A Study Assessing Saxagliptin Treatment in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00374907
First received: September 7, 2006
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

The purpose of this clinical research study is to learn whether Saxagliptin can improve the body's ability to make its own insulin and lower blood sugar in people with type 2 diabetes


Condition Intervention Phase
Type 2 Diabetes
Drug: Saxagliptin
Drug: Placebo
Drug: Metformin (blinded)
Drug: Metformin (open-label)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Mechanism of Action and Efficacy of Saxagliptin (BMS-477118) in the Treatment of Type 2 Diabetic Patients

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Insulin Secretion Rate Area Under the Curve (AUC) During Intravenous (IV)-Oral Hyperglycemic Clamp - Percent Change From Baseline at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted percent change in the insulin secretion rate AUC during a hyperglycemic clamp with an enteral glucose load [intravenous-oral hyperglycemic clamp (180-480 minutes)] at Week 12. The method used for calculating the insulin secretion rate was C-peptide deconvolution.


Secondary Outcome Measures:
  • Insulin Secretion Rate AUC During IV Hyperglycemic Clamp - Percent Change From Baseline at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted percent change in the insulin secretion rate AUC during an intravenous hyperglycemic clamp (120-180 minutes) at Week 12. The method used for calculating the insulin secretion rate was C-peptide deconvolution.


Other Outcome Measures:
  • Overall Summary of Adverse Events (AEs) Serious AEs (SAEs), Discontinuations, and Deaths During the ST + LT Treatment Period [ Time Frame: 116 weeks ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or 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. Related events=relationship of certain, probable, possible, or missing.

  • Marked Laboratory Abnormalities - During ST + LT Treatment Period [ Time Frame: 116 weeks ] [ 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. Pre-Rx=pretreatment; ULN=upper limit of normal; ALP=alkaline phosphatase; AST=aspartate aminotransferase; ALT=alanine aminotransferase; BUN=blood urea nitrogen; unspec.=unspecified; sodium serum low: <0.9 x Pre-Rx & <=130mEq/L / high: >1.1 x Pre-Rx & >=150mEq/L; potassium, serum low: <=0.8 x Pre-Rx & >=6.0mEq/L / high: 1.2 x Pre-Rx & >=6.0mEq/L; LLN=lower limit of normal.


Enrollment: 156
Study Start Date: September 2006
Study Completion Date: December 2009
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Saxagliptin (A)
Metformin 500-1500 mg (open-label, as needed for rescue in LT)
Drug: Saxagliptin
Tablet, Oral, 5 mg, Once daily, (up to 12 weeks ST, up to 104 weeks LT)
Other Name: BMS-477118
Placebo Comparator: Placebo (ST) / Metformin (LT) (B)
Metformin 500-1500 mg (open-label, as needed for rescue in LT)
Drug: Placebo
Tablet, Oral, 0 mg, Once daily (up to 12 weeks ST)
Drug: Metformin (blinded)
Tablet, Oral, 500 mg titrated to 1000 mg, Once daily (up to 104 weeks LT, starting at Week 12)
Drug: Metformin (open-label)
Tablets, Oral, 500-1500 mg, as needed (starting in LT)

Detailed Description:

All subjects will participate in a lead-in period, and qualifying subjects will continue into a short-term randomized treatment period. Subjects who complete the short-term period will be eligible to enter the long term extension period. Also, subjects who have an elevated blood sugar that requires additional medication for blood sugar control will be eligible to receive open-label metformin added onto their blinded study medication

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes mellitus
  • Drug naive
  • Hemoglobin A1c (HbA1c) ≥6.0% and ≤8.0%
  • Fasting C-peptide ≥1.0 ng/mL
  • Body mass index ≤40 kg/m²

Exclusion Criteria:

  • Recent cardiac or cerebrovascular event
  • Elevated serum creatinine
  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: NCT00374907

Locations
United States, California
Va San Diego Healthcare System
San Diego, California, United States, 92161
United States, Louisiana
Pennington Biomedical Research Center
Baton Rouge, Louisiana, United States, 70808
United States, Texas
Diabetes & Glandular Disease Research Assoc,, Inc.
San Antonio, Texas, United States, 78229
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: NCT00374907     History of Changes
Other Study ID Numbers: CV181-041
Study First Received: September 7, 2006
Results First Received: December 26, 2010
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 18, 2014