Treatment Effect of Saxagliptin Compared With Placebo in Patients With Type 2 Diabetes and Renal Impairment

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00614939
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 572
• Locations: 75
• Arms: 2
• Duration (Months): 26
• Patients Per Site: 7.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Saxagliptin is a new investigational medication being developed for treatment of type 2 diabetes. This study is designed to test the efficacy of once daily saxagliptin in renally impaired patients.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Saxagliptin; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 572 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Short-term 12-Week, Multi-centre, Randomized, Parallel-group, Double-blind, Placebo-controlled Study to Evaluate the Treatment Effect of Saxagliptin Compared With Placebo in Adult Patients With Type 2 Diabetes and Renal Impairment (Moderate, Severe, and End-Stage) With an Additional 40-week, Randomized, Double-blind, Placebo-controlled Long-term Observational Period.
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Saxa Saxagliptin	Drug: Saxagliptin; 2.5 mg once daily oral dose; Other Names: Onglyza
No Intervention: Placebo Placebo to match	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 12 Last Observation Carried Forward (LOCF) [Baseline , Week 12 (LOCF)]

   Adjusted* mean change from baseline in HbA1c achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.

Secondary Outcome Measures

1. Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF)- Moderate Renal Impairment Subgroup [Baseline, Week 12 (LOCF)]

   Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the moderate renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.

2. Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup [Baseline, Week 12 (LOCF)]

   Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the severe renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.

3. Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup [Baseline, Week 12 (LOCF)]

   Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the end-stage renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.

4. Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Moderate Renal Impairment Subgroup [Baseline, Week 12 (LOCF)]

   Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the moderate renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.

5. Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 52 [Baseline , Week 52]

   Adjusted* mean change from baseline in HbA1c achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.

6. Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup [Baseline, Week 52]

   Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the moderate renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.

7. Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup [Baseline, Week 52]

   Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the severe renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.

8. Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup [Baseline, Week 52]

   Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the end-stage renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.

9. Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup [Baseline, Week 52]

   Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the moderate renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with type 2 diabetes

• Documented history of CrCl <50 ml/min within the 3 months prior to enrollment

• HbA1c ≥7.0% and ≤11.0%

Exclusion Criteria:

• Type 1 diabetes, history of diabetic ketoacidosis or hyposmolar non-ketonic coma

