Clinical trial NCT00950599: Study of Multiple Doses of Saxagliptin (BMS-477118)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2009-08-03
Enrollment: 423
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Analysis of Test for Positive Efficacy Trend in Change From Baseline in Hemoglobin A1c (A1C) at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in A1C at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in A1C at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in Fasting Serum Glucose (FSG) at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in FSG at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in Fructosamine at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in Fructosamine at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in Insulin at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in Insulin at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in C-peptide at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in C-peptide at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: 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
timeFrame: Baseline, Week 6
measure: Change From Baseline in Postprandial Glucose 0-60 Minute AUC at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in Postprandial Insulin 0-60 Minute AUC at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in Postprandial Insulin 0-60 Minute AUC at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in Postprandial C-peptide 0-60 Minute AUC at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in Postprandial C-peptide 0-60 Minute AUC at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 15-minute Postprandial Glucose at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 30-minute Postprandial Glucose at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 60-minute Postprandial Glucose at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 15-minute Postprandial Glucose at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 30-minute Postprandial Glucose at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 60-minute Postprandial Glucose at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 15-minute Postprandial Insulin at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 30-minute Postprandial Insulin at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 60-minute Postprandial Insulin at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 15-minute Postprandial Insulin at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 30-minute Postprandial Insulin at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 60-minute Postprandial Insulin at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 15-minute Postprandial C-peptide at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 30-minute Postprandial C-peptide at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 60-minute Postprandial C-peptide at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 15-minute Postprandial C-peptide at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 30-minute Postprandial C-peptide at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 60-minute Postprandial C-peptide at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 15-minute Postprandial Glucose Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 30-minute Postprandial Glucose Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 60-minute Postprandial Glucose Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 15-minute Postprandial Glucose Excursion at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 30-minute Postprandial Glucose Excursion at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 60-minute Postprandial Glucose Excursion at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 15-minute Postprandial Insