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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00614939
Recruitment Status : Completed
First Posted : February 13, 2008
Results First Posted : July 7, 2010
Last Update Posted : May 19, 2011
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Type 2 Diabetes
Interventions Drug: Saxagliptin
Drug: Placebo
Enrollment 572
Recruitment Details  
Pre-assignment Details 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
Hide Arm/Group Description Placebo Saxagliptin 2.5 mg once daily oral dose
Period Title: Overall Study
Started 85 [1] 85 [1]
Completed 50 [2] 42 [2]
Not Completed 35 43
Reason Not Completed
Withdrawal by Subject             10             17
Study specific discontinuation criteris             13             16
Adverse Event             2             5
Incorrect enrollment             1             2
Death             4             3
Poor/non-compliance             4             0
Hospitalized due to kidney transplant             1             0
[1]
Randomized and treated
[2]
Completed 52 weeks of treatment
Arm/Group Title Placebo Saxa Total
Hide Arm/Group Description Placebo Saxagliptin 2.5 mg once daily oral dose Total of all reporting groups
Overall Number of Baseline Participants 85 85 170
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 85 participants 85 participants 170 participants
66.2  (9.08) 66.8  (8.27) 66.5  (8.66)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 85 participants 85 participants 170 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 85 participants 85 participants 170 participants
Moderate 42 48 90
Severe 23 18 41
End-Stage 20 19 39
Baseline Diabetes Therapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 85 participants 85 participants 170 participants
Diabetes Therapy 84 83 167
Insulin 57 71 128
Oral blood glucose lowering drug 30 23 53
1.Primary Outcome
Title Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 12 Last Observation Carried Forward (LOCF)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 83 81
Mean (Standard Error)
Unit of Measure: Percent
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)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Saxa
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
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 [Not Specified]
2.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF)- Moderate Renal Impairment Subgroup
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 40 44
Mean (Standard Error)
Unit of Measure: mg/dL
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.339
Comments [Not Specified]
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 [Not Specified]
3.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 23 18
Mean (Standard Error)
Unit of Measure: mg/dL
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.798
Comments [Not Specified]
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 [Not Specified]
4.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 18 15
Mean (Standard Error)
Unit of Measure: mg/dL
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments [Not Specified]
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 [Not Specified]
5.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Moderate Renal Impairment Subgroup
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 40 44
Mean (Standard Error)
Unit of Measure: mmol/L
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Footnote
Comments *Adjusted for baseline FPG
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 [Not Specified]
6.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 23 18
Mean (Standard Error)
Unit of Measure: mmol/L
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Footnote
Comments *Adjusted for baseline FPG
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 [Not Specified]
7.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 18 15
Mean (Standard Error)
Unit of Measure: mmol/L
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Footnote
Comments *Adjusted for baseline FPG
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 [Not Specified]
8.Secondary Outcome
Title Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 52
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 82 78
Mean (Standard Error)
Unit of Measure: Percent
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)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Saxa
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Repeated Measures
Comments

Number of subjects with observed values at Week 52 was n=26 for saxagliptin and n=34 for placebo

*Adjusted for baseline HbA1c

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 [Not Specified]
9.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 40 44
Mean (Standard Error)
Unit of Measure: mg/dL
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Repeated Measures
Comments

Number of subjects with observed values at Week 52 was n=17 for saxagliptin and n=16 for placebo

*Adjusted for baseline FPG

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 [Not Specified]
10.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 23 18
Mean (Standard Error)
Unit of Measure: mg/dL
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Repeated Measures
Comments

Number of subjects with observed values at Week 52 was n=5 for saxagliptin and n=11 for placebo.

*Adjusted for baseline FPG

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 [Not Specified]
11.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 18 15
Mean (Standard Error)
Unit of Measure: mg/dL
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Repeated Measures
Comments

Number of subjects with observed values at Week 52 was n=2 for saxagliptin and n=5 for placebo.

*Adjusted for baseline FPG

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 [Not Specified]
12.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 40 44
Mean (Standard Error)
Unit of Measure: mmol/L
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Repeated Measures
Comments

Number of subjects with observed values at Week 52 was n=17 for saxagliptin and n=16 for placebo.

