Efficacy and Safety Study of Alogliptin and Insulin in the Treatment of Type 2 Diabetes.

Sponsor

Takeda (Industry)

Overall Status

Completed

CT.gov ID

NCT00286429

Collaborator

(none)

390

Enrollment

Locations

Arms

14.9

Duration (Months)

6.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy and safety of alogliptin, once daily (QD), taken in combination with insulin for the treatment of Type 2 Diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus	Drug: Alogliptin and insulin Drug: Alogliptin and insulin Drug: Insulin	Phase 3

Detailed Description

There are approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, of which 90% to 95% are type 2. The prevalence of type 2 diabetes varies among racial and ethnic populations and has been shown to correlate with age, obesity, family history, history of gestational diabetes, and physical inactivity. Over the next decade, a marked increase in the number of adults with diabetes mellitus is expected.

Takeda is developing alogliptin (SYR-322) for patients with type 2 diabetes mellitus. Alogliptin is an inhibitor of the dipeptidyl peptidase IV enzyme. Dipeptidyl peptidase 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 dipeptidyl peptidase IV will improve glycemic (glucose) control in patients with type 2 diabetes.

The aim of the current study is to evaluate the efficacy of alogliptin in combination with insulin in subjects who are inadequately controlled on insulin alone (with or without metformin). Individuals who participate in this study will be required to commit to a screening visit and up to 14 additional visits at the study center. Study participation is anticipated to be about 34 weeks (or 8.5 months).

Study Design

Study Type:

Interventional

Actual Enrollment :

390 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of SYR110322 (SYR-322) When Used in Combination With Insulin in Subjects With Type 2 Diabetes

Study Start Date :

Feb 1, 2006

Actual Primary Completion Date :

May 1, 2007

Actual Study Completion Date :

May 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Insulin	Drug: Insulin Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.
Experimental: Alogliptin 12.5 mg QD	Drug: Alogliptin and insulin Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks. Other Names: alogliptin SYR110322
Experimental: Alogliptin 25 mg QD	Drug: Alogliptin and insulin Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks. Other Names: alogliptin SYR110322

Arm

Intervention/Treatment

Placebo Comparator: Insulin

Drug: Insulin

Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.

Experimental: Alogliptin 12.5 mg QD

Drug: Alogliptin and insulin

Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.

Other Names:

alogliptin

SYR110322

Experimental: Alogliptin 25 mg QD

Drug: Alogliptin and insulin

Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.

Other Names:

alogliptin

SYR110322

Outcome Measures

Primary Outcome Measures

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26. [Baseline and Week 26.]
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 26 or final visit and glycosylated hemoglobin collected at baseline.

