Study of Multiple Doses of Saxagliptin (BMS-477118)

This study has been completed.
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00950599
First received: July 31, 2009
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

To evaluate the positive efficacy trend among doses of saxagliptin (BMS-477118) in subjects with Type 2 diabetes mellitus by assessing the change from baseline in HbA1c following 12 weeks of double-blind treatment.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Saxagliptin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: 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 Phase 2 Trial to Evaluate the Safety and Efficacy of BMS-477118 as Monotherapy in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Analysis of Test for Positive Efficacy Trend in Change From Baseline in Hemoglobin A1c (A1C) at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Positive efficacy trend among doses of saxagliptin by assessing the adjusted mean change from baseline in A1C in the 0-40 mg cohort. The unit of measurement for A1C is percent.

  • Change From Baseline in A1C at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in A1C achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.


Secondary Outcome Measures:
  • Change From Baseline in A1C at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in A1C achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in Fasting Serum Glucose (FSG) at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in FSG achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in FSG at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in FSG achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in Fructosamine at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in fructosamine achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in Fructosamine at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in fructosamine achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in Insulin at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in fasting insulin achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in Insulin at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in insulin achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in C-peptide at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in C-peptide achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in C-peptide at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in C-peptide achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in Postprandial Glucose 0-60 Minute Area Under the Curve (AUC) at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucose 0-60 minute AUC response to a liquid meal tolerance test (MTT) achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts. Area Under the Curve (AUC) here is defined as the area under the plot of the serum concentration of glucose against time after ingesting the meal for the first 60 minutes after the subject drinks the liquid meal.

  • Change From Baseline in Postprandial Glucose 0-60 Minute AUC at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucose 0-60 minute AUC response to a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort. Area Under the Curve (AUC) is defined as the area under the plot of plasma concentration of drug (not logarithm of the concentration) against time after drug administration. The AUC is of particular use in estimating bioavailability of drugs, and in estimating total clearance of drugs.

  • Change From Baseline in Postprandial Insulin 0-60 Minute AUC at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin 0-60 minute AUC response to a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts. Area Under the Curve (AUC) is defined as the area under the plot of plasma concentration of drug (not logarithm of the concentration) against time after drug administration. The AUC is of particular use in estimating bioavailability of drugs, and in estimating total clearance of drugs.

  • Change From Baseline in Postprandial Insulin 0-60 Minute AUC at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin 0-60 minute AUC response to a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort. Area Under the Curve (AUC) is defined as the area under the plot of plasma concentration of drug (not logarithm of the concentration) against time after drug administration. The AUC is of particular use in estimating bioavailability of drugs, and in estimating total clearance of drugs.

  • Change From Baseline in Postprandial C-peptide 0-60 Minute AUC at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide 0-60 minute AUC response to a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts. Area Under the Curve (AUC) is defined as the area under the plot of plasma concentration of drug (not logarithm of the concentration) against time after drug administration. The AUC is of particular use in estimating bioavailability of drugs, and in estimating total clearance of drugs.

  • Change From Baseline in Postprandial C-peptide 0-60 Minute AUC at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (postprandial) C-peptide 0-60 minute AUC response to a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort. Area Under the Curve (AUC) is defined as the area under the plot of plasma concentration of drug (not logarithm of the concentration) against time after drug administration. The AUC is of particular use in estimating bioavailability of drugs, and in estimating total clearance of drugs.