*Adjusted for baseline FPG

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 [Not Specified]
13.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup
Hide 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
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 23 18
Mean (Standard Error)
Unit of Measure: mmol/L
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Repeated Measures
Comments

Number of subjects with observed values at Week 52 was n=5 for saxagliptin and n=11 for placebo.

*Adjusted for baseline FPG

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 [Not Specified]
14.Secondary Outcome
Title Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup
Hide 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
Hide Outcome Measure Data
Hide 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
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Placebo
Saxagliptin 2.5 mg once daily oral dose
Overall Number of Participants Analyzed 18 15
Mean (Standard Error)
Unit of Measure: mmol/L
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Repeated Measures
Comments

Number of subjects with observed values at Week 52 was n=2 for saxagliptin and n=5 for placebo.

*Adjusted for baseline FPG

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 [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Saxa
Hide Arm/Group Description Placebo Saxagliptin 2.5 mg once daily oral dose
All-Cause Mortality
Placebo Saxa
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Placebo Saxa
Affected / at Risk (%) Affected / at Risk (%)
Total   24/85 (28.24%)   23/85 (27.06%) 
Cardiac disorders     
Cardiac Failure Congestive  1  0/85 (0.00%)  1/85 (1.18%) 
Myocardial Infarction  1  1/85 (1.18%)  2/85 (2.35%) 
Acute Myocardial Infarction  1  0/85 (0.00%)  1/85 (1.18%) 
Cardiac Arrest  1  0/85 (0.00%)  1/85 (1.18%) 
Atrial Fibrillation  1  1/85 (1.18%)  0/85 (0.00%) 
Bifascicular Block  1  1/85 (1.18%)  0/85 (0.00%) 
Cardiac Failure  1  2/85 (2.35%)  0/85 (0.00%) 
Eye disorders     
Cataract  1  0/85 (0.00%)  1/85 (1.18%) 
Iridocyclitis  1  0/85 (0.00%)  1/85 (1.18%) 
Pseudoexfoliation Of Lens Capsule  1  0/85 (0.00%)  1/85 (1.18%) 
Gastrointestinal disorders     
Abdominal Pain Upper  1  0/85 (0.00%)  1/85 (1.18%) 
Diarrhoea  1  0/85 (0.00%)  1/85 (1.18%) 
Gastrointestinal Haemorrhage  1  0/85 (0.00%)  1/85 (1.18%) 
Pancreatitis  1  1/85 (1.18%)  0/85 (0.00%) 
Oedema  1  1/85 (1.18%)  0/85 (0.00%) 
General disorders     
Oedema Peripheral  1  0/85 (0.00%)  1/85 (1.18%) 
Sudden Death  1  2/85 (2.35%)  1/85 (1.18%) 
Infections and infestations     
Cystitis  1  0/85 (0.00%)  1/85 (1.18%) 
Urinary Tract Infection  1  0/85 (0.00%)  1/85 (1.18%) 
Pyelonephritis Acute  1  1/85 (1.18%)  1/85 (1.18%) 
Urosepsis  1  1/85 (1.18%)  0/85 (0.00%) 
Pneumonia  1  0/85 (0.00%)  2/85 (2.35%) 
Cellulitis  1  0/85 (0.00%)  1/85 (1.18%) 
Gangrene  1  1/85 (1.18%)  1/85 (1.18%) 
Pyelonephritis  1  0/85 (0.00%)  1/85 (1.18%) 
Infected Skin Ulcer  1  1/85 (1.18%)  0/85 (0.00%) 
Lobar Pneumonia  1  1/85 (1.18%)  0/85 (0.00%) 
Osteomyelitis  1  1/85 (1.18%)  0/85 (0.00%) 
Sepsis  1  1/85 (1.18%)  0/85 (0.00%) 
Injury, poisoning and procedural complications     
Upper Limb Fracture  1  1/85 (1.18%)  0/85 (0.00%) 
Arteriovenous Fistula Thrombosis  1  1/85 (1.18%)  0/85 (0.00%) 