Secondary Outcome Measures

Change From Baseline in Glycosylated Hemoglobin (Week 4). [Baseline and Week 4.]
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 4 and Glycosylated Hemoglobin collected at baseline.
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.
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.
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.
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.
Change From Baseline in Fasting Plasma Glucose (Week 1). [Baseline and Week 1.]
The change between the value of fasting plasma glucose collected at final visit or week 1 and fasting plasma glucose collected at baseline.
Change From Baseline in Fasting Plasma Glucose (Week 2). [Baseline and Week 2.]
The change between the value of fasting plasma glucose collected at week 2 and fasting plasma glucose collected at baseline.
Change From Baseline in Fasting Plasma Glucose (Week 4). [Baseline and Week 4.]
The change between the value of fasting plasma glucose collected at week 4 and fasting plasma glucose collected at baseline.
Change From Baseline in Fasting Plasma Glucose (Week 8). [Baseline and Week 8.]
The change between the value of fasting plasma glucose collected at week 8 and fasting plasma glucose collected at baseline.
Change From Baseline in Fasting Plasma Glucose (Week 12). [Baseline and Week 12.]
The change between the value of fasting plasma glucose collected at week 12 and fasting plasma glucose collected at baseline.
Change From Baseline in Fasting Plasma Glucose (Week 16). [Baseline and Week 16.]
The change between the value of fasting plasma glucose collected at week 16 and fasting plasma glucose collected at baseline.
Change From Baseline in Fasting Plasma Glucose (Week 20). [Baseline and Week 20.]
The change between the value of fasting plasma glucose collected at week 20 and fasting plasma glucose collected at baseline.
Change From Baseline in Fasting Plasma Glucose (Week 26). [Baseline and Week 26.]
The change between the value of fasting plasma glucose collected at week 26 or final visit and fasting plasma glucose collected at baseline.
Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL). [26 Weeks.]
The number of participants with a fasting plasma glucose value greater than or equal to 200 mg per dL during the 26 week study.
Number of Participants Requiring Rescue. [26 Weeks.]
The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 26 week study.
Change From Baseline in C-peptide (Week 4). [Baseline and Week 4.]
The change between the value of C-peptide collected at week 4 and C-peptide collected at baseline.
Change From Baseline in C-peptide (Week 8). [Baseline and Week 8.]
The change between the value of C-peptide collected at week 8 and C-peptide collected at baseline.
Change From Baseline in C-peptide (Week 12). [Baseline and Week 12.]
The change between the value of C-peptide collected at week 12 and C-peptide collected at baseline.
Change From Baseline in C-peptide (Week 16). [Baseline and Week 16.]
The change between the value of C-peptide collected at week 16 and C-peptide collected at baseline.
Change From Baseline in C-peptide (Week 20). [Baseline and Week 20.]
The change between the value of C-peptide collected at week 20 and C-peptide collected at baseline.
Change From Baseline in C-peptide (Week 26). [Baseline and Week 26.]
The change between the value of C-peptide collected at week 26 or final visit and C-peptide collected at baseline.
Number of Participants With Glycosylated Hemoglobin ≤ 6.5%. [Baseline and Week 26.]
The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5% during the 26 week study.
Number of Participants With Glycosylated Hemoglobin ≤ 7.0%. [Baseline and Week 26.]
The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.0% during the 26 week study.
Number of Participants With Glycosylated Hemoglobin ≤ 7.5%. [Baseline and Week 26.]
The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.5% during the 26 week study.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%. [Baseline and Week 26.]
The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5% during the 26 week study.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%. [Baseline and Week 26.]
The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.0% during the 26 week study.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%. [Baseline and Week 26.]
The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.5% during the 26 week study.
Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%. [Baseline and Week 26.]
The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 2.0% during the 26 week study.
Change From Baseline in Body Weight (Week 8). [Baseline and Week 8.]
The change between Body Weight measured at week 8 and Body Weight measured at baseline.
Change From Baseline in Body Weight (Week 12). [Baseline and Week 12.]
The change between Body Weight measured at week 12 and Body Weight measured at baseline.
Change From Baseline in Body Weight (Week 20). [Baseline and Week 20.]
The change between Body Weight measured at week 20 and Body Weight measured at baseline.
Change From Baseline in Body Weight (Week 26). [Baseline and Week 26.]
The change between Body Weight measured at week 26 or final visit and Body Weight measured at baseline.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Diagnosis of type 2 diabetes mellitus and currently treated with insulin alone (with or without metformin), and is inadequately controlled. Metformin dose must be stable for at least 8 weeks prior to Randomization.
No treatment with antidiabetic agents other than insulin and metformin within the 8 weeks prior to Randomization.
Body mass index greater than or equal to 23 kg/m2 and less than or equal to 45 kg/m2
Fasting C-peptide concentration greater than or equal to 0.8 ng per mL. (If this screening criterion is not met, the subject still qualifies if C-peptide greater than or equal to 1.5 ng per mL after a challenge test).
Glycosylated hemoglobin concentration greater than or equal to 8.0% at Screening.
Using a stable dose of insulin of at least 15 units but not more than 100 units per day for at least 8 weeks prior to Randomization. A dose of insulin that varies by up to 15% of the mean will be considered as stable.
If regular use of other, non-excluded medications, must be on a stable dose for at least the 4 weeks prior to Screening. However, as needed use of prescription or over-the-counter medications is allowed at the discretion of the investigator.
Systolic blood pressure less than or equal to180 mm Hg and diastolic pressure less than or equal to 110 mm Hg
Hemoglobin greater than or equal to 12 g per dL for males and greater than or equal to10 g per dL for females.
Alanine aminotransferase less than or equal to 3 times the upper limit of normal.
Serum creatinine less than or equal to 2.0 mg per dL.
Thyroid-stimulating hormone level less than or equal to the upper limit of the normal range and the subject is clinically euthyroid.
Neither pregnant (confirmed by laboratory testing in females of childbearing potential) nor lactating.
Female subjects of childbearing potential must be practicing adequate contraception. Adequate contraception must be practiced for the duration of participation in the study.
Able and willing to monitor own blood glucose concentrations with a home glucose monitor
No major illness or debility that in the investigator's opinion prohibits the individual from completing the study
Able and willing to provide written informed consent