  • Change From Baseline in 15-minute Postprandial Glucose at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucose 15 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 30-minute Postprandial Glucose at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial glucose 30 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 60-minute Postprandial Glucose at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucose 60 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 15-minute Postprandial Glucose at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucose 15 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 30-minute Postprandial Glucose at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial glucose 30 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 60-minute Postprandial Glucose at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucose 60 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 15-minute Postprandial Insulin at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial insulin 15 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 30-minute Postprandial Insulin at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin 30 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 60-minute Postprandial Insulin at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin 60 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 15-minute Postprandial Insulin at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin 15 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 30-minute Postprandial Insulin at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin 30 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 60-minute Postprandial Insulin at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin 60 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 15-minute Postprandial C-peptide at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide 15 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 30-minute Postprandial C-peptide at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide 30 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 60-minute Postprandial C-peptide at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide 60 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 15-minute Postprandial C-peptide at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide 15 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 30-minute Postprandial C-peptide at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide 30 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 60-minute Postprandial C-peptide at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide 60 minutes after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 15-minute Postprandial Glucose Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucose excursion (15 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 30-minute Postprandial Glucose Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucose excursion (30 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 60-minute Postprandial Glucose Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucose excursion (60 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 15-minute Postprandial Glucose Excursion at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucose excursion (15 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 30-minute Postprandial Glucose Excursion at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucose excursion (30 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 60-minute Postprandial Glucose Excursion at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucose excursion (60 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 15-minute Postprandial Insulin Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin excursion (15 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 30-minute Postprandial Insulin Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin excursion (30 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 60-minute Postprandial Insulin Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin excursion (60 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 15-minute Postprandial Insulin Excursion at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin excursion (15 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 30-minute Postprandial Insulin Excursion at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin excursion (30 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 60-minute Postprandial Insulin Excursion at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) insulin excursion (60 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 15-minute Postprandial C-peptide Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide excursion (15 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 30-minute Postprandial C-peptide Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide excursion (30 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 60-minute Postprandial C-peptide Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide excursion (60 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 15-minute Postprandial C-peptide Excursion at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide excursion (15 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort

  • Change From Baseline in 30-minute Postprandial C-peptide Excursion at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide excursion (30 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 60-minute Postprandial C-peptide Excursion at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) C-peptide excursion (60 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin versus placebo at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 30-minute Postprandial Glucagon at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucagon 30 minutes after a MTT achieved at each dose of saxagliptin at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 30-minute Postprandial Glucagon at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucagon 30 minutes after a MTT achieved at each dose of saxagliptin at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 30-minute Postprandial Free Fatty Acids (FFA) at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) FFA 30 minutes after a MTT achieved at each dose of saxagliptin at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 30-minute Postprandial FFA at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) FFA 30 minutes after a MTT achieved at each dose of saxagliptin at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 30-minute Postprandial Glucagon Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucagon excursion (30 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 30-minute Postprandial Glucagon Excursion at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) glucagon excursion (30 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 30-minute Postprandial FFA Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) FFA excursion (30 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts.

  • Change From Baseline in 30-minute Postprandial FFA Excursion at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial (after mealtime) FFA excursion (30 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin at Week 12 in the 0-40 mg cohort.

  • Change From Baseline in 15-minute Insulinogenic Index at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Mean change from baseline in 15-minute insulinogenic index of a MTT achieved at each dose of saxagliptin at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts. The insulinogenic index is a unitless scale which is a measure of insulin production normalized for the glucose stimulus. Higher numbers mean more beta cell function (improvement). The low value is zero. The highest value obtainable is unknown.

  • Change From Baseline in 15-minute Insulinogenic Index at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Mean change from baseline in 15-minute insulinogenic index of a MTT achieved at each dose of saxagliptin at Week 12 in the 0-40 mg cohort. The insulinogenic index is a unitless scale which is a measure of insulin production normalized for the glucose stimulus. Higher numbers mean more beta cell function (improvement). The low value is zero. The highest value obtainable is unknown.

  • Change From Baseline in 30-minute Insulinogenic Index at Week 6 in the 0-40 and 0 & 100 mg Cohorts. [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Mean change from baseline in 30-minute insulinogenic index of a MTT achieved at each dose of saxagliptin at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts. The insulinogenic index is a unitless scale which is a measure of insulin production normalized for the glucose stimulus. Higher numbers mean more beta cell function (improvement). The low value is zero. The highest value obtainable is unknown.

  • Change From Baseline in 30-minute Insulinogenic Index at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Mean change from baseline in 30-minute insulinogenic index of a MTT achieved at each dose of saxagliptin at Week 12 in the 0-40 mg cohort. The insulinogenic index is a unitless scale which is a measure of insulin production normalized for the glucose stimulus. Higher numbers mean more beta cell function (improvement). The low value is zero. The highest value obtainable is unknown.

