A Study Assessing Saxagliptin Treatment in Type 2 Diabetic Subjects Who Are Not Controlled With TZD Therapy Alone

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00295633
• Collaborator: (none)
• Enrollment: 565
• Locations: 133
• Arms: 3
• Duration (Months): 31
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this clinical research study is to learn whether Saxagliptin added to thiazolidinedione (TZD) therapy is more effective than TZD alone as a treatment for Type 2 diabetic subjects who are not sufficiently controlled with TZD alone

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Saxagliptin; Drug: Saxagliptin; Drug: Placebo; Drug: pioglitazone; Drug: rosiglitazone; Drug: metformin	Phase 3

Detailed Description

All subjects will participate in a lead-in period, and qualifying subjects will continue into a short-term randomized treatment period. Subjects who complete the short-term period will be eligible to enter the long term extension period. Also, subjects in the short-term period who have an elevated blood sugar that requires additional medication for blood sugar control will be eligible to enter the long-term treatment extension period where they will receive metformin (defined as rescue medication) added onto their blinded study medication

Study Design

• Study Type: Interventional
• Actual Enrollment: 565 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double Blind, Placebo Controlled, Phase III Trial to Evaluate the Efficacy and Safety of Saxagliptin (BMS477118) in Combination With Thiazolidinedione Therapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Thiazolidinedione Therapy Alone
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Oct 1, 2007
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Saxagliptin plus open-label TZD (A) Saxagliptin PLUS pioglitazone OR rosiglitazone PLUS open-label metformin (as needed as rescue medication)	Drug: Saxagliptin; Tablets, Oral, 2.5 mg, Once daily (6 months ST, 12 months LT); Other Names: BMS-477118 ; Drug: pioglitazone; Tablets, Oral, 30 mg or 45 mg, once daily (6 months ST, 12 months LT); Drug: rosiglitazone; Tablets, Oral, 4 mg, once daily or 8 mg, either as once or twice daily (6 months ST, 12 months LT); Drug: metformin; Tablets, Oral, 500-2500 mg, as needed (12 months LT)
Experimental: Saxagliptin plus open-label TZD (B) Saxagliptin PLUS pioglitazone OR rosiglitazone PLUS open-label metformin (as needed as rescue medication)	Drug: Saxagliptin; Tablets, Oral, 5 mg, once daily (6 months ST, 12 months LT); Other Names: BMS-477118 ; Drug: pioglitazone; Tablets, Oral, 30 mg or 45 mg, once daily (6 months ST, 12 months LT); Drug: rosiglitazone; Tablets, Oral, 4 mg, once daily or 8 mg, either as once or twice daily (6 months ST, 12 months LT); Drug: metformin; Tablets, Oral, 500-2500 mg, as needed (12 months LT)
Placebo Comparator: Placebo plus open-label TZD (C) Placebo PLUS pioglitazone OR rosiglitazone PLUS open-label metformin (as needed as rescue medication)	Drug: Placebo; Tablets, Oral, 0 mg, Once daily (6 months ST, 12 months LT); Drug: pioglitazone; Tablets, Oral, 30 mg or 45 mg, once daily (6 months ST, 12 months LT); Drug: rosiglitazone; Tablets, Oral, 4 mg, once daily or 8 mg, either as once or twice daily (6 months ST, 12 months LT); Drug: metformin; Tablets, Oral, 500-2500 mg, as needed (12 months LT)

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Hemoglobin A1c (A1C) at Week 24 [Baseline, Week 24]

   Mean change from baseline in A1C at Week 24, adjusted for baseline value.

Secondary Outcome Measures

1. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 [Baseline, Week 24]

   Mean change from baseline in FPG at Week 24, adjusted for baseline value.

2. Percentage of Participants Achieving A1c <7% at Week 24 [Week 24]

   Percentage of participants achieving A1C < 7%, the American Diabetic Association's defined goal for glycemia, at each dose of saxagliptin plus TZD versus placebo plus TZD at Week 24.

3. Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 [Baseline, Week 24]

   Mean change from baseline for 0 to 180 minutes PPG AUC achieved at each dose of saxagliptin plus TZD versus placebo plus TZD at Week 24, adjusted for baseline value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 77 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetics currently receiving a stable dose of TZD monotherapy (pioglitazone 30mg or 45mg, or rosiglitazone 4mg or 8mg) for at least 12 weeks prior to screening.