Exclusion Criteria

Urine albumin to creatinine ratio of greater than 1000 μg per mg at Screening. If elevated, the subject may be rescreened within 1 week.
History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years prior to Screening. (History of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed.).
History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
History of treated diabetic gastric paresis.
New York Heart Association Class III or IV heart failure regardless of therapy. Currently treated subjects who are stable at Class I or II are candidates for the study.
History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening.
History of any hemoglobinopathy that may affect determination of glycosylated hemoglobin.
History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.
History of a psychiatric disorder that will affect ability to participate in the study.
History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors.
History of alcohol or substance abuse within the 2 years prior to Screening.
Receipt of any investigational drug within the 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within the 3 months prior to Screening.
Prior treatment in an investigational study of alogliptin.
Excluded Medications:
Treatment with antidiabetic agents other than insulin and metformin is not allowed within the 8 weeks prior to Randomization and through the completion of the end-of treatment or early termination procedures. (Exception: if has received other antidiabetic therapy for less than 7 days within the 3 months prior to Screening.)
Treatment with weight-loss drugs, any investigational antidiabetics, or oral or systemically injected glucocorticoids is not allowed from 3 months prior to randomization through the completion of the end-of-treatment or early termination procedures. Inhaled corticosteroids are allowed.
Must not take any medications, including over-the-counter products, without first consulting with the investigator.

Contacts and Locations

Locations

	City	State	Country
1	Phoenix	Arizona	United States
2	Anaheim	California	United States
3	Artesia	California	United States
4	Fresno	California	United States
5	Mission Viejo	California	United States
6	Northridge	California	United States
7	Orange	California	United States
8	San Diego	California	United States
9	Tustin	California	United States
10	Walnut Creek	California	United States
11	Denver	Colorado	United States
12	Cocoa Beach	Florida	United States
13	Longwood	Florida	United States
14	New Port Richey	Florida	United States
15	Ocala	Florida	United States
16	St. Cloud	Florida	United States
17	Tampa	Florida	United States
18	Lawrenceville	Georgia	United States
19	Honolulu	Hawaii	United States
20	Avon	Indiana	United States
21	Evansville	Indiana	United States
22	Lafayette	Indiana	United States
23	St. Louis	Missouri	United States
24	Omaha	Nebraska	United States
25	Berlin	New Jersey	United States
26	Burlington	North Carolina	United States
27	Charlotte	North Carolina	United States
28	Hickory	North Carolina	United States
29	Morehead City	North Carolina	United States
30	Pinehurst	North Carolina	United States
31	Winston Salem	North Carolina	United States
32	Cincinnati	Ohio	United States
33	Tulsa	Oklahoma	United States
34	Medford	Oregon	United States
35	Lansdale	Pennsylvania	United States
36	Charleston	South Carolina	United States
37	Columbia	South Carolina	United States
38	Simpsonville	South Carolina	United States
39	Cookeville	Tennessee	United States
40	Corpus Christi	Texas	United States
41	Dallas	Texas	United States
42	San Antonio	Texas	United States
43	Temple	Texas	United States
44	Texarkana	Texas	United States
45	Burlington	Vermont	United States
46	Multiple Cities		Argentina
47	Multiple Cities		Australia
48	Multiple Cities		Brazil
49	Multiple Cities		Chile
50	Multiple Cities		Czech Republic
51	Multiple Cities		Germany
52	Multiple Cities		Guatemala
53	Multiple Cities		Hungary
54	Multiple Cities		India
55	Multiple Cities		Mexico
56	Multiple Cities		Netherlands
57	Multiple Cities		New Zealand
58	Multiple Cities		Peru
59	Multiple Cities		Poland
60	Multiple Cities		South Africa

Sponsors and Collaborators

Takeda

Investigators

Study Director: VP Biological Sciences, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Takeda

ClinicalTrials.gov Identifier:

NCT00286429

Other Study ID Numbers:

SYR-322-INS-011
2005-004671-38
U1111-1113-8369

First Posted:

Feb 3, 2006

Last Update Posted:

Feb 3, 2012

Last Verified:

Feb 1, 2012

Keywords provided by Takeda

Glucose Metabolism Disorder

Dysmetabolic Syndrome

Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details	Participants enrolled at 110 investigative sites in Australia, Brazil, Chile, Guatemala, Germany, Hungary, India, Mexico, New Zealand, the Netherlands, Poland, South Africa, and the United States from 16 March 2006 to 18 September 2006
Pre-assignment Detail	Participants with a historical diagnosis of type 2 diabetes mellitus who were inadequately controlled while being treated with insulin with or without metformin were enrolled in one of three, once-daily (QD) treatment groups.

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Period Title: Overall Study
STARTED	130	131	129
COMPLETED	55	83	77
NOT COMPLETED	75	48	52

Baseline Characteristics

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD	Total
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Total of all reporting groups
Overall Participants	130	131	129	390
Age, Customized (participants) [Number]
<65 years	109 83.8%	112 85.5%	106 82.2%	327 83.8%
≥65 years	21 16.2%	19 14.5%	23 17.8%	63 16.2%
Sex: Female, Male (Count of Participants)
Female	68 52.3%	76 58%	85 65.9%	229 58.7%
Male	62 47.7%	55 42%	44 34.1%	161 41.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26.
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 26 or final visit and glycosylated hemoglobin collected at baseline.
Time Frame	Baseline and Week 26.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF). ANCOVA = Analysis of covariance.

