163
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.81 (0.459)	-0.88 (0.519)

4. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 16).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 16 and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 16.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	158	160
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.86 (0.550)	-0.92 (0.571)

5. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 20).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 20 and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 20.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	155	160
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.84 (0.616)	-0.90 (0.581)

6. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 24).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 24 and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	155	158
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.78 (0.612)	-0.82 (0.585)

7. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 28).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 28 and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 28.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	151	156
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.75 (0.620)	-0.76 (0.597)

8. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 32).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 32 and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 32.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	150	152
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.72 (0.605)	-0.72 (0.632)

9. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 36).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 36 and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 36.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	147	151
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.67 (0.575)	-0.69 (0.599)

10. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 40).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 40 and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 40.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	147	150
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.65 (0.573)	-0.66 (0.603)

11. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 44).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 44 and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 44.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	98	101
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.70 (0.577)	-0.74 (0.629)

12. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 48).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 48 and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 48.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	98	101
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.73 (0.596)	-0.76 (0.683)

13. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 52).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 52 and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 52.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	96	100
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.77 (0.571)	-0.79 (0.633)

14. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Final Visit).
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 52 or final visit and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Final Visit (up to Week 52).

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	166	165
Mean (Standard Deviation) [percentage of Glycosylated Hemoglobin]	-0.65 (0.597)	-0.65 (0.659)

15. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Week 8).
Description	The change between the value of fasting blood glucose collected at week 8 and baseline.
Time Frame	Baseline and Week 8.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	165	164
Mean (Standard Deviation) [mg/dL]	-15.5 (19.60)	-18.1 (20.82)

16. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Week 12).
Description	The change between the value of fasting blood glucose collected at week 12 and baseline.
Time Frame	Baseline and Week 12.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	161	163
Mean (Standard Deviation) [mg/dL]	-13.4 (18.37)	-16.3 (20.54)

17. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Week 16).
Description	The change between the value of fasting blood glucose collected at week 6 and baseline.
Time Frame	Baseline and Week 16.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	158	160
Mean (Standard Deviation) [mg/dL]	-11.9 (22.04)	-13.4 (20.81)

18. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Week 20).
Description	The change between the value of fasting blood glucose collected at week 20 and baseline.
Time Frame	Baseline and Week 20.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	155	160
Mean (Standard Deviation) [mg/dL]	-10.1 (21.07)	-13.9 (21.74)

19. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Week 24).
Description	The change between the value of fasting blood glucose collected at week 24 and baseline.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	155	158
Mean (Standard Deviation) [mg/dL]	-10.0 (21.50)	-10.7 (23.02)

20. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Week 28).
Description	The change between the value of fasting blood glucose collected at week 28 and baseline.
Time Frame	Baseline and Week 28.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	151	156
Mean (Standard Deviation) [mg/dL]	-5.6 (28.42)	-9.1 (21.27)

21. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Week 32).
Description	The change between the value of fasting blood glucose collected at week 32 and baseline.
Time Frame	Baseline and Week 32.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	150	152
Mean (Standard Deviation) [mg/dL]	-7.9 (20.25)	-10.4 (21.27)

22. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Week 36).
Description	The change between the value of fasting blood glucose collected at week 36 and baseline.
Time Frame	Baseline and Week 36.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	147	151
Mean (Standard Deviation) [mg/dL]	-7.1 (19.65)	-11.9 (18.33)

23. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Week 40).
Description	The change between the value of fasting blood glucose collected at week 40 and baseline.
Time Frame	Baseline and Week 40.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	147	150
Mean (Standard Deviation) [mg/dL]	-9.5 (20.76)	-10.6 (27.38)

24. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Week 44).
Description	The change between the value of fasting blood glucose collected at week 44 and baseline.
Time Frame	Baseline and Week 44.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	98	101
Mean (Standard Deviation) [mg/dL]	-10.4 (17.43)	-10.4 (21.24)

25. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Week 48).
Description	The change between the value of fasting blood glucose collected at week 48 and baseline.
Time Frame	Baseline and Week 48.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	98	101
Mean (Standard Deviation) [mg/dL]	-12.2 (19.89)	-14.0 (21.91)

26. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Week 52).
Description	The change between the value of fasting blood glucose collected at week 52 and baseline.
Time Frame	Baseline and Week 52.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	96	100
Mean (Standard Deviation) [mg/dL]	-12.8 (16.63)	-13.6 (26.28)

27. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (Final Visit).
Description	The change between the value of fasting blood glucose collected at week 52 or final visit and baseline.
Time Frame	Baseline and Final Visit (up to Week 52).

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	166	165
Mean (Standard Deviation) [mg/dL]	-11.4 (19.29)	-11.1 (25.19)

28. Secondary Outcome

Title	Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 12).
Description	The change between the value of blood glucose measured by the meal tolerance test collected at week 12 and blood glucose measured by the meal tolerance test collected at baseline. Meal tolerance test measures blood glucose through blood samples drawn before a meal and at 2 hours after the start of the meal.
Time Frame	Baseline and Week 12.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	163	163
Mean (Standard Deviation) [mg/dL]	58.3 (30.81)	49.5 (30.04)

29. Secondary Outcome

Title	Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 24).
Description	The change between the value of blood glucose measured by the meal tolerance test collected at week 24 and blood glucose measured by the meal tolerance test collected at baseline. Meal tolerance test measures blood glucose through blood samples drawn before a meal and at 2 hours after the start of the meal.
Time Frame	Baseline and Week 24.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	104	109
Mean (Standard Deviation) [mg/dL]	55.9 (30.87)	47.9 (29.20)

30. Secondary Outcome

Title	Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 52).
Description	The change between the value of blood glucose measured by the meal tolerance test collected at week 52 or final visit and blood glucose measured by the meal tolerance test collected at baseline. Meal tolerance test measures blood glucose through blood samples drawn before a meal and at 2 hours after the start of the meal.
Time Frame	Baseline and Week 52.