• Previous or current treatment with any DPP-IV inhibitor and/or GLP-1 mimetic.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Concord	California	United States
2	Research Site	Sacramento	California	United States
3	Research Site	Denver	Colorado	United States
4	Research Site	Topeka	Kansas	United States
5	Research Site	Baltimore	Maryland	United States
6	Research Site	Great Falls	Montana	United States
7	Research Site	Greenville	North Carolina	United States
8	Research Site	Morehead City	North Carolina	United States
9	Research Site	Cincinnati	Ohio	United States
10	Research Site	Corpus Christi	Texas	United States
11	Research Site	Charleston	West Virginia	United States
12	Research Site	Brest		Belarus
13	Research Site	Gomel		Belarus
14	Research Site	Minsk		Belarus
15	Research Site	Dimitrovgrad		Bulgaria
16	Research Site	Sofia		Bulgaria
17	Research Site	Veliko Tarnovo		Bulgaria
18	Research Site	Karlovac		Croatia
19	Research Site	Osijek		Croatia
20	Research Site	Rijeka		Croatia
21	Research Site	Split		Croatia
22	Research Site	Zagreb		Croatia
23	Research Site	Moravsky Krumlov		Czech Republic
24	Research Site	Praha 10		Czech Republic
25	Research Site	Teplice		Czech Republic
26	Research Site	Usti Nad Labem		Czech Republic
27	Research Site	Znojmo		Czech Republic
28	Research Site	Tallinn		Estonia
29	Research Site	Dieburg		Germany
30	Research Site	Dusseldorf		Germany
31	Research Site	Hannover		Germany
32	Research Site	Heidelberg		Germany
33	Research Site	Mannheim		Germany
34	Research Site	Debrecen		Hungary
35	Research Site	Gyor		Hungary
36	Research Site	Kalocsa		Hungary
37	Research Site	Kecskemet		Hungary
38	Research Site	Zalaegerszeg		Hungary
39	Research Site	Riga		Latvia
40	Research Site	Kaunas		Lithuania
41	Research Site	Klaipeda		Lithuania
42	Research Site	Panevezys		Lithuania
43	Research Site	Vilnius		Lithuania
44	Research Site	Lodz	90-153	Poland
45	Research Site	Bialystok		Poland
46	Research Site	Ciechanow		Poland
47	Research Site	Golub Dobrzyn		Poland
48	Research Site	Grodzisk Mazowiecki		Poland
49	Research Site	Katowice		Poland
50	Research Site	Krakow		Poland
51	Research Site	Makow Mazowiecki		Poland
52	Research Site	Radom		Poland
53	Research Site	Szczecin		Poland
54	Research Site	Warszawa		Poland
55	Research Site	Wroclaw		Poland
56	Research Site	Zabrze		Poland
57	Research Site	Satu-mare	Satu Mare	Romania
58	Research Site	Bacau		Romania
59	Research Site	Brasov		Romania
60	Research Site	Bucharest		Romania
61	Research Site	Bucuresti		Romania
62	Research Site	Sf Gheorghe		Romania
63	Research Site	Chelyabinsk		Russian Federation
64	Research Site	Moscow		Russian Federation
65	Research Site	Ryazan		Russian Federation
66	Research Site	St.petersburg		Russian Federation
67	Research Site	Yaroslavl		Russian Federation
68	Research Site	Dnipropetrovsk		Ukraine
69	Research Site	Ivano-frankivsk		Ukraine
70	Research Site	Kharkiv		Ukraine
71	Research Site	Kyiv		Ukraine
72	Research Site	Mykolayiv		Ukraine
73	Research Site	Sumy		Ukraine
74	Research Site	Ternopil		Ukraine
75	Research Site	Zaporizhzhya		Ukraine

Sponsors and Collaborators

• AstraZeneca
• Bristol-Myers Squibb

Investigators

• Study Director: Peter Ohman, MD, PhD, AstraZeneca
• Study Chair: Deborah Price, MSc, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00614939
• Other Study ID Numbers: D1680C00007; EudraCT number 2007-004951-12
• First Posted: Feb 13, 2008
• Last Update Posted: May 19, 2011
• Last Verified: May 1, 2011

• Keywords provided by , ,: DPP-4 inhibitors; HbA1c; incretins; Renal Impairment
• Additional relevant MeSH terms: Renal Insufficiency; Diabetes Mellitus; Diabetes Mellitus, Type 2; Saxagliptin

Study Results

Participant Flow

Pre-assignment Detail	A total of 572 participants were enrolled in the study; 561 entered the Lead-in period and 170 patients were randomized and treated.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Period Title: Overall Study
STARTED	85	85
COMPLETED	50	42
NOT COMPLETED	35	43

Baseline Characteristics

Arm/Group Title	Placebo	Saxa	Total
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose	Total of all reporting groups
Overall Participants	85	85	170
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.2 (9.08)	66.8 (8.27)	66.5 (8.66)
Sex: Female, Male (Count of Participants)
Female	44 51.8%	53 62.4%	97 57.1%
Male	41 48.2%	32 37.6%	73 42.9%
Baseline Renal Impairment Category (Number) [Number]
Moderate	42 49.4%	48 56.5%	90 52.9%
Severe	23 27.1%	18 21.2%	41 24.1%
End-Stage	20 23.5%	19 22.4%	39 22.9%
Baseline Diabetes Therapy (participants) [Number]
Diabetes Therapy	84 98.8%	83 97.6%	167 98.2%
Insulin	57 67.1%	71 83.5%	128 75.3%
Oral blood glucose lowering drug	30 35.3%	23 27.1%	53 31.2%