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	126	130	126
Least Squares Mean (Standard Error) [percentage of Glycosylated Hemoglobin]	-0.13 (0.077)	-0.63 (0.076)	-0.71 (0.078)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 26. For comparison of either alogliptin dose vs. placebo (2-sample t test), study sample size >=390 participants had 95% power to detect a treatment difference as small as 0.4% in the per protocol analysis set assuming a standard deviation of 0.8%, a 2-sided test at 0.05 significance level and >=80% of subjects meeting the per protocol criteria.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	A step-down strategy was used for the primary analysis. First, the 25mg dose was compared to placebo at the 2-sided 0.05 significance level. The 12.5 mg dose was compared to placebo only if the comparison of the 25mg dose to placebo was significant.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.51
	Confidence Interval	(2-Sided) 95% -0.72 to -0.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 26. For comparison of either alogliptin dose vs. placebo (2-sample t test), study sample size >=390 participants had 95% power to detect a treatment difference as small as 0.4% in the per protocol analysis set assuming a standard deviation of 0.8%, a 2-sided test at 0.05 significance level and >=80% of subjects meeting the per protocol criteria.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	A step-down strategy was used for the primary analysis. First, the 25mg dose was compared to placebo at the 2-sided 0.05 significance level. The 12.5 mg dose was compared to placebo only if the comparison of the 25mg dose to placebo was significant.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95% -0.80 to -0.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

2. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (Week 4).
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 4 and Glycosylated Hemoglobin collected at baseline.
Time Frame	Baseline and Week 4.

Outcome Measure Data

Analysis Population Description
Randomized participants who received at least 1 dose of study drug and who had an HbA1c measurement at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	114	116	116
Least Squares Mean (Standard Error) [percentage of Glycosylated Hemoglobin]	-0.26 (0.045)	-0.47 (0.045)	-0.58 (0.045)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95% -0.34 to -0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95% -0.45 to -0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

3. 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
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	126	130	126
Least Squares Mean (Standard Error) [percentage of Glycosylated Hemoglobin]	-0.27 (0.061)	-0.76 (0.060)	-0.84 (0.062)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95% -0.65 to -0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.56
	Confidence Interval	(2-Sided) 95% -0.73 to -0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

4. 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
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	126	130	126
Least Squares Mean (Standard Error) [percentage of Glycosylated Hemoglobin]	-0.27 (0.073)	-0.84 (0.072)	-0.81 (0.073)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95% -0.77 to -0.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) 95% -0.75 to -0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

5. 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
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	126	130	126
Least Squares Mean (Standard Error) [percentage of Glycosylated Hemoglobin]	-0.22 (0.076)	-0.80 (0.074)	-0.76 (0.076)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.58
	Confidence Interval	(2-Sided) 95% -0.79 to -0.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) 95% -0.75 to -0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

6. 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
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	126	130	126
Least Squares Mean (Standard Error) [percentage of Glycosylated Hemoglobin]	-0.17 (0.078)	-0.76 (0.076)	-0.74 (0.078)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95% -0.80 to -0.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in HbA1c at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and HbA1c).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95% -0.79 to -0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

7. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (Week 1).
Description	The change between the value of fasting plasma glucose collected at final visit or week 1 and fasting plasma glucose collected at baseline.
Time Frame	Baseline and Week 1.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 1. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	107	121	111
Least Squares Mean (Standard Error) [mg/dL]	6.3 (5.40)	-5.0 (5.07)	-9.9 (5.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 1. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.128
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-11.3
	Confidence Interval	(2-Sided) 95% -25.9 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 1. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.034
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-16.1
	Confidence Interval	(2-Sided) 95% -31.1 to -1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

8. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (Week 2).
Description	The change between the value of fasting plasma glucose collected at week 2 and fasting plasma glucose collected at baseline.
Time Frame	Baseline and Week 2.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 2. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	115	127	119
Least Squares Mean (Standard Error) [mg/dL]	1.0 (5.09)	-3.1 (4.84)	-11.4 (5.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 2. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.563
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) 95% -17.9 to 9.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 2. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.084
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.4
	Confidence Interval	(2-Sided) 95% -26.4 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

9. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (Week 4).
Description	The change between the value of fasting plasma glucose collected at week 4 and fasting plasma glucose collected at baseline.
Time Frame	Baseline and Week 4.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	119	128	120
Least Squares Mean (Standard Error) [mg/dL]	5.3 (5.28)	-5.0 (5.08)	-12.1 (5.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.160
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.3
	Confidence Interval	(2-Sided) 95% -24.7 to 4.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.020
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-17.4
	Confidence Interval	(2-Sided) 95% -32.1 to -2.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	124	131	126
Least Squares Mean (Standard Error) [mg/dL]	5.4 (5.42)	-13.5 (5.26)	-14.1 (5.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 8. The treatment effect was be evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.013
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-18.9
	Confidence Interval	(2-Sided) 95% -33.7 to -4.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.011
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-19.5
	Confidence Interval	(2-Sided) 95% -34.5 to -4.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	127	131	128
Least Squares Mean (Standard Error) [mg/dL]	-1.4 (5.47)	-5.2 (5.38)	-2.9 (5.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.624
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.8
	Confidence Interval	(2-Sided) 95% -18.9 to 11.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.853
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95% -16.7 to 13.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	127	131	128
Least Squares Mean (Standard Error) [mg/dL]	4.6 (5.38)	-5.3 (5.29)	-6.3 (5.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.190
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.9
	Confidence Interval	(2-Sided) 95% -24.7 to 4.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 16. The treatment effect was be evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.154
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.9
	Confidence Interval	(2-Sided) 95% -25.8 to 4.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	127	131	128
Least Squares Mean (Standard Error) [mg/dL]	8.6 (5.45)	-4.2 (5.36)	-11.3 (5.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.097
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.7
	Confidence Interval	(2-Sided) 95% -27.8 to 2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.010
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-19.9
	Confidence Interval	(2-Sided) 95% -35.1 to -4.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

14. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (Week 26).
Description	The change between the value of fasting plasma glucose collected at week 26 or final visit and fasting plasma glucose collected at baseline.
Time Frame	Baseline and Week 26.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	127	131	128
Least Squares Mean (Standard Error) [mg/dL]	5.8 (5.69)	2.3 (5.59)	-11.7 (5.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.662
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.5
	Confidence Interval	(2-Sided) 95% -19.2 to 12.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in FPG at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.030
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and FPG).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-17.6
	Confidence Interval	(2-Sided) 95% -33.4 to -1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

15. Secondary Outcome

Title	Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL).
Description	The number of participants with a fasting plasma glucose value greater than or equal to 200 mg per dL during the 26 week study.
Time Frame	26 Weeks.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 fasting plasma glucose measurement after baseline.

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	128	131	128
Number [participants]	105 80.8%	99 75.6%	86 66.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in number of participants with marked hyperglycemia. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.075
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.551
	Confidence Interval	(2-Sided) 95% 0.286 to 1.063
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) is alogliptin arm versus placebo. OR <1.0 indicates lower incidence compared to placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in number of participants with marked hyperglycemia. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.002
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.364
	Confidence Interval	(2-Sided) 95% 0.191 to 0.695
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) is alogliptin arm versus placebo. OR <1.0 indicates lower incidence compared to placebo.

16. Secondary Outcome

Title	Number of Participants Requiring Rescue.
Description	The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 26 week study.
Time Frame	26 Weeks.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who completed at least 1 study visit after baseline.

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	129	131	128
Number [participants]	52 40%	27 20.6%	25 19.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in number of participants requiring rescue. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.350
	Confidence Interval	(2-Sided) 95% 0.198 to 0.619
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) is alogliptin arm versus placebo arm. OR <1.0 indicates lower incidence compared to placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in number of participants requiring rescue. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.339
	Confidence Interval	(2-Sided) 95% 0.189 to 0.608
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) is alogliptin arm versus placebo. OR <1.0 indicates lower incidence compared to placebo.

17. Secondary Outcome

Title	Change From Baseline in C-peptide (Week 4).
Description	The change between the value of C-peptide collected at week 4 and C-peptide collected at baseline.
Time Frame	Baseline and Week 4.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 4. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	99	111	109
Least Squares Mean (Standard Error) [ng/mL]	-0.023 (0.1062)	0.132 (0.1001)	0.453 (0.1014)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-Peptide at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.286
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.156
	Confidence Interval	(2-Sided) 95% -0.131 to 0.443
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 4. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.001
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	.477
	Confidence Interval	(2-Sided) 95% 0.188 to 0.765
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

18. Secondary Outcome

Title	Change From Baseline in C-peptide (Week 8).
Description	The change between the value of C-peptide collected at week 8 and C-peptide collected at baseline.
Time Frame	Baseline and Week 8.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	121	130	123
Least Squares Mean (Standard Error) [ng/mL]	-0.024 (0.1224)	0.178 (0.1180)	0.348 (0.1220)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-Peptide at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.236
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.202
	Confidence Interval	(2-Sided) 95% -0.132 to 0.536
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-Peptide at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.032
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.372
	Confidence Interval	(2-Sided) 95% 0.032 to 0.712
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

