Type 2 Diabetes
Conditions
Keywords
DPP-4 inhibitors, HbA1c, incretins, Renal Impairment
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.
Interventions
DRUGSaxagliptin
2.5 mg once daily oral dose
DRUGPlacebo
Placebo
Sponsors
Bristol-Myers Squibb
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Belarus, Bulgaria, Croatia, Czechia, Estonia, Germany, Hungary, Latvia, Lithuania, Poland, Romania, Russia, Ukraine, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo | 85 |
| Saxa Saxagliptin 2.5 mg once daily oral dose | 85 |
| Total | 170 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 5 |
| Overall Study | Death | 4 | 3 |
| Overall Study | Hospitalized due to kidney transplant | 1 | 0 |
| Overall Study | Incorrect enrollment | 1 | 2 |
| Overall Study | Poor/non-compliance | 4 | 0 |
| Overall Study | Study specific discontinuation criteris | 13 | 16 |
| Overall Study | Withdrawal by Subject | 10 | 17 |
Baseline characteristics
| Characteristic | Placebo | Saxa | Total |
|---|---|---|---|
| Age Continuous | 66.2 years STANDARD_DEVIATION 9.08 | 66.8 years STANDARD_DEVIATION 8.27 | 66.5 years STANDARD_DEVIATION 8.66 |
| Baseline Diabetes Therapy Diabetes Therapy | 84 participants | 83 participants | 167 participants |
| Baseline Diabetes Therapy Insulin | 57 participants | 71 participants | 128 participants |
| Baseline Diabetes Therapy Oral blood glucose lowering drug | 30 participants | 23 participants | 53 participants |
| Baseline Renal Impairment Category End-Stage | 20 Participants | 19 Participants | 39 Participants |
| Baseline Renal Impairment Category Moderate | 42 Participants | 48 Participants | 90 Participants |
| Baseline Renal Impairment Category Severe | 23 Participants | 18 Participants | 41 Participants |
| Sex: Female, Male Female | 44 Participants | 53 Participants | 97 Participants |
| Sex: Female, Male Male | 41 Participants | 32 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 85 | 38 / 85 |
| serious Total, serious adverse events | 24 / 85 | 23 / 85 |
Outcome results
Primary
Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 12 Last Observation Carried Forward (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.
Time frame: Baseline , Week 12 (LOCF)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 12 Last Observation Carried Forward (LOCF) | Baseline | 8.09 Percent | Standard Error 0.119 |
| Placebo | Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 12 Last Observation Carried Forward (LOCF) | Week 12 | 7.80 Percent | Standard Error 0.137 |
| Placebo | Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 12 Last Observation Carried Forward (LOCF) | Adjusted Mean Change from Baseline | -0.44 Percent | Standard Error 0.109 |
| Saxa | Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 12 Last Observation Carried Forward (LOCF) | Baseline | 8.45 Percent | Standard Error 0.135 |
| Saxa | Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 12 Last Observation Carried Forward (LOCF) | Week 12 | 7.63 Percent | Standard Error 0.132 |
| Saxa | Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 12 Last Observation Carried Forward (LOCF) | Adjusted Mean Change from Baseline | -0.86 Percent | Standard Error 0.112 |
p-value: 0.00795% CI: [-0.71, -0.12]ANCOVA
Secondary
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup | Baseline | 170.39 mg/dL | Standard Error 14.518 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup | Week 12 | 161.11 mg/dL | Standard Error 12.624 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup | Adjusted mean change | -11.18 mg/dL | Standard Error 20.752 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup | Baseline | 177.07 mg/dL | Standard Error 10.638 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup | Week 12 | 207.60 mg/dL | Standard Error 30.515 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup | Adjusted mean change | 32.82 mg/dL | Standard Error 22.737 |
Comparison: 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.p-value: 0.16495% CI: [-18.93, 106.94]ANCOVA
Secondary
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup | Baseline | 9.46 mmol/L | Standard Error 0.807 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup | Week 12 | 8.94 mmol/L | Standard Error 0.7 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup | Adjusted mean change | -0.62 mmol/L | Standard Error 1.151 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup | Baseline | 9.83 mmol/L | Standard Error 0.591 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup | Week 12 | 11.52 mmol/L | Standard Error 1.692 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - End-Stage Renal Impairment Subgroup | Adjusted mean change | 1.81 mmol/L | Standard Error 1.261 |