Outcome Measures

1. Primary Outcome

Title	Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 12 Last Observation Carried Forward (LOCF)
Description	Adjusted* mean change from baseline in HbA1c achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.
Time Frame	Baseline , Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 12 (LOCF) for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	83	81
Baseline	8.09 (0.119)	8.45 (0.135)
Week 12	7.80 (0.137)	7.63 (0.132)
Adjusted Mean Change from Baseline	-0.44 (0.109)	-0.86 (0.112)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	ANCOVA
	Comments	*Adjusted for baseline HbA1c
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -0.71 to -0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.151
	Estimation Comments

2. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF)- Moderate Renal Impairment Subgroup
Description	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the moderate renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.
Time Frame	Baseline, Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 12 (LOCF) for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	40	44
Baseline	162.33 (8.933)	202.82 (9.858)
Week 12	174.50 (10.089)	173.91 (7.938)
Adjusted Mean Change from Baseline	-2.88 (9.073)	-15.22 (8.630)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments	Additional details about the analysis, such as null hypothesis and power calculation: Due to a statistically significant treatment-by-baseline renal impairment interaction, fasting plasma glucose results were analyzed separately for each baseline renal impairment category.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.339
	Comments
	Method	ANCOVA
	Comments	*Adjusted for baseline FPG
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-12.34
	Confidence Interval	() 95%; -37.91 to 13.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 12.847
	Estimation Comments

3. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup
Description	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the severe renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.
Time Frame	Baseline, Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 12 (LOCF) for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	23	18
Baseline	173.48 (11.630)	165.50 (19.909)
Week 12	141.52 (14.276)	133.83 (11.371)
Adjusted mean change	-29.91 (11.212)	-34.28 (12.677)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments	Additional details about the analysis, such as null hypothesis and power calculation: Due to a statistically significant treatment-by-baseline renal impairment interaction, fasting plasma glucose results were analyzed separately for each baseline renal impairment category.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.798
	Comments
	Method	ANCOVA
	Comments	*Adjusted for baseline FPG
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.36
	Confidence Interval	(2-Sided) 95%; -38.65 to 29.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 16.938
	Estimation Comments

4. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup
Description	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the end-stage renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.
Time Frame	Baseline, Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 12 (LOCF) for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	18	15
Baseline	170.39 (14.518)	177.07 (10.638)
Week 12	161.11 (12.624)	207.60 (30.515)
Adjusted mean change	-11.18 (20.752)	32.82 (22.737)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments	Additional details about the analysis, such as null hypothesis and power calculation: Due to a statistically significant treatment-by-baseline renal impairment interaction, fasting plasma glucose results were analyzed separately for each baseline renal impairment category.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.164
	Comments
	Method	ANCOVA
	Comments	*Adjusted for baseline FPG
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	44.01
	Confidence Interval	(2-Sided) 95%; -18.93 to 106.94
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 30.815
	Estimation Comments

5. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Moderate Renal Impairment Subgroup
Description	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the moderate renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.
Time Frame	Baseline, Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 12 (LOCF) for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	40	44
Baseline	9.01 (0.495)	11.25 (0.548)
Week 12	9.68 (0.560)	9.65 (0.441)
Absolute mean change	-0.16 (0.504)	-0.84 (0.479)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments	Additional details about the analysis, such as null hypothesis and power calculation: Due to a statistically significant treatment-by-baseline renal impairment interaction, fasting plasma glucose results were analyzed separately for each baseline renal impairment category.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.68
	Confidence Interval	(2-Sided) 95%; -2.10 to 0.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.713
	Estimation Comments

6. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup
Description	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the severe renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.
Time Frame	Baseline, Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 12 (LOCF) for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	23	18
Baseline	9.63 (0.646)	9.17 (1.105)
Week 12	7.86 (0.793)	7.43 (0.632)
Adjusted mean change	-1.66 (0.623)	-1.89 (0.704)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments	Additional details about the analysis, such as null hypothesis and power calculation: Due to a statistically significant treatment-by-baseline renal impairment interaction, fasting plasma glucose results were analyzed separately for each baseline renal impairment category.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -2.14 to 1.67
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.941
	Estimation Comments

7. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup
Description	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 12 (Full Analysis Set) for the end-stage renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 12 value minus the baseline value.
Time Frame	Baseline, Week 12 (LOCF)

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 12 (LOCF) for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	18	15
Baseline	9.46 (0.807)	9.83 (0.591)
Week 12	8.94 (0.700)	11.52 (1.692)
Adjusted mean change	-0.62 (1.151)	1.81 (1.261)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments	Additional details about the analysis, such as null hypothesis and power calculation: Due to a statistically significant treatment-by-baseline renal impairment interaction, fasting plasma glucose results were analyzed separately for each baseline renal impairment category.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.44
	Confidence Interval	(2-Sided) 95%; -1.05 to 5.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.709
	Estimation Comments

8. Secondary Outcome

Title	Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 52
Description	Adjusted* mean change from baseline in HbA1c achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.
Time Frame	Baseline , Week 52

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 52 for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement. Data were excluded after changes in oral blood glucose lowering drug or insulin.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	82	78
Baseline	8.10 (0.120)	8.44 (0.134)
Week 52	7.93 (0.173)	7.41 (0.138)
Adjusted mean change	-0.53 (0.154)	-1.35 (0.174)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.82
	Confidence Interval	(2-Sided) 95%; -1.27 to -0.37
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.228
	Estimation Comments

9. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup
Description	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the moderate renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 52 for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement. Data were excluded after changes in oral blood glucose lowering drug or insulin.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	40	44
Baseline	162.33 (8.933)	202.82 (9.858)
Week 52	174.83 (11.295)	177.43 (7.637)
Adjusted mean change	3.02 (13.277)	-14.96 (12.873)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments	Additional details about the analysis, such as null hypothesis and power calculation: Due to a statistically significant treatment-by-baseline renal impairment interaction, fasting plasma glucose results were analyzed separately for each baseline renal impairment category.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-17.98
	Confidence Interval	(2-Sided) 95%; -54.28 to 18.33
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 18.475
	Estimation Comments

10. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup
Description	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the severe renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 52 for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement. Data were excluded after changes in oral blood glucose lowering drug or insulin.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	23	18
Baseline	173.48 (11.630)	165.50 (19.909)
Week 52	151.78 (9.896)	139.06 (12.408)
Adjusted mean change	-24.59 (14.510)	-40.32 (20.789)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments	Additional details about the analysis, such as null hypothesis and power calculation: Due to a statistically significant treatment-by-baseline renal impairment interaction, fasting plasma glucose results were analyzed separately for each baseline renal impairment category.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-15.73
	Confidence Interval	(2-Sided) 95%; -65.77 to 34.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 25.326
	Estimation Comments

11. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup
Description	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the end-stage renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 52 for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement. Data were excluded after changes in oral blood glucose lowering drug or insulin.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	18	15
Baseline	170.39 (14.518)	177.07 (10.638)
Week 52	161.94 (13.097)	214.27 (31.740)
Adjusted mean change	-2.18 (29.226)	-40.28 (45.470)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments	Additional details about the analysis, such as null hypothesis and power calculation: Due to a statistically significant treatment-by-baseline renal impairment interaction, fasting plasma glucose results were analyzed separately for each baseline renal impairment category.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-38.09
	Confidence Interval	(2-Sided) 95%; -144.44 to 68.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 53.822
	Estimation Comments

12. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup
Description	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the moderate renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 52 for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement. Data were excluded after changes in oral blood glucose lowering drug or insulin.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	40	44
Baseline	9.01 (0.495)	11.25 (0.548)
Week 52	9.70 (0.627)	9.85 (0.424)
Adjusted mean change	0.15 (0.738)	-0.82 (0.715)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments	Additional details about the analysis, such as null hypothesis and power calculation: Due to a statistically significant treatment-by-baseline renal impairment interaction, fasting plasma glucose results were analyzed separately for each baseline renal impairment category.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.97
	Confidence Interval	(2-Sided) 95%; -2.99 to 1.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.027
	Estimation Comments

13. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup
Description	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the severe renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 52 for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement. Data were excluded after changes in oral blood glucose lowering drug or insulin.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	23	18
Baseline	9.63 (0.646)	9.17 (1.105)
Week 52	8.42 (0.551)	7.71 (0.688)
Adjusted mean change	-1.37 (0.805)	-2.25 (1.154)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments	Additional details about the analysis, such as null hypothesis and power calculation: Due to a statistically significant treatment-by-baseline renal impairment interaction, fasting plasma glucose results were analyzed separately for each baseline renal impairment category.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -3.66 to 1.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.405
	Estimation Comments

14. Secondary Outcome

Title	Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup
Description	Adjusted* mean change from baseline in fasting plasma glucose (FPG) achieved with saxagliptin 2.5 mg once daily versus placebo at Week 52 (Full Analysis Set) for the end-stage renal impairment subgroup. FPG is a continuous measure, the change from baseline for each participant is calculated at the Week 52 value minus the baseline value.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Randomized participants who took at least 1 dose of double-blind treatment. To be included in analysis: change from baseline to Week 52 for efficacy, subjects must have had a baseline and at least 1 post-baseline efficacy measurement. Data were excluded after changes in oral blood glucose lowering drug or insulin.

Arm/Group Title	Placebo	Saxa
Arm/Group Description	Placebo	Saxagliptin 2.5 mg once daily oral dose
Measure Participants	18	15
Baseline	9.46 (0.807)	9.83 (0.591)
Week 52	8.99 (0.728)	11.89 (1.760)
Adjusted mean change	-0.11 (1.621)	-2.25 (2.522)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Saxa
	Comments	Additional details about the analysis, such as null hypothesis and power calculation: Due to a statistically significant treatment-by-baseline renal impairment interaction, fasting plasma glucose results were analyzed separately for each baseline renal impairment category.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.14
	Confidence Interval	(2-Sided) 95%; -8.04 to 3.76
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.985
	Estimation Comments