  • Change From Baseline in Matsuda Index at Week 6 in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Mean change from baseline in Matsuda index achieved at each dose of saxagliptin at Week 6 in the 0-40 mg and the 0 & 100 mg cohorts. The Matsuda index is a scale designed to give numbers between 0 and 12, with a linear relationship to other indices of insulin sensitivity. The higher the number, the better the insulin sensitivity (improvement).

  • Change From Baseline in Matsuda Index at Week 12 in the 0-40 mg Cohort [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Mean change from baseline in Matsuda index achieved at each dose of saxagliptin at Week 12 in the 0-40 mg cohort. The Matsuda index is a scale designed to give numbers between 0 and 12, with a linear relationship to other indices of insulin sensitivity. The higher the number, the better the insulin sensitivity (improvement).

  • Change From Baseline in A1C at 2 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 14 ] [ Designated as safety issue: No ]
    Mean change from baseline in A1C achieved at each dose of saxagliptin during the Follow-Up period at Week 14 in the 0-40 mg cohort and at Week 8 in the 0 & 100 mg cohort.

  • Change From Baseline in A1C at 4 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 10, Week 16 ] [ Designated as safety issue: No ]
    Mean change from baseline in A1C achieved at each dose of saxagliptin during the Follow-Up period at Week 16 in the 0-40 mg cohort and at Week 10 in the 0 & 100 mg cohort.

  • Change From Baseline in FSG at 2 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 8, Week 14 ] [ Designated as safety issue: No ]
    Mean change from baseline in FSG achieved at each dose of saxagliptin during Follow-Up period at Week 14 in the 0-40 mg cohort and at Week 8 in the 0 & 100 mg cohort.

  • Change From Baseline in FSG at 4 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 10, Week 16 ] [ Designated as safety issue: No ]
    Mean change from baseline in FSG achieved at each dose of saxagliptin during the follow-up period at Week 16 in the 0-40 mg cohort and at Week 10 in the 0 & 100 mg cohort.

  • Change From Baseline in Fructosamine at 2 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 8, Week 14 ] [ Designated as safety issue: No ]
    Mean change from baseline in fructosamine achieved at each dose of saxagliptin during the Follow-up period at Week 14 in the 0-40 mg cohort and at Week 8 in the 0 & 100 mg cohort.

  • Change From Baseline in Fructosamine at 4 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts [ Time Frame: Baseline, Week 10, Week 16 ] [ Designated as safety issue: No ]
    Mean change from baseline in fructosamine achieved at each dose of saxagliptin during the Follow-up period at Week 16 in the 0-40 mg cohort and at Week 10 in the 0 & 100 mg cohort.

  • Change From Baseline in A1C at Week 6 by Baseline A1C Category in the 0 & 100 Cohort [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in A1C achieved at each dose of saxagliptin at Week 6 in subjects with baseline A1C <7%, ≥7% to <8%, ≥8% to <9%, and ≥9% in the 0 & 100 mg cohort.

  • Change From Baseline in FSG at Week 6 in Subjects by Baseline FSG Category in the 0 & 100 mg Cohort. [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in FSG achieved at each dose of saxagliptin at Week 6 in subjects with baseline FSG <140 mg/dL, ≥140 mg/dL to <180 mg/dL, and ≥ 180 mg/dL in the 0 & 100 mg cohort.

  • Change From Baseline in 60 Minute Postprandial Glucose at Week 6 by Baseline Category in the 0 & 100 mg Cohort [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in 60-minute postprandial glucose achieved at each dose of saxagliptin at Week 6 in subjects with baseline 60-minute postprandial glucose <140 mg/dL, ≥140 to <200 mg/dL, and ≥200 mg/dL in the 0 & 100 mg cohort.

  • Percentage of Participants Achieving A1C < 7% at Week 6 in the 0 & 100 mg Cohort [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    Percentage of participants achieving A1C < 7%, the American Diabetic Association's defined goal for glycemia, at each dose of saxagliptin at Week 6 in the 0 & 100 mg cohort.

  • Change From Baseline in 60-minute Postprandial FFA Excursion at Week 6 in the 0 & 100 mg Cohort [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial FFA excursion (60 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin at Week 6 in the 0 & 100 mg cohort. (Note: this analysis was not performed.)