Comparison: 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.95% CI: [-1.05, 5.93]Footnote
Secondary
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Moderate Renal Impairment Subgroup
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Moderate Renal Impairment Subgroup | Baseline | 9.01 mmol/L | Standard Error 0.495 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Moderate Renal Impairment Subgroup | Week 12 | 9.68 mmol/L | Standard Error 0.56 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Moderate Renal Impairment Subgroup | Absolute mean change | -0.16 mmol/L | Standard Error 0.504 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Moderate Renal Impairment Subgroup | Baseline | 11.25 mmol/L | Standard Error 0.548 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Moderate Renal Impairment Subgroup | Week 12 | 9.65 mmol/L | Standard Error 0.441 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Moderate Renal Impairment Subgroup | Absolute mean change | -0.84 mmol/L | Standard Error 0.479 |
Comparison: 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.95% CI: [-2.1, 0.74]Footnote
Secondary
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF)- Moderate Renal Impairment Subgroup
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF)- Moderate Renal Impairment Subgroup | Baseline | 162.33 mg/dL | Standard Error 8.933 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF)- Moderate Renal Impairment Subgroup | Week 12 | 174.50 mg/dL | Standard Error 10.089 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF)- Moderate Renal Impairment Subgroup | Adjusted Mean Change from Baseline | -2.88 mg/dL | Standard Error 9.073 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF)- Moderate Renal Impairment Subgroup | Baseline | 202.82 mg/dL | Standard Error 9.858 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF)- Moderate Renal Impairment Subgroup | Week 12 | 173.91 mg/dL | Standard Error 7.938 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF)- Moderate Renal Impairment Subgroup | Adjusted Mean Change from Baseline | -15.22 mg/dL | Standard Error 8.63 |
Comparison: 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.p-value: 0.33995% CI: [-37.91, 13.22]ANCOVA
Secondary
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup | Baseline | 9.63 mmol/L | Standard Error 0.646 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup | Week 12 | 7.86 mmol/L | Standard Error 0.793 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup | Adjusted mean change | -1.66 mmol/L | Standard Error 0.623 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup | Baseline | 9.17 mmol/L | Standard Error 1.105 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup | Week 12 | 7.43 mmol/L | Standard Error 0.632 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup | Adjusted mean change | -1.89 mmol/L | Standard Error 0.704 |
Comparison: 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.95% CI: [-2.14, 1.67]Footnote
Secondary
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup | Baseline | 173.48 mg/dL | Standard Error 11.63 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup | Week 12 | 141.52 mg/dL | Standard Error 14.276 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup | Adjusted mean change | -29.91 mg/dL | Standard Error 11.212 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup | Baseline | 165.50 mg/dL | Standard Error 19.909 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup | Week 12 | 133.83 mg/dL | Standard Error 11.371 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 (LOCF) - Severe Renal Impairment Subgroup | Adjusted mean change | -34.28 mg/dL | Standard Error 12.677 |
Comparison: 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.p-value: 0.79895% CI: [-38.65, 29.93]ANCOVA
Secondary
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup | Baseline | 9.46 mmol/L | Standard Error 0.807 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup | Week 52 | 8.99 mmol/L | Standard Error 0.728 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup | Adjusted mean change | -0.11 mmol/L | Standard Error 1.621 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup | Baseline | 9.83 mmol/L | Standard Error 0.591 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup | Week 52 | 11.89 mmol/L | Standard Error 1.76 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup | Adjusted mean change | -2.25 mmol/L | Standard Error 2.522 |
Comparison: 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.95% CI: [-8.04, 3.76]Repeated Measures
Secondary