Wound  1  1/85 (1.18%)  0/85 (0.00%) 
Arteriovenous Fistula Operation  1  1/85 (1.18%)  0/85 (0.00%) 
Investigations     
Alanine Aminotransferase Increased  1  0/85 (0.00%)  1/85 (1.18%) 
Aspartate Aminotransferase Increased  1  0/85 (0.00%)  1/85 (1.18%) 
Blood Glucose Increased  1  0/85 (0.00%)  1/85 (1.18%) 
Metabolism and nutrition disorders     
Diabetes Mellitus  1  1/85 (1.18%)  0/85 (0.00%) 
Hypoglycaemia  1  2/85 (2.35%)  0/85 (0.00%) 
Diabetes Mellitus Inadequate Control  1  1/85 (1.18%)  1/85 (1.18%) 
Hyperglycaemia  1  1/85 (1.18%)  0/85 (0.00%) 
Musculoskeletal and connective tissue disorders     
Osteochondrosis  1  1/85 (1.18%)  0/85 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant Fibrous Histiocytoma  1  0/85 (0.00%)  1/85 (1.18%) 
Nervous system disorders     
Cauda Equina Syndrome  1  0/85 (0.00%)  1/85 (1.18%) 
Cerebrovascular Accident  1  1/85 (1.18%)  1/85 (1.18%) 
Dizziness  1  0/85 (0.00%)  1/85 (1.18%) 
Cerebral Hypoperfusion  1  1/85 (1.18%)  0/85 (0.00%) 
Renal and urinary disorders     
Renal Impairment  1  1/85 (1.18%)  1/85 (1.18%) 
Calculus Ureteric  1  0/85 (0.00%)  1/85 (1.18%) 
Renal Failure Chronic  1  1/85 (1.18%)  0/85 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/85 (0.00%)  1/85 (1.18%) 
Interstitial Lung Disease  1  0/85 (0.00%)  1/85 (1.18%) 
Orthopnoea  1  0/85 (0.00%)  1/85 (1.18%) 
Skin and subcutaneous tissue disorders     
Skin Ulcer  1  0/85 (0.00%)  1/85 (1.18%) 
Skin Disorder  1  1/85 (1.18%)  0/85 (0.00%) 
Vascular disorders     
Hypertension  1  0/85 (0.00%)  1/85 (1.18%) 
Poor Peripheral Circulation  1  0/85 (0.00%)  1/85 (1.18%) 
Hypertensive crisis  1  1/85 (1.18%)  0/85 (0.00%) 
Peripheral Arterial Occlusive Disease  1  1/85 (1.18%)  0/85 (0.00%) 
Arteriovenous Fistula  1  0/85 (0.00%)  1/85 (1.18%) 
Orthostatic Hypotension  1  0/85 (0.00%)  1/85 (1.18%) 
Arteriosclerosis  1  1/85 (1.18%)  0/85 (0.00%) 
Femoral Artery Occlusion  1  1/85 (1.18%)  0/85 (0.00%) 
Peripheral Ischaemia  1  1/85 (1.18%)  0/85 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Saxa
Affected / at Risk (%) Affected / at Risk (%)
Total   36/85 (42.35%)   38/85 (44.71%) 
Blood and lymphatic system disorders     
Anaemia   7/85 (8.24%)  5/85 (5.88%) 
General disorders     
Oedema Peripheral   6/85 (7.06%)  2/85 (2.35%) 
Infections and infestations     
Urinary Tract Infection   3/85 (3.53%)  5/85 (5.88%) 
Metabolism and nutrition disorders     
Hypoglycaemia  1  25/85 (29.41%)  24/85 (28.24%) 
Vascular disorders     
Hypertension   5/85 (5.88%)  5/85 (5.88%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
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.
Results Point of Contact
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Name/Title: Gerard Lynch
Organization: AstraZeneca
EMail: aztrial_results_posting@astrazeneca.com
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Responsible Party: Peter Ohman, MD, PhD, Medical Science Director, AstraZeneca
ClinicalTrials.gov Identifier: NCT00614939    
Other Study ID Numbers: D1680C00007
EudraCT number 2007-004951-12
First Submitted: January 31, 2008
First Posted: February 13, 2008
Results First Submitted: June 7, 2010
Results First Posted: July 7, 2010
Last Update Posted: May 19, 2011