Adverse Events

Arm/Group Title	Placebo		Saxa
Arm/Group Description	Placebo		Saxagliptin 2.5 mg once daily oral dose
All Cause Mortality
	Placebo		Saxa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Saxa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/85 (28.2%)		23/85 (27.1%)
Cardiac disorders
Cardiac Failure Congestive	0/85 (0%)		1/85 (1.2%)
Myocardial Infarction	1/85 (1.2%)		2/85 (2.4%)
Acute Myocardial Infarction	0/85 (0%)		1/85 (1.2%)
Cardiac Arrest	0/85 (0%)		1/85 (1.2%)
Atrial Fibrillation	1/85 (1.2%)		0/85 (0%)
Bifascicular Block	1/85 (1.2%)		0/85 (0%)
Cardiac Failure	2/85 (2.4%)		0/85 (0%)
Eye disorders
Cataract	0/85 (0%)		1/85 (1.2%)
Iridocyclitis	0/85 (0%)		1/85 (1.2%)
Pseudoexfoliation Of Lens Capsule	0/85 (0%)		1/85 (1.2%)
Gastrointestinal disorders
Abdominal Pain Upper	0/85 (0%)		1/85 (1.2%)
Diarrhoea	0/85 (0%)		1/85 (1.2%)
Gastrointestinal Haemorrhage	0/85 (0%)		1/85 (1.2%)
Pancreatitis	1/85 (1.2%)		0/85 (0%)
Oedema	1/85 (1.2%)		0/85 (0%)
General disorders
Oedema Peripheral	0/85 (0%)		1/85 (1.2%)
Sudden Death	2/85 (2.4%)		1/85 (1.2%)
Infections and infestations
Cystitis	0/85 (0%)		1/85 (1.2%)
Urinary Tract Infection	0/85 (0%)		1/85 (1.2%)
Pyelonephritis Acute	1/85 (1.2%)		1/85 (1.2%)
Urosepsis	1/85 (1.2%)		0/85 (0%)
Pneumonia	0/85 (0%)		2/85 (2.4%)
Cellulitis	0/85 (0%)		1/85 (1.2%)
Gangrene	1/85 (1.2%)		1/85 (1.2%)
Pyelonephritis	0/85 (0%)		1/85 (1.2%)
Infected Skin Ulcer	1/85 (1.2%)		0/85 (0%)
Lobar Pneumonia	1/85 (1.2%)		0/85 (0%)
Osteomyelitis	1/85 (1.2%)		0/85 (0%)
Sepsis	1/85 (1.2%)		0/85 (0%)
Injury, poisoning and procedural complications
Upper Limb Fracture	1/85 (1.2%)		0/85 (0%)
Arteriovenous Fistula Thrombosis	1/85 (1.2%)		0/85 (0%)
Wound	1/85 (1.2%)		0/85 (0%)
Arteriovenous Fistula Operation	1/85 (1.2%)		0/85 (0%)
Investigations
Alanine Aminotransferase Increased	0/85 (0%)		1/85 (1.2%)
Aspartate Aminotransferase Increased	0/85 (0%)		1/85 (1.2%)
Blood Glucose Increased	0/85 (0%)		1/85 (1.2%)
Metabolism and nutrition disorders
Diabetes Mellitus	1/85 (1.2%)		0/85 (0%)
Hypoglycaemia	2/85 (2.4%)		0/85 (0%)
Diabetes Mellitus Inadequate Control	1/85 (1.2%)		1/85 (1.2%)
Hyperglycaemia	1/85 (1.2%)		0/85 (0%)
Musculoskeletal and connective tissue disorders
Osteochondrosis	1/85 (1.2%)		0/85 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Fibrous Histiocytoma	0/85 (0%)		1/85 (1.2%)
Nervous system disorders
Cauda Equina Syndrome	0/85 (0%)		1/85 (1.2%)
Cerebrovascular Accident	1/85 (1.2%)		1/85 (1.2%)
Dizziness	0/85 (0%)		1/85 (1.2%)
Cerebral Hypoperfusion	1/85 (1.2%)		0/85 (0%)
Renal and urinary disorders
Renal Impairment	1/85 (1.2%)		1/85 (1.2%)
Calculus Ureteric	0/85 (0%)		1/85 (1.2%)
Renal Failure Chronic	1/85 (1.2%)		0/85 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/85 (0%)		1/85 (1.2%)
Interstitial Lung Disease	0/85 (0%)		1/85 (1.2%)
Orthopnoea	0/85 (0%)		1/85 (1.2%)
Skin and subcutaneous tissue disorders
Skin Ulcer	0/85 (0%)		1/85 (1.2%)
Skin Disorder	1/85 (1.2%)		0/85 (0%)
Vascular disorders
Hypertension	0/85 (0%)		1/85 (1.2%)
Poor Peripheral Circulation	0/85 (0%)		1/85 (1.2%)
Hypertensive crisis	1/85 (1.2%)		0/85 (0%)
Peripheral Arterial Occlusive Disease	1/85 (1.2%)		0/85 (0%)
Arteriovenous Fistula	0/85 (0%)		1/85 (1.2%)
Orthostatic Hypotension	0/85 (0%)		1/85 (1.2%)
Arteriosclerosis	1/85 (1.2%)		0/85 (0%)
Femoral Artery Occlusion	1/85 (1.2%)		0/85 (0%)
Peripheral Ischaemia	1/85 (1.2%)		0/85 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Saxa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/85 (42.4%)		38/85 (44.7%)
Blood and lymphatic system disorders
Anaemia	7/85 (8.2%)		5/85 (5.9%)
General disorders
Oedema Peripheral	6/85 (7.1%)		2/85 (2.4%)
Infections and infestations
Urinary Tract Infection	3/85 (3.5%)		5/85 (5.9%)
Metabolism and nutrition disorders
Hypoglycaemia	25/85 (29.4%)		24/85 (28.2%)
Vascular disorders
Hypertension	5/85 (5.9%)		5/85 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.