Safety and Efficacy of Saxagliptin Plus Insulin With or Without Metformin

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00757588
First received: September 22, 2008
Last updated: October 4, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to compare the effects of saxagliptin with those of placebo as add-on therapy to insulin and insulin with metformin in improving glycemic control at 24 and 52 weeks.


Condition Intervention Phase
Type 2 Diabetes
Drug: Saxagliptin, 5 mg + insulin
Drug: Placebo + insulin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF]) [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Percentage of Participants Achieving a Therapeutic Glycemic Response [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Shift in Platelet Counts From Baseline to Selected Visits (LOCF) [ Time Frame: Baseline and Weeks 24 and 52 ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]
    Confirmed hypoglycemia=fingerstick glucose measurement of ≤50 mg/dL with associated symptoms/


Enrollment: 455
Study Start Date: November 2008
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 78 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes mellitus
  • Must have been taking a stable dose of basal or premixed insulin for 8 weeks or longer prior to screening
  • If taking metformin, must have been taking the same daily dose for 8 weeks or longer prior to screening
  • Insulin type should be intermediate- or long-acting (basal) or premixed (premixed formulation may include short- or rapid-acting insulin as 1 component).
  • Inadequate glycemic control (A1C of 7.5% to 11.0%, inclusive)
  • Body mass index of 45 kg/m² or lower
  • Fasting C-peptide level of 0.8 ng/mL or higher

Exclusion Criteria:

  • Symptoms of poorly controlled diabetes, including but not limited to marked polyuria and polydipsia with greater than 10% weight loss during the last 3 months prior to screening or other signs and symptoms
  • History of diabetic ketoacidosis or hyperosmolar nonketotic coma
  • Women of childbearing potential unable or unwilling to use acceptable birth control
  • Women who are pregnant or breastfeeding
  • Active liver disease
  • Anemia
  • Chronic or repeated intermittent corticosteroid treatment (participants receiving stable doses of replacement corticosteroid (except dexamethasone) therapy may be enrolled)
  • Use of short- or rapid-acting insulin
  • Significant cardiovascular history defined as: myocardial infarction, coronary angioplasty or bypass graft, valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accident
  • Congestive heart failure
  • Unstable or rapidly progressing renal disease
  • History of alcohol or drug abuse within the previous year
  • History of hemoglobinopathies
  • Unstable major psychiatric disorders
  • Immunocompromised status
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00757588

  Show 80 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00757588     History of Changes
Other Study ID Numbers: CV181-057, Eudract-2008-001089-10
Study First Received: September 22, 2008
Results First Received: August 10, 2011
Last Updated: October 4, 2013
Health Authority: United States: Food and Drug Administration
Russia: Ethics Committee
India: Central Drugs Standard Control Organization
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Brazil: National Health Surveillance Agency
South Africa: Medicines Control Council
Canada: Canadian Institutes of Health Research

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Saxagliptin
Insulin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014