19. Secondary Outcome

Title	Change From Baseline in C-peptide (Week 12).
Description	The change between the value of C-peptide collected at week 12 and C-peptide collected at baseline.
Time Frame	Baseline and Week 12.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	124	130	126
Least Squares Mean (Standard Error) [ng/mL]	0.207 (0.1558)	0.333 (0.1521)	0.390 (0.1553)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.562
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.126
	Confidence Interval	(2-Sided) 95% -0.302 to 0.554
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.407
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.183
	Confidence Interval	(2-Sided) 95% -0.251 to 0.616
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

20. Secondary Outcome

Title	Change From Baseline in C-peptide (Week 16).
Description	The change between the value of C-peptide collected at week 16 and C-peptide collected at baseline.
Time Frame	Baseline and Week 16.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 16. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	124	130	126
Least Squares Mean (Standard Error) [ng/mL]	0.241 (0.1536)	0.319 (0.1500)	0.396 (0.1532)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.716
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.078
	Confidence Interval	(2-Sided) 95% -0.344 to 0.500
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 16. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.474
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.156
	Confidence Interval	(2-Sided) 95% -0.272 to 0.583
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

21. Secondary Outcome

Title	Change From Baseline in C-peptide (Week 20).
Description	The change between the value of C-peptide collected at week 20 and C-peptide collected at baseline.
Time Frame	Baseline and Week 20.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	124	130	126
Least Squares Mean (Standard Error) [ng/mL]	0.239 (0.1467)	0.318 (0.1432)	0.281 (0.1463)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.700
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.079
	Confidence Interval	(2-Sided) 95% -0.324 to 0.482
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.839
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.042
	Confidence Interval	(2-Sided) 95% -0.366 to 0.450
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

22. Secondary Outcome

Title	Change From Baseline in C-peptide (Week 26).
Description	The change between the value of C-peptide collected at week 26 or final visit and C-peptide collected at baseline.
Time Frame	Baseline and Week 26.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	124	130	126
Least Squares Mean (Standard Error) [ng/mL]	-0.083 (0.1192)	0.199 (0.1164)	0.042 (0.1189)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.091
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.282
	Confidence Interval	(2-Sided) 95% -0.045 to 0.610
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in C-peptide at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.459
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and C-peptide).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.125
	Confidence Interval	(2-Sided) 95% -0.207 to 0.457
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

23. Secondary Outcome

Title	Number of Participants With Glycosylated Hemoglobin ≤ 6.5%.
Description	The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5% during the 26 week study.
Time Frame	Baseline and Week 26.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who completed at least 1 HbA1c measurement after baseline. Due to no participants in the placebo arm achieved HbA1c ≤ 6.5%, the odds ratio of alogliptin to placebo and 95% CI were not estimable from the logistic regression.

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	129	131	129
Number [participants]	0 0%	3 2.3%	3 2.3%

24. Secondary Outcome

Title	Number of Participants With Glycosylated Hemoglobin ≤ 7.0%.
Description	The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.0% during the 26 week study.
Time Frame	Baseline and Week 26.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	129	131	129
Number [participants]	1 0.8%	11 8.4%	10 7.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c ≤7.0%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.016
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	12.650
	Confidence Interval	(2-Sided) 95% 1.589 to 100.682
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c ≤7.0%. The treatment effect was evaluated as a contrast of each active dose versus placebo was evaluated inferentially with a Wald test at the 0.05 significance level
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.023
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	11.255
	Confidence Interval	(2-Sided) 95% 1.401 to 90.379
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.

25. Secondary Outcome

Title	Number of Participants With Glycosylated Hemoglobin ≤ 7.5%.
Description	The number of participants with a value for the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) less than or equal to 7.5% during the 26 week study.
Time Frame	Baseline and Week 26.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	129	131	129
Number [participants]	5 3.8%	22 16.8%	33 25.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c ≤7.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.777
	Confidence Interval	(2-Sided) 95% 2.047 to 16.305
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c ≤7.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	9.784
	Confidence Interval	(2-Sided) 95% 3.540 to 27.039
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.

26. Secondary Outcome

Title	Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%.
Description	The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5% during the 26 week study.
Time Frame	Baseline and Week 26.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	129	131	129
Number [participants]	40 30.8%	70 53.4%	70 54.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥0.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.674
	Confidence Interval	(2-Sided) 95% 1.579 to 4.530
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥0.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.819
	Confidence Interval	(2-Sided) 95% 1.653 to 4.808
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.

27. Secondary Outcome

Title	Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%.
Description	The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.0% during the 26 week study.
Time Frame	Baseline and Week 26.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	129	131	129
Number [participants]	17 13.1%	41 31.3%	47 36.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥1.0%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.163
	Confidence Interval	(2-Sided) 95% 1.651 to 6.060
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥1.0%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.989
	Confidence Interval	(2-Sided) 95% 2.083 to 7.640
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.

