Safety and Efficacy of Saxagliptin Plus Insulin With or Without Metformin
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|ClinicalTrials.gov Identifier: NCT00757588|
Recruitment Status : Completed
First Posted : September 23, 2008
Results First Posted : December 13, 2011
Last Update Posted : June 1, 2015
|Condition or disease||Intervention/treatment||Phase|
|Type 2 Diabetes||Drug: Saxagliptin, 5 mg + insulin Drug: Placebo + insulin||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||455 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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|
|Study Start Date :||November 2008|
|Actual Primary Completion Date :||April 2010|
|Actual Study Completion Date :||April 2010|
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
- 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/
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00757588
|Study Director:||Bristol-Myers Squibb||Bristol-Myers Squibb|