  • Change From Baseline in 60-minute Postprandial Glucagon Excursion at Week 6 in the 0 & 100 mg Cohort [ Time Frame: Baseline, Week 6 ] [ Designated as safety issue: No ]
    Adjusted mean change from baseline in postprandial glucagon excursion (60 minutes minus 0 minutes) after a MTT achieved at each dose of saxagliptin at Week 6 in the 0 & 100 mg cohort. (Note: this analysis was not performed.)

  • Discontinuations During the Double-Blind Phase Due to Lack of Glycemic Control [ Time Frame: Week 4, Week 6 ] [ Designated as safety issue: No ]
    Number of participants discontinuing from the double-blind phase due to lack of glycemic control at Week 4 and Week 6. (Note: this analysis was not performed.)

  • Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations During the Double-Blind Treatment Period in the 0-40 mg Cohort [ Time Frame: up to Week 12 for AEs; up to 30 days post-double-blind period but prior to follow-up period if any for SAEs and up to 30 days post-double-blind period for Discontinuations ] [ 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. Related AE=relationship of certain, probable, possible, or missing. 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 the development of drug dependency or drug abuse, is an important medical event.

  • Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations During the Double-Blind Treatment Period in the 0 & 100 mg Cohort [ Time Frame: up to Week 6 for AEs; up to 30 days post-double-blind period but prior to follow-up period if any for SAEs and up to 30 days post-double-blind period for Discontinuations ] [ 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. Related AE=relationship of certain, probable, possible, or missing. 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 the development of drug dependency or drug abuse, is an important medical event.

  • Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations During the Follow-up Period in the 0-40 mg Cohort [ Time Frame: From Week 12 to Week 16 for AEs; up to 30 days post follow-up in both cohorts for SAEs and Discontinuations ] [ 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. Related AE=relationship of certain, probable, possible, or missing. 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 the development of drug dependency or drug abuse, is an important medical event.

  • Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations During the Follow-up Period in the 0 & 100 mg Cohort [ Time Frame: From Week 6 to Week 10 for AEs; up to 30 days post follow-up in both cohorts for SAEs and Discontinuations ] [ 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. Related AE=relationship of certain, probable, possible, or missing. 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 the development of drug dependency or drug abuse, is an important medical event.


Enrollment: 423
Study Start Date: May 2003
Study Completion Date: May 2004
Primary Completion Date: May 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Saxagliptin (2.5 mg) Drug: Saxagliptin
Tablets, Oral, 2.5 mg, once daily, 12 weeks
Other Name: BMS-477118
Experimental: Saxagliptin (5 mg) Drug: Saxagliptin
Tablets, Oral, 5 mg, once daily, 12 weeks
Other Name: BMS-477118
Experimental: Saxagliptin (10 mg) Drug: Saxagliptin
Tablets, Oral, 10 mg, once daily, 12 weeks
Other Name: BMS-477118
Experimental: Saxagliptin (20 mg) Drug: Saxagliptin
Tablets, Oral, 20 mg, once daily, 12 weeks
Other Name: BMS-477118
Experimental: Saxagliptin (40 mg) Drug: Saxagliptin
Tablets, Oral, 40 mg, once daily, 12 weeks
Other Name: BMS-477118
Experimental: Saxagliptin (100 mg) Drug: Saxagliptin
Tablets, Oral, 100 mg, once daily, 6 weeks
Other Name: BMS-477118
Placebo Comparator: Placebo Drug: Placebo
Tablets, Oral, 0 mg, once daily, 6 and 12 weeks

  Eligibility

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 diabetes who are drug-naive
  • Screening HbA1c ≥ 6.8% and ≤ 9.7%
  • Screening fasting or random C-peptide > 0.5 ng/mL
  • < 35 years old must be negative for anti-GAD antibodies
  • Body Mass Index < 35 kg/m2

Exclusion Criteria:

  • Symptoms of poorly controlled diabetes
  • History of diabetic ketoacidosis, hyperosmolar nonketotic coma, or insulin therapy within one year of screening
  • Receipt of oral antihyperglycemic medications for more than six months in total since diagnosis
  • Significant cardiovascular history
  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: NCT00950599

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

Publications:
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00950599     History of Changes
Other Study ID Numbers: CV181-008
Study First Received: July 31, 2009
Results First Received: August 28, 2009
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 23, 2014