28. Secondary Outcome

Title	Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%.
Description	The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 1.5% during the 26 week study.
Time Frame	Baseline and Week 26.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline.

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	129	131	129
Number [participants]	6 4.6%	22 16.8%	23 17.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥1.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.002
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.550
	Confidence Interval	(2-Sided) 95% 1.732 to 11.953
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no treatment effect between alogliptin and placebo arms in incidence of HbA1c decrease from baseline ≥1.5%. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a Wald test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.002
	Comments	No multiplicity adjustments.
	Method	Regression, Logistic
	Comments	Logistic regression model includes effects for treatment, geographic region, baseline metformin regimen, baseline insulin dose, and baseline HbA1c.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.580
	Confidence Interval	(2-Sided) 95% 1.740 to 12.052
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio (OR) compares alogliptin arm versus placebo. OR >1.0 indicates higher incidence of response compared to placebo.

29. Secondary Outcome

Title	Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%.
Description	The number of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 2.0% during the 26 week study.
Time Frame	Baseline and Week 26.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had at least 1 HbA1c measurement after baseline. Due to no participants in the placebo arm achieved HbA1c decrease from baseline ≥2.0%, the odds ratio of alogliptin to placebo and 95% CI were not estimable from the logistic regression.

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	129	131	129
Number [participants]	0 0%	11 8.4%	11 8.5%

30. Secondary Outcome

Title	Change From Baseline in Body Weight (Week 8).
Description	The change between Body Weight measured at week 8 and Body Weight measured at baseline.
Time Frame	Baseline and Week 8.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 8. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	118	125	121
Least Squares Mean (Standard Error) [kg]	0.39 (0.191)	0.10 (0.185)	0.18 (0.189)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.291
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95% -0.81 to 0.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 8. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.439
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95% -0.74 to 0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

31. Secondary Outcome

Title	Change From Baseline in Body Weight (Week 12).
Description	The change between Body Weight measured at week 12 and Body Weight measured at baseline.
Time Frame	Baseline and Week 12.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 12. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	121	127	123
Least Squares Mean (Standard Error) [kg]	0.50 (0.221)	0.44 (0.215)	0.31 (0.219)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.841
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95% -0.67 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 12. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.556
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95% -0.80 to 0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

32. Secondary Outcome

Title	Change From Baseline in Body Weight (Week 20).
Description	The change between Body Weight measured at week 20 and Body Weight measured at baseline.
Time Frame	Baseline and Week 20.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 20. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	121	127	124
Least Squares Mean (Standard Error) [kg]	0.73 (0.231)	0.55 (0.225)	0.45 (0.229)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.586
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95% -0.81 to 0.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 20. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.404
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95% -0.91 to 0.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

33. Secondary Outcome

Title	Change From Baseline in Body Weight (Week 26).
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.

Outcome Measure Data

Analysis Population Description
Randomized subjects who received at least 1 dose of study drug (Full Analysis Set), and who had measurements at baseline and at Week 26. Missing data are imputed using last observation carried forward (LOCF).

Arm/Group Title	Placebo	Alogliptin 12.5 mg QD	Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.	Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
Measure Participants	121	127	124
Least Squares Mean (Standard Error) [kg]	0.63 (0.244)	0.68 (0.237)	0.60 (0.241)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 12.5 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.874
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95% -0.62 to 0.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Alogliptin 25 mg QD
	Comments	The null hypothesis that there is no difference between alogliptin and placebo arms in change from baseline in body weight at Week 26. The treatment effect was evaluated as a contrast of each active dose versus placebo and was evaluated inferentially with a 2-sided t test at the 0.05 significance level.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.948
	Comments	No multiplicity adjustments.
	Method	ANCOVA
	Comments	ANCOVA included treatment, geographic region, and baseline metformin regimen as class variables, and baseline covariates (insulin dose and weight).

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95% -0.70 to 0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Negative mean treatment difference indicates larger decrease from baseline (more negative change from baseline) in the alogliptin arm compared to the placebo arm.

Adverse Events

	Placebo		Alogliptin 12.5 mg QD		Alogliptin 25 mg QD
Time Frame	Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious event) after the last dose of double-blind 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 was recorded, irrespective of the relation to study treatment.