• Hemoglobin A1c (HbA1c) > = 7.0% and < = 10.5%

• Body mass index < = 45kg/m2

• Fasting C-peptide > = 1 ng/mL

Exclusion Criteria:

• Symptomatic poorly controlled diabetes

• Recent cardiac or cerebrovascular event

• Serum creatinine > = 2.0 mg/dL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Winston Technology, Inc.	Haleyville	Alabama	United States	35565
2	Sunbelt Research Group, Llc	Mobile	Alabama	United States	36606
3	Iicr, Inc.	Ozark	Alabama	United States	36360
4	Clinical Research Advantage, Inc	Mesa	Arizona	United States	85213
5	Nea Clinic	Jonesboro	Arkansas	United States	72401
6	Little Rock Family Practice Clinic	Little Rock	Arkansas	United States	72205
7	Impact Clinical Trials	Beverly Hills	California	United States	90211
8	Lovelace Scientific Resources, Inc.	Beverly Hills	California	United States	90211
9	Medical Group Of Encino	Encino	California	United States	91436
10	Marin Endocrine Care And Research, Inc.	Greenbrae	California	United States	94904
11	Del Rosario Medical Clinic, Inc.	Huntington Park	California	United States	90255
12	Loma Linda Va Healthcare Systems	Loma Linda	California	United States	92357
13	Peak Health Medical Group	Los Angeles	California	United States	90025
14	Richard Cherlin, Md	Los Gatos	California	United States	95032
15	Mission Internal Medical Group	Mission Viejo	California	United States	92691
16	Desert Medical Advances	Palm Desert	California	United States	92260
17	Denver Internal Medicine Group	Denver	Colorado	United States	80209
18	Stamford Therapeutics Consortium	Stamford	Connecticut	United States	06905
19	Phoenix Internal Medicine Associates, Llc	Waterbury	Connecticut	United States	06708
20	Central Florida Clinical Trials, Inc.	Altamonte Springs	Florida	United States	32714
21	Southern Family Healthcare, Pa	Chipley	Florida	United States	32428
22	Doctors Medical Center Of Walton County	Defuniak Springs	Florida	United States	32435
23	Horizon Institute For Clinical Research	Hollywood	Florida	United States	33021
24	Jacksonville Center For Clinical Research	Jacksonville	Florida	United States	32205
25	Panhandle Family Care Associates	Marianna	Florida	United States	32446
26	Nextphase Clinical Trials, Inc	Miami	Florida	United States	33145
27	Baptist Diabetes Associates	Miami	Florida	United States	33156
28	Heart & Vascular Center Research, Inc.	Sarasota	Florida	United States	34239
29	Alan B. Miller, Md	Dunwoody	Georgia	United States	30338
30	Marietta Clinical Research, Inc.	Marietta	Georgia	United States	30060
31	Endocrine Research Solutions, Inc.	Roswell	Georgia	United States	30076
32	D. Thomas Rogers, Md, Facs	Kahului	Hawaii	United States	96732
33	Southeast Idaho Family Practice	Idaho Falls	Idaho	United States	83404
34	Cedar-Crosse Research Center	Chicago	Illinois	United States	60607
35	Physicians Research Group	Indianapolis	Indiana	United States	46250
36	Northwest Indiana Center For Clinical Research	Valparaiso	Indiana	United States	46383
37	Lipid Research Clinic	Iowa City	Iowa	United States	52242
38	Professional Research Network Of Kansas	Wichita	Kansas	United States	67203
39	Mouhaffel, Assad H.	West Monroe	Louisiana	United States	71291
40	Promed Physicians Family Practice	Portage	Michigan	United States	49024
41	Olive Branch Family Medical Center	Olive Branch	Mississippi	United States	38654
42	Radiant Research Las Vegas	Las Vegas	Nevada	United States	89146
43	Nevada Alliance Against Diabetes	North Las Vegas	Nevada	United States	89030
44	Office Of Ammar Bazerbashi, Md	Holmdel	New Jersey	United States	07733
45	Urgentmed, P.C.	South Bound Brook	New Jersey	United States	08880
46	Medical Research Associates Of Charlotte, Inc.	Charlotte	North Carolina	United States	28211
47	Carolina Pharmaceutical Research	Statesville	North Carolina	United States	28625
48	Community Health Care	Canal Fulton	Ohio	United States	44614
49	Clinical Research Limited	Canton	Ohio	United States	44718
50	Rapid Medical Research, Inc.	Cleveland	Ohio	United States	44122
51	Providence Health Partners - Center For Clinical Research	Dayton	Ohio	United States	45439
52	Holzer Clinic	Gallipolis	Ohio	United States	45631
53	Wells Institute For Health Awareness	Kettering	Ohio	United States	45429
54	David Witkin, Md	Eugene	Oregon	United States	97401
55	Harleysville Medical Associates	Harleysville	Pennsylvania	United States	19438
56	Family Medical Associates	Levittown	Pennsylvania	United States	19056