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup | Baseline | 170.39 mg/dL | Standard Error 14.518 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup | Week 52 | 161.94 mg/dL | Standard Error 13.097 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup | Adjusted mean change | -2.18 mg/dL | Standard Error 29.226 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup | Baseline | 177.07 mg/dL | Standard Error 10.638 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup | Week 52 | 214.27 mg/dL | Standard Error 31.74 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - End-Stage Renal Impairment Subgroup | Adjusted mean change | -40.28 mg/dL | Standard Error 45.47 |
Comparison: 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.95% CI: [-144.44, 68.26]Repeated Measures
Secondary
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup | Baseline | 9.01 mmol/L | Standard Error 0.495 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup | Week 52 | 9.70 mmol/L | Standard Error 0.627 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup | Adjusted mean change | 0.15 mmol/L | Standard Error 0.738 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup | Baseline | 11.25 mmol/L | Standard Error 0.548 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup | Week 52 | 9.85 mmol/L | Standard Error 0.424 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup | Adjusted mean change | -0.82 mmol/L | Standard Error 0.715 |
Comparison: 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.95% CI: [-2.99, 1.04]Repeated Measures
Secondary
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup | Baseline | 162.33 mg/dL | Standard Error 8.933 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup | Week 52 | 174.83 mg/dL | Standard Error 11.295 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup | Adjusted mean change | 3.02 mg/dL | Standard Error 13.277 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup | Baseline | 202.82 mg/dL | Standard Error 9.858 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup | Week 52 | 177.43 mg/dL | Standard Error 7.637 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Moderate Renal Impairment Subgroup | Adjusted mean change | -14.96 mg/dL | Standard Error 12.873 |
Comparison: 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.95% CI: [-54.28, 18.33]Repeated Measures
Secondary
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup | Baseline | 173.48 mg/dL | Standard Error 11.63 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup | Week 52 | 151.78 mg/dL | Standard Error 9.896 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup | Adjusted mean change | -24.59 mg/dL | Standard Error 14.51 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup | Baseline | 165.50 mg/dL | Standard Error 19.909 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup | Week 52 | 139.06 mg/dL | Standard Error 12.408 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup | Adjusted mean change | -40.32 mg/dL | Standard Error 20.789 |
Comparison: 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.95% CI: [-65.77, 34.3]Repeated Measures
Secondary
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup | Baseline | 9.63 mmol/L | Standard Error 0.646 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup | Week 52 | 8.42 mmol/L | Standard Error 0.551 |
| Placebo | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup | Adjusted mean change | -1.37 mmol/L | Standard Error 0.805 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup | Baseline | 9.17 mmol/L | Standard Error 1.105 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup | Week 52 | 7.71 mmol/L | Standard Error 0.688 |
| Saxa | Absolute Change From Baseline in Fasting Plasma Glucose (FPG) to Week 52 - Severe Renal Impairment Subgroup | Adjusted mean change | -2.25 mmol/L | Standard Error 1.154 |
Comparison: 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.95% CI: [-3.66, 1.89]Repeated Measures
Secondary
Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to 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.
Time frame: Baseline , Week 52
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 52 | Baseline | 8.10 Percent | Standard Error 0.12 |
| Placebo | Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 52 | Week 52 | 7.93 Percent | Standard Error 0.173 |
| Placebo | Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 52 | Adjusted mean change | -0.53 Percent | Standard Error 0.154 |
| Saxa | Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 52 | Baseline | 8.44 Percent | Standard Error 0.134 |
| Saxa | Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 52 | Week 52 | 7.41 Percent | Standard Error 0.138 |
| Saxa | Absolute Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) Level to Week 52 | Adjusted mean change | -1.35 Percent | Standard Error 0.174 |
95% CI: [-1.27, -0.37]Repeated Measures