Arm/Group Title	Placebo		Alogliptin 12.5 mg QD		Alogliptin 25 mg QD
Arm/Group Description	Alogliptin placebo-matching tablets, orally, once daily and insulin for up to 26 weeks.		Alogliptin 12.5 mg, tablets, orally, once daily and insulin for up to 26 weeks.		Alogliptin 25 mg, tablets, orally, once daily and insulin for up to 26 weeks.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Alogliptin 12.5 mg QD		Alogliptin 25 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/129 (4.7%)		8/131 (6.1%)		7/129 (5.4%)
Cardiac disorders
Angina unstable	1/129 (0.8%)		0/131 (0%)		1/129 (0.8%)
Atrial fibrillation	0/129 (0%)		2/131 (1.5%)		0/129 (0%)
Coronary artery disease	0/129 (0%)		1/131 (0.8%)		0/129 (0%)
Gastrointestinal disorders
Diverticulitis intestinal haemorrhagic	1/129 (0.8%)		0/131 (0%)		0/129 (0%)
Pancreatitis	0/129 (0%)		1/131 (0.8%)		0/129 (0%)
Upper gastrointestinal haemorrhage	0/129 (0%)		0/131 (0%)		1/129 (0.8%)
General disorders
Sudden death	0/129 (0%)		1/131 (0.8%)		0/129 (0%)
Hepatobiliary disorders
Cholecystitis	0/129 (0%)		2/131 (1.5%)		0/129 (0%)
Immune system disorders
Hypersensitivity	0/129 (0%)		0/131 (0%)		1/129 (0.8%)
Infections and infestations
Pyelonephritis	0/129 (0%)		0/131 (0%)		1/129 (0.8%)
Scrotal abscess	0/129 (0%)		1/131 (0.8%)		0/129 (0%)
Staphylococcal infection	0/129 (0%)		0/131 (0%)		1/129 (0.8%)
Injury, poisoning and procedural complications
Incisional hernia	1/129 (0.8%)		0/131 (0%)		0/129 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/129 (0%)		0/131 (0%)		1/129 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma	1/129 (0.8%)		0/131 (0%)		0/129 (0%)
Nervous system disorders
Demyelination	1/129 (0.8%)		0/131 (0%)		0/129 (0%)
Hypoglycaemic coma	0/129 (0%)		0/131 (0%)		1/129 (0.8%)
Ischaemic stroke	1/129 (0.8%)		0/131 (0%)		0/129 (0%)
Sciatica	0/129 (0%)		1/131 (0.8%)		0/129 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Alogliptin 12.5 mg QD		Alogliptin 25 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/129 (41.9%)		58/131 (44.3%)		50/129 (38.8%)
Gastrointestinal disorders
Abdominal pain	1/129 (0.8%)		1/131 (0.8%)		6/129 (4.7%)
Diarrhoea	7/129 (5.4%)		1/131 (0.8%)		8/129 (6.2%)
Nausea	3/129 (2.3%)		4/131 (3.1%)		6/129 (4.7%)
Vomiting	4/129 (3.1%)		0/131 (0%)		3/129 (2.3%)
General disorders
Oedema peripheral	4/129 (3.1%)		4/131 (3.1%)		7/129 (5.4%)
Infections and infestations
Bronchitis	4/129 (3.1%)		3/131 (2.3%)		1/129 (0.8%)
Influenza	3/129 (2.3%)		4/131 (3.1%)		3/129 (2.3%)
Nasopharyngitis	6/129 (4.7%)		5/131 (3.8%)		8/129 (6.2%)
Upper respiratory tract	4/129 (3.1%)		6/131 (4.6%)		4/129 (3.1%)
Urinary tract infection	10/129 (7.8%)		8/131 (6.1%)		9/129 (7%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	3/129 (2.3%)		5/131 (3.8%)		2/129 (1.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/129 (2.3%)		9/131 (6.9%)		3/129 (2.3%)
Back pain	2/129 (1.6%)		2/131 (1.5%)		6/129 (4.7%)
Nervous system disorders
Dizziness	2/129 (1.6%)		5/131 (3.8%)		1/129 (0.8%)
Headache	6/129 (4.7%)		7/131 (5.3%)		4/129 (3.1%)
Psychiatric disorders
Insomnia	0/129 (0%)		4/131 (3.1%)		1/129 (0.8%)
Respiratory, thoracic and mediastinal disorders
Cough	4/129 (3.1%)		2/131 (1.5%)		2/129 (1.6%)
Skin and subcutaneous tissue disorders
Pruritus	0/129 (0%)		0/131 (0%)		4/129 (3.1%)
Vascular disorders
Hypertension	6/129 (4.7%)		5/131 (3.8%)		2/129 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.

Results Point of Contact

Name/Title	Sr. VP, Clinical Science
Organization	Takeda Global Research and Development Center, Inc.
Phone	800-778-2860
Email	clinicaltrialregistry@tpna.com

Responsible Party:

Takeda

ClinicalTrials.gov Identifier:

NCT00286429

Other Study ID Numbers:

SYR-322-INS-011
2005-004671-38
U1111-1113-8369

First Posted:

Feb 3, 2006

Last Update Posted:

Feb 3, 2012

Last Verified:

Feb 1, 2012