Safety and Efficacy of Saxagliptin Plus Insulin With or Without Metformin
|Type 2 Diabetes||Drug: Saxagliptin, 5 mg + insulin Drug: Placebo + insulin||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||A Multicenter, Randomized, Double-Blind, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Insulin Alone or on Insulin in Combination With Metformin|
- Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF]) [ Time Frame: Baseline to Week 24 ]Change from baseline: post-pre. Adjusted for baseline (value and metformin use). ANCOVA model: difference between week t and baseline values=baseline values + treatment + metformin use
- Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT) [ Time Frame: Baseline to Week 24 ]An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal
- Change From Baseline in 120-minute PPG Values During an MTT [ Time Frame: Baseline to Week 24 ]An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal.
- Change From Baseline in Fasting Plasma Glucose Values [ Time Frame: Baseline to Week 24 ]
- Percentage of Participants Achieving a Therapeutic Glycemic Response [ Time Frame: Baseline to Week 24 ]Therapeutic glycemic response is defined as an A1C<7%. Significance was not interpreted with a p value.
- Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF) [ Time Frame: Baseline to Week 24 ]Based on information recorded in the participant's daily diary. The MTDDI was calculated at every visit using the values patients recorded since the last regularly scheduled visit (minimum of 80% of days with a value). At every visit, the MTDDI was compared with the participant's baseline MTDDI (measured during a 4-week lead-in period) to identify any changes in insulin use at that visit compared with insulin use at baseline.
- Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results [ Time Frame: Baseline to Week 52 ]ECG abnormalities included those in nonspecific "other" categories (Other nonspecific ST/T, Other intraventricular conduction defect, Other, and Other rhythm abnormalities)and nonspecific findings, such as sinus bradycardia, sinus arrythmia, sinus tachycardia, poor R-wave progression, and ventricular premature contractions.
- Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF) [ Time Frame: Baseline and Weeks 24 and 52 ]Absolute lymphocyte count=value*10^3 c/uL
- Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs [ Time Frame: Baseline to Week 52, continuously ]An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.
- Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings [ Time Frame: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52 ]
- Mean Changes From Baseline in Heart Rate [ Time Frame: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52 ]
- Shift in Platelet Counts From Baseline to Selected Visits (LOCF) [ Time Frame: Baseline and Weeks 24 and 52 ]Platelet count=value*10^9 c/L
- Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period [ Time Frame: Baseline and during and up to 14 days after last dose of study drug (in Week 52) ]
Marked abnormality=a laboratory value lying outside the predefined criteria and more extreme (farther from the limit)on-treatment than at baseline. ULN=upper limit of normal; LLN=lower limit of normal; prx=pre-RX=pretreatment.
Criteria 1: if prx=0 use >=2, if prx=0.5 or 1 use >=3, if prx=2 use 4.
- Percentage of Participants With Reported and Confirmed Hypoglycemia [ Time Frame: Baseline to Week 52 ]Confirmed hypoglycemia=fingerstick glucose measurement of ≤50 mg/dL with associated symptoms/
|Study Start Date:||November 2008|
|Study Completion Date:||April 2010|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
Experimental: Saxagliptin, 5 mg + insulin
Saxagliptin, 5 mg, plus insulin, administered to participants with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin
Drug: Saxagliptin, 5 mg + insulin
Saxagliptin, 5-mg tablets (plus stable insulin dose), given orally once daily (24 weeks short-term, 28 weeks long-term); participants stratified by use of stable metformin dose; flexible insulin dose (as needed for rescue)
Other Name: BMS-477118
Placebo Comparator: Placebo + insulin
Placebo administered to participants with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin
Drug: Placebo + insulin
Placebo tablets given orally once daily for 24 weeks (short-term period)+ insulin with metformin
Please refer to this study by its ClinicalTrials.gov identifier: NCT00757588
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|Study Director:||Bristol-Myers Squibb||Bristol-Myers Squibb|