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	146	147
Mean (Standard Deviation) [mg/dL]	59.1 (34.19)	57.2 (31.82)

31. Secondary Outcome

Title	Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Final Visit).
Description	The change between the value of blood glucose measured by the meal tolerance test collected at week 52 or end of study and blood glucose measured by the meal tolerance test collected at baseline. Meal tolerance test measures blood glucose through blood samples drawn before a meal and at 2 hours after the start of the meal.
Time Frame	Baseline and Final Visit (up to Week 52).

Outcome Measure Data

Analysis Population Description

Values are from the Full Analysis Set.

Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD	Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.	Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.
Measure Participants	163	163
Mean (Standard Deviation) [mg/dL]	59.8 (34.26)	56.8 (32.12)

Adverse Events

Time Frame	Treatment-emergent adverse events are any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through receiving the last dose of study drug.
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. 5 participants from alogliptin 12.5 & 25 mg group CCT-004 study did not enter this study.
Arm/Group Title	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD		Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
Arm/Group Description	Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.		Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks. *for participants from the 25 mg combination dosing ARM of the SYR-322/CCT-004 (NCT01318070) core phase 2/3 pioglitazone add-on study.
All Cause Mortality
	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD		Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD		Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/166 (8.4%)		11/165 (6.7%)
Cardiac disorders
Myocardial infarction	1/166 (0.6%)		1/165 (0.6%)
Cardiac failure congestive	0/166 (0%)		1/165 (0.6%)
Ear and labyrinth disorders
Vertigo	1/166 (0.6%)		0/165 (0%)
Eye disorders
Cataract	1/166 (0.6%)		3/165 (1.8%)
Diabetic retinopathy	1/166 (0.6%)		0/165 (0%)
Gastrointestinal disorders
Colonic polyp	1/166 (0.6%)		0/165 (0%)
Duodenal ulcer	0/166 (0%)		1/165 (0.6%)
Enterocele	0/166 (0%)		1/165 (0.6%)
Haemorrhoids	1/166 (0.6%)		0/165 (0%)
Infections and infestations
Epiglottitis	1/166 (0.6%)		0/165 (0%)
Nasopharyngitis	0/166 (0%)		1/165 (0.6%)
Pneumonia	1/166 (0.6%)		0/165 (0%)
Sinusitis	1/166 (0.6%)		0/165 (0%)
Injury, poisoning and procedural complications
Fall	1/166 (0.6%)		2/165 (1.2%)
Alcohol poisoning	0/166 (0%)		1/165 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/166 (0%)		1/165 (0.6%)
Breast cancer	1/166 (0.6%)		0/165 (0%)
Cervix carcinoma	1/166 (0.6%)		0/165 (0%)
Colon cancer	1/166 (0.6%)		0/165 (0%)
Gastric cancer	1/166 (0.6%)		0/165 (0%)
Reproductive system and breast disorders
Prostatitis	1/166 (0.6%)		0/165 (0%)
Other (Not Including Serious) Adverse Events
	Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD		Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	143/166 (86.1%)		146/165 (88.5%)
Eye disorders
Diabetic retinopathy	7/166 (4.2%)		6/165 (3.6%)
Conjunctivitis allergic	1/166 (0.6%)		5/165 (3%)
Gastrointestinal disorders
Constipation	4/166 (2.4%)		11/165 (6.7%)
Gastritis	6/166 (3.6%)		8/165 (4.8%)
General disorders
Oedema peripheral	4/166 (2.4%)		7/165 (4.2%)
Oedema	2/166 (1.2%)		6/165 (3.6%)
Infections and infestations
Nasopharyngitis	54/166 (32.5%)		54/165 (32.7%)
Bronchitis	8/166 (4.8%)		2/165 (1.2%)
Pharyngitis	4/166 (2.4%)		6/165 (3.6%)
Injury, poisoning and procedural complications
Contusion	7/166 (4.2%)		5/165 (3%)
Fall	6/166 (3.6%)		5/165 (3%)
Investigations
Blood creatine phosphokinase increased	16/166 (9.6%)		15/165 (9.1%)
Brain natriuretic peptide increased	8/166 (4.8%)		6/165 (3.6%)
Blood pressure increased	0/166 (0%)		6/165 (3.6%)
Musculoskeletal and connective tissue disorders
Back pain	12/166 (7.2%)		8/165 (4.8%)
Arthralgia	2/166 (1.2%)		15/165 (9.1%)
Periarthritis	6/166 (3.6%)		5/165 (3%)
Pain in extremity	5/166 (3%)		4/165 (2.4%)
Nervous system disorders
Headache	5/166 (3%)		6/165 (3.6%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	13/166 (7.8%)		9/165 (5.5%)
Skin and subcutaneous tissue disorders
Eczema	7/166 (4.2%)		7/165 (4.2%)
Vascular disorders
Hypertension	6/166 (3.6%)		2/165 (1.2%)

Limitations/Caveats

331 participants were randomized in the core phase 2/3 thiazolidine (CCT-004) study and included in the Full Analysis Set in this study. 5 participants from CCT-004 study did not enter this study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.