57	Banksville Medical Pc	Pittsburgh	Pennsylvania	United States	15216
58	Three Rivers Medical Associates, Pa	Columbia	South Carolina	United States	29201
59	Radiant Research, Greer	Greer	South Carolina	United States	29651
60	Upstate Pharmaceutical Research	Simpsonville	South Carolina	United States	29681
61	East Tennessee Medical Group	Alcoa	Tennessee	United States	37701
62	Healthstar Physicians	Morristown	Tennessee	United States	37813
63	Hayes Endocrine And Diabetes Center	Nashville	Tennessee	United States	37209
64	Capital Medical Clinic, Llp	Austin	Texas	United States	78705
65	Texas Diabetes And Endocrinology, P.A.	Austin	Texas	United States	78731
66	Radiant Research-Austin	Austin	Texas	United States	78752
67	Priscilla Hollander, Md, Phd	Dallas	Texas	United States	75246
68	The Medical Group Of Texas	Fort Worth	Texas	United States	76104
69	Mobley Research Center	Houston	Texas	United States	77024
70	Family Physician, Pa	Houston	Texas	United States	77074
71	Mapleridge Medical Center	Houston	Texas	United States	77081
72	Diabetes Center Of The Southwest	Midland	Texas	United States	79705
73	Pearland Primary Care Associates, Llp	Pearland	Texas	United States	77584
74	Med-Cure	Rosenberg	Texas	United States	77471
75	Radiant Research San Antonio	San Antonio	Texas	United States	78229
76	S.A.M. Clinical Research Center	San Antonio	Texas	United States	78229
77	Collom And Carney Clinic	Texarkana	Texas	United States	75503
78	National Clinical Research, Inc.	Richmond	Virginia	United States	23294
79	Tidewater Integrated Medical Research	Virginia Beach	Virginia	United States	23451
80	Local Institution	Belgrano	Buenos Aires	Argentina	C1426EGP
81	Local Institution	Chacabuco	Buenos Aires	Argentina	B6740CWC
82	Local Institution	Ciudad Auton.	Buenos Aires	Argentina	C1505CWB
83	Local Institution	La Plata	Buenos Aires	Argentina	1900
84	Local Institution	Moron	Buenos Aires	Argentina	B17081FF
85	Local Institution	Ciudad De Mendoza	Mendoza	Argentina	M5519XAC
86	Local Institution	Rosario	Santa Fe	Argentina	S2000CVD
87	Local Institution	Lanus Este	Tucuman	Argentina	1824
88	Local Institution	Buenos Aires		Argentina	C1408INH
89	Local Institution	Buenos Aires		Argentina	C1425AGC
90	Local Institution	St. Johns	Newfoundland and Labrador	Canada	A1E 2C2
91	Local Institution	Halifax	Nova Scotia	Canada	B3H 2Y9
92	Local Institution	Sarnia	Ontario	Canada	N7T 4X3
93	Local Institution	St Catharines	Ontario	Canada	L2R 7P3
94	Local Institution	St-Leonard	Quebec	Canada	H1S 3A9
95	Local Institution	Ste-Foy	Quebec	Canada	G1V 4G2
96	Local Institution	Saskatoon	Saskatchewan	Canada	S7K 3H3
97	Local Institution	Bangalore		India	560010
98	Local Institution	Bangalore		India	560054
99	Local Institution	Chennai		India	600010
100	Local Institution	Chennai		India	600013
101	Local Institution	Chennai		India	600086
102	Local Institution	Chennai		India	680004
103	Local Institution	Hariyana		India	132001
104	Local Institution	Hyderabad		India	500082
105	Local Institution	Indore		India	452001
106	Local Institution	Maharashtra		India	411011
107	Local Institution	Mangalore		India	575001
108	Local Institution	Mumbai		India	400021
109	Local Institution	Mumbai		India	400067
110	Local Institution	Pune		India	411011
111	Local Institution	Vellore		India	632004
112	Local Institution	Chichuahua	Chihuahua	Mexico	31000
113	Local Institution	Angeles Del Pedregal	Distrito Federal	Mexico	10700
114	Local Institution	Zapopan	Jalisco	Mexico	45200
115	Local Institution	Michoacan	Morelos	Mexico	58000
116	Local Institution	Monterrey	Nuevo Leon	Mexico	66260
117	Local Institution	Aguascalientes		Mexico	20232
118	Local Institution	Cercado De Lima	Lima	Peru	1
119	Local Institution	La Victoria	Lima	Peru	13
120	Local Institution	Miraflores	Lima	Peru	18
121	Local Institution	San Isidro	Lima	Peru	27
122	Local Institution	San Martin De Porres	Lima	Peru	31
123	Local Institution	Santiago De Surco	Lima	Peru	33
124	Local Institution	Cebu City		Philippines	1600
125	Local Institution	Cebu City		Philippines	6000
126	Local Institution	Iloilo City		Philippines	5000
127	Local Institution	Las Pinas		Philippines	1740
128	Local Institution	Pasig City		Philippines	1600
129	Local Institution	Carolina		Puerto Rico	00983
130	Local Institution	Ponce		Puerto Rico	00716
131	Local Institution	Ponce		Puerto Rico	00717
132	Local Institution	Rio Piedras		Puerto Rico	00926
133	Local Institution	San Juan		Puerto Rico	00920

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

• Hollander P, Li J, Allen E, Chen R; CV181-013 Investigators. Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone. J Clin Endocrinol Metab. 2009 Dec;94(12):4810-9. doi: 10.1210/jc.2009-0550. Epub 2009 Oct 28.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00295633
• Other Study ID Numbers: CV181-013
• First Posted: Feb 24, 2006
• Last Update Posted: Apr 7, 2015
• Last Verified: Mar 1, 2015

• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Metformin; Pioglitazone; Rosiglitazone; Saxagliptin

Study Results

Participant Flow

Arm/Group Title	Saxagliptin 2.5 mg Plus Open-label Thiazolidinedione (TZD)	Saxagliptin 5 mg Plus Open-label TZD	Placebo Plus Open-label TZD
Arm/Group Description	The Saxagliptin 2.5 mg + Open-Label TZD group includes data from subjects randomized to receive coadministration of blinded Saxagliptin 2.5 mg plus open-label pioglitazone 30 mg or 45 mg once daily (QD), or open label rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	The Saxagliptin 5 mg + Open-Label TZD group includes data from subjects randomized to receive coadministration of blinded Saxagliptin 5 mg plus pioglitazone 30 mg or 45 mg once daily (QD), or rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	The placebo + open-label TZD group includes data from subjects randomized to receive coadministration of blinded placebo plus pioglitazone 30 mg or 45 mg once daily (QD), or rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.
Period Title: Overall Study
STARTED	195	186	184
Completed Study Without Being Rescued	88	82	51
COMPLETED	133	119	108
NOT COMPLETED	62	67	76

