Efficacy and Safety Study of Saxagliptin + Metformin Immediate Release (IR) Versus Metformin IR Alone in Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00885378
First received: April 21, 2009
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to compare the reduction in hemoglobin A1C (A1C) for participants taking saxagliptin in combination with metformin immediate release (IR) versus metformin IR alone.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Saxagliptin plus metformin IR
Drug: Placebo plus metformin IR
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Trial to Evaluate the Efficacy and Safety of 2.5 mg Saxagliptin, Twice Daily, in Combination With Metformin IR in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin IR Alone

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Mean Hemoglobin A1C (A1c) and Change From Baseline to Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Mean change was adjusted for baseline.


Secondary Outcome Measures:
  • Mean Baseline and Change From Baseline in Fasting Plasma Glucose (FPG) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Mean change was adjusted for baseline.

  • Percentage of Participants Achieving a Therapeutic Glycemic Response (A1C < 7.0%) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Adjusted for baseline. Calculated using the method by Zhang et al. (Zhang M, Tsiatis A, Davidian M. Improving efficiency of inference in randomized clinical trials using auxiliary covariates. Biometrics. Published online on January 11, 2008; Digital Object Identifier: 10.1111/j.1541-0420.2007.00976.x.)

  • Percentage of Participants Achieving a Therapeutic Glycemic Response (A1C <= 6.5%) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Adjusted for baseline. Calculated using the method by Zhang et al. (Zhang M, Tsiatis A, Davidian M. Improving efficiency of inference in randomized clinical trials using auxiliary covariates. Biometrics. Published online on January 11, 2008; Digital Object Identifier: 10.1111/j.1541-0420.2007.00976.x.)


Other Outcome Measures:
  • Participant Adverse Event (AE), Related AE, Serious Adverse Event (SAE), Related SAE, and Discontinued Due to AEs Summary [ Time Frame: Week 1 to Week 12; AEs are included up to the last treatment day + 1 day or the last visit in the double-blind (DB) period. SAEs are included up to the last of 1) the last treatment day + 30 days or 2) the last visit day + 30 days in the DB period. ] [ Designated as safety issue: Yes ]
    AE = any new untoward medical occurrence/worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment.SAE = any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Treatment-related=Possible, Probable, or Certain relationship to drug.

  • Participants With Reported Hypoglycemia AEs During Double-Blind Treatment Period [ Time Frame: Week 1 to Week 12; AEs are included up to the last treatment day + 1 day or the last visit in the DB period. SAEs are included up to the last of 1) the last treatment day + 30 days or 2) the last visit day + 30 days in the DB period. ] [ Designated as safety issue: Yes ]
    Hypoglycemic Events are based upon the Saxagliptin Predefined List of Events, which included hypoglycemia, blood glucose decreased, and hypoglycemic unconsciousness.

  • Participants With Confirmed Hypoglycemia [ Time Frame: Week 1 to Week 12; AEs are included up to the last treatment day + 1 day or the last visit in the DB period. SAEs are included up to the last of 1) the last treatment day + 30 days or 2) the last visit day + 30 days in the DB period. ] [ Designated as safety issue: Yes ]
    Confirmed hypoglycemia was defined by a fingerstick glucose value <= 50 mg/dL with associated hypoglycemia symptoms.

  • Participant Electrocardiogram (ECG) Status at Baseline and Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: Yes ]
    Abnormal ECGs were defined as those not within the normal limits for the participant, according to the investigator. 'Shifted Normal to Abnormal' and 'Shifted Abnormal to Normal' references a change from measurements at Baseline to those at Week 12.

  • Baseline and Mean Change From Baseline in Participant Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: Baseline, Week 4, Week 8, Week 12 ] [ Designated as safety issue: Yes ]
    Baseline values reference the measurement for the cohort of participants evaluated at the given time point.

  • Baseline and Mean Change From Baseline in Participant Heart Rate (HR) [ Time Frame: Baseline, Week 4, Week 8, Week 12 ] [ Designated as safety issue: Yes ]
    Baseline values reference the measurement for the cohort of participants evaluated at the given time point.

  • Participants Experiencing Changes From Baseline in Laboratory Parameters That Met the Marked Abnormality Criteria [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: Yes ]
    A laboratory value was considered a marked abnormality if it is outside the pre-defined criteria for marked abnormality and the on-treatment value was more extreme (farther from the limit) than the baseline value. ULN=upper limit of normal; LLN=lower limit of normal.

  • Participants Experiencing Changes From Baseline in Urinalysis Parameters That Met the Marked Abnormality Criteria [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: Yes ]
    Marked abnormality criteria were urine protein: if pre-Rx=o use >=2, if pre-Rx =0.5 or 1 use >=3, if pre-Rx =2, use >=4; urine blood: if pre-Rx=0, use >=2, if pre-Rx=0.5 or 1, use >=3, if pre-Rx=2, use >=4; Urine red blood cell count (RBC): if pre-Rx=o use >=2, if pre-Rx =0.5 or 1 use >=3, if pre-Rx =2, use >=4; urine white blood cell count (WBC): if pre-Rx=o use >=2, if pre-Rx =0.5 or 1 use >=3, if pre-Rx =2, use >=4.


Enrollment: 166
Study Start Date: May 2009
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Saxagliptin plus metformin IR Drug: Saxagliptin plus metformin IR
Tablets, Oral, 2.5 mg, Twice daily, 12 weeks
Other Names:
  • BMS-477118
  • Onglyza
Placebo Comparator: Placebo plus metformin IR Drug: Placebo plus metformin IR
Tablets, Oral, Placebo, Twice daily, 12 weeks

  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
  • 18-78 years of age
  • Taking stable twice daily (BID) dosing of metformin IR (at least 1500 mg) for at least 8 weeks
  • A1C: 7-10%
  • C-peptide: ≥ 0.8 ng/mL
  • Body mass index (BMI): ≤45 kg/m^2

Exclusion Criteria:

  • Women of childbearing potential unable or unwilling to use acceptable birth control
  • Women who are pregnant or breastfeeding
  • Fasting plasma glucose (FPG) >270 mg/dL
  • Significant cardiovascular history
  • Symptoms of poorly controlled diabetes
  • History of diabetic ketoacidosis or hyperosmolar nonketotic coma
  • Insulin therapy within one year of screening
  • Cardiovascular even within the prior 6 months
  • New York Heart Association Stage III/IV congestive heart failure and/or known left ventricular ejection fraction <=40%
  • Significant history of renal or hepatic disease
  • History of a psychiatric disorder, alcohol or drug abuse within the previous year
  • Treatment with potent CYP3A4 inhibitors or inducers
  • Immunocompromised participants
  • Active liver disease or clinically significant abnormal hepatic, renal , endocrine, metabolic, or hematological screening tests
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00885378

  Show 41 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00885378     History of Changes
Other Study ID Numbers: CV181-080, EUDRACT #: 2009-010224-25
Study First Received: April 21, 2009
Results First Received: November 2, 2011
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission
Hungary: National Institute of Pharmacy
Hungary: Medical Research Council Ethic Committee for Clinical Pharmacology (MRC-ECCP)
Mexico: Federal Commission for Sanitary Risks Protection
Mexico: Ethics Committee

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

ClinicalTrials.gov processed this record on October 23, 2014