Baseline Characteristics

Arm/Group Title	Saxagliptin 2.5 mg Plus Open-label TZD	Saxagliptin 5 mg Plus Open-label TZD	Placebo Plus Open-label TZD	Total
Arm/Group Description	The Saxagliptin 2.5 mg + Open-Label TZD group includes data from subjects randomized to receive coadministration of blinded Saxagliptin 2.5 mg plus open-label pioglitazone 30 mg or 45 mg once daily (QD), or open label rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	The Saxagliptin 5 mg + Open-Label TZD group includes data from subjects randomized to receive coadministration of blinded Saxagliptin 5 mg plus pioglitazone 30 mg or 45 mg once daily (QD), or rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	The placebo + open-label TZD group includes data from subjects randomized to receive coadministration of blinded placebo plus pioglitazone 30 mg or 45 mg once daily (QD), or rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	Total of all reporting groups
Overall Participants	195	186	184	565
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.85 (9.73)	53.22 (10.56)	54.01 (10.08)	54.04 (10.13)
Sex: Female, Male (Count of Participants)
Female	89 45.6%	97 52.2%	99 53.8%	285 50.4%
Male	106 54.4%	89 47.8%	85 46.2%	280 49.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hemoglobin A1c (A1C) at Week 24
Description	Mean change from baseline in A1C at Week 24, adjusted for baseline value.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 Last Observation Carried Forward (LOCF), participants must have had a baseline and at least 1 post-baseline measurement. If participant received rescue medication, measurement must have been taken before rescue.

Arm/Group Title	Saxagliptin 2.5 mg Plus Open-label TZD	Saxagliptin 5 mg Plus Open-label TZD	Placebo Plus Open-label TZD
Arm/Group Description	The Saxagliptin 2.5 mg + Open-Label TZD group includes data from subjects randomized to receive coadministration of blinded Saxagliptin 2.5 mg plus open-label pioglitazone 30 mg or 45 mg once daily (QD), or open label rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	The Saxagliptin 5 mg + Open-Label TZD group includes data from subjects randomized to receive coadministration of blinded Saxagliptin 5 mg plus pioglitazone 30 mg or 45 mg once daily (QD), or rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	The placebo + open-label TZD group includes data from subjects randomized to receive coadministration of blinded placebo plus pioglitazone 30 mg or 45 mg once daily (QD), or rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.
Measure Participants	192	183	180
Baseline Mean	8.25 (0.080)	8.35 (0.080)	8.19 (0.080)
Week 24 Mean	7.59 (0.098)	7.39 (0.086)	7.91 (0.100)
Adjusted Mean Change from Baseline	-0.66 (0.074)	-0.94 (0.075)	-0.30 (0.076)

2. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Description	Mean change from baseline in FPG at Week 24, adjusted for baseline value.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.

Arm/Group Title	Saxagliptin 2.5 mg Plus Open-label TZD	Saxagliptin 5 mg Plus Open-label TZD	Placebo Plus Open-label TZD
Arm/Group Description	The Saxagliptin 2.5 mg + Open-Label TZD group includes data from subjects randomized to receive coadministration of blinded Saxagliptin 2.5 mg plus open-label pioglitazone 30 mg or 45 mg once daily (QD), or open label rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	The Saxagliptin 5 mg + Open-Label TZD group includes data from subjects randomized to receive coadministration of blinded Saxagliptin 5 mg plus pioglitazone 30 mg or 45 mg once daily (QD), or rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	The placebo + open-label TZD group includes data from subjects randomized to receive coadministration of blinded placebo plus pioglitazone 30 mg or 45 mg once daily (QD), or rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.
Measure Participants	193	185	181
Baseline Mean	163.0 (3.54)	159.5 (3.34)	162.4 (3.43)
Week 24 Mean	148.2 (3.36)	143.0 (3.20)	159.3 (4.29)
Adjusted Mean Change from Baseline	-14.3 (2.87)	-17.3 (2.94)	-2.8 (2.97)

3. Secondary Outcome

Title	Percentage of Participants Achieving A1c <7% at Week 24
Description	Percentage of participants achieving A1C < 7%, the American Diabetic Association's defined goal for glycemia, at each dose of saxagliptin plus TZD versus placebo plus TZD at Week 24.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in the Week 24 LOCF analysis, subjects must have had at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.

Arm/Group Title	Saxagliptin 2.5 mg Plus Open-label TZD	Saxagliptin 5 mg Plus Open-label TZD	Placebo Plus Open-label TZD
Arm/Group Description	The Saxagliptin 2.5 mg + Open-Label TZD group includes data from subjects randomized to receive coadministration of blinded Saxagliptin 2.5 mg plus open-label pioglitazone 30 mg or 45 mg once daily (QD), or open label rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	The Saxagliptin 5 mg + Open-Label TZD group includes data from subjects randomized to receive coadministration of blinded Saxagliptin 5 mg plus pioglitazone 30 mg or 45 mg once daily (QD), or rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	The placebo + open-label TZD group includes data from subjects randomized to receive coadministration of blinded placebo plus pioglitazone 30 mg or 45 mg once daily (QD), or rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.
Measure Participants	192	184	180
Number [Percentage of participants]	42.2 21.6%	41.8 22.5%	25.6 13.9%

4. Secondary Outcome

Title	Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24
Description	Mean change from baseline for 0 to 180 minutes PPG AUC achieved at each dose of saxagliptin plus TZD versus placebo plus TZD at Week 24, adjusted for baseline value.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis of change from baseline to Week 24 LOCF, participants must have had a baseline and at least 1 post-baseline measurement. If a participant received rescue medication, then that measurement must have been taken before rescue.

Arm/Group Title	Saxagliptin 2.5 mg Plus Open-label TZD	Saxagliptin 5 mg Plus Open-label TZD	Placebo Plus Open-label TZD
Arm/Group Description	The Saxagliptin 2.5 mg + Open-Label TZD group includes data from subjects randomized to receive coadministration of blinded Saxagliptin 2.5 mg plus open-label pioglitazone 30 mg or 45 mg once daily (QD), or open label rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	The Saxagliptin 5 mg + Open-Label TZD group includes data from subjects randomized to receive coadministration of blinded Saxagliptin 5 mg plus pioglitazone 30 mg or 45 mg once daily (QD), or rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.	The placebo + open-label TZD group includes data from subjects randomized to receive coadministration of blinded placebo plus pioglitazone 30 mg or 45 mg once daily (QD), or rosiglitazone 4 mg QD, or 8 mg, either QD or in 2 divided doses of 4 mg.
Measure Participants	151	131	123
Baseline Mean	48301 (968.5)	47866 (1048.9)	47256 (1057.4)
Week 24 Mean	40255 (919.7)	38587 (991.3)	44819 (1023.4)
Adjusted Mean Change from Baseline	-7849 (740.6)	-9269 (794.9)	-2690 (820.6)

Adverse Events

Arm/Group Title	PLA + TZD		SAXA 2.5MG + TZD		SAXA 5MG + TZD
Arm/Group Description
All Cause Mortality
	PLA + TZD		SAXA 2.5MG + TZD		SAXA 5MG + TZD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	PLA + TZD		SAXA 2.5MG + TZD		SAXA 5MG + TZD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/184 (10.9%)		19/195 (9.7%)		18/186 (9.7%)
Cardiac disorders
TACHYCARDIA	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
ANGINA PECTORIS	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
ATRIAL FIBRILLATION	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
CORONARY ARTERY DISEASE	3/184 (1.6%)		1/195 (0.5%)		0/186 (0%)
CARDIAC FAILURE CONGESTIVE	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
ACUTE MYOCARDIAL INFARCTION	1/184 (0.5%)		1/195 (0.5%)		0/186 (0%)
Eye disorders
CATARACT	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
Gastrointestinal disorders
VOMITING	1/184 (0.5%)		0/195 (0%)		1/186 (0.5%)
DIARRHOEA	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
GASTRITIS	1/184 (0.5%)		1/195 (0.5%)		0/186 (0%)
ANAL FISTULA	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
ABDOMINAL PAIN	1/184 (0.5%)		1/195 (0.5%)		1/186 (0.5%)
PANCREATITIS ACUTE	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
IRRITABLE BOWEL SYNDROME	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
SMALL INTESTINAL OBSTRUCTION	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
General disorders
PYREXIA	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
CHEST PAIN	1/184 (0.5%)		1/195 (0.5%)		1/186 (0.5%)
SUDDEN DEATH	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
Hepatobiliary disorders
CHOLECYSTITIS	0/184 (0%)		2/195 (1%)		0/186 (0%)
Infections and infestations
ORCHITIS	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
PNEUMONIA	1/184 (0.5%)		0/195 (0%)		1/186 (0.5%)
ANAL ABSCESS	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
APPENDICITIS	1/184 (0.5%)		1/195 (0.5%)		0/186 (0%)
GASTROENTERITIS	0/184 (0%)		2/195 (1%)		1/186 (0.5%)
MENINGITIS ASEPTIC	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
STAPHYLOCOCCAL INFECTION	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
Injury, poisoning and procedural complications
OVERDOSE	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
BACK INJURY	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
LIMB INJURY	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
FIBULA FRACTURE	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
ROAD TRAFFIC ACCIDENT	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
Investigations
BLOOD PRESSURE INCREASED	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
Metabolism and nutrition disorders
DEHYDRATION	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
HYPOVOLAEMIA	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
Musculoskeletal and connective tissue disorders
BACK PAIN	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
OSTEOARTHRITIS	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
INTERVERTEBRAL DISC PROTRUSION	0/184 (0%)		1/195 (0.5%)		1/186 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
COLON NEOPLASM	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
MALIGNANT MELANOMA	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
BASAL CELL CARCINOMA	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
SQUAMOUS CELL CARCINOMA	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
METASTATIC SQUAMOUS CELL CARCINOMA	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
Nervous system disorders
CEREBRAL HAEMATOMA	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
CEREBRAL INFARCTION	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
CEREBELLAR HAEMORRHAGE	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
CAROTID ARTERY STENOSIS	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
CEREBROVASCULAR ACCIDENT	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
TRANSIENT ISCHAEMIC ATTACK	1/184 (0.5%)		1/195 (0.5%)		0/186 (0%)
Psychiatric disorders
ANXIETY	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
ALCOHOL ABUSE	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
Renal and urinary disorders
RENAL CYST	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
NEPHROLITHIASIS	1/184 (0.5%)		0/195 (0%)		1/186 (0.5%)
CALCULUS BLADDER	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
CALCULUS URETERIC	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
Reproductive system and breast disorders
ENDOMETRIOSIS	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
PROSTATOMEGALY	0/184 (0%)		0/195 (0%)		1/186 (0.5%)
POSTMENOPAUSAL HAEMORRHAGE	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
Respiratory, thoracic and mediastinal disorders
ASTHMA	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
Skin and subcutaneous tissue disorders
RASH	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
SKIN ULCER	1/184 (0.5%)		0/195 (0%)		0/186 (0%)
Vascular disorders
HYPERTENSION	0/184 (0%)		1/195 (0.5%)		0/186 (0%)
Other (Not Including Serious) Adverse Events
	PLA + TZD		SAXA 2.5MG + TZD		SAXA 5MG + TZD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	109/184 (59.2%)		107/195 (54.9%)		109/186 (58.6%)
Blood and lymphatic system disorders
ANAEMIA	3/184 (1.6%)		3/195 (1.5%)		11/186 (5.9%)
Gastrointestinal disorders
DIARRHOEA	13/184 (7.1%)		8/195 (4.1%)		10/186 (5.4%)
General disorders
PYREXIA	8/184 (4.3%)		6/195 (3.1%)		11/186 (5.9%)
OEDEMA PERIPHERAL	19/184 (10.3%)		9/195 (4.6%)		26/186 (14%)
Infections and infestations
BRONCHITIS	9/184 (4.9%)		11/195 (5.6%)		7/186 (3.8%)
NASOPHARYNGITIS	15/184 (8.2%)		9/195 (4.6%)		15/186 (8.1%)
URINARY TRACT INFECTION	17/184 (9.2%)		23/195 (11.8%)		20/186 (10.8%)
UPPER RESPIRATORY TRACT INFECTION	19/184 (10.3%)		25/195 (12.8%)		24/186 (12.9%)
Musculoskeletal and connective tissue disorders
BACK PAIN	7/184 (3.8%)		12/195 (6.2%)		12/186 (6.5%)
ARTHRALGIA	13/184 (7.1%)		22/195 (11.3%)		10/186 (5.4%)
MUSCULOSKELETAL PAIN	6/184 (3.3%)		10/195 (5.1%)		12/186 (6.5%)
Nervous system disorders
HEADACHE	12/184 (6.5%)		15/195 (7.7%)		15/186 (8.1%)
DIZZINESS	14/184 (7.6%)		10/195 (5.1%)		7/186 (3.8%)
Respiratory, thoracic and mediastinal disorders
COUGH	13/184 (7.1%)		9/195 (4.6%)		5/186 (2.7%)
Vascular disorders
HYPERTENSION	12/184 (6.5%)		15/195 (7.7%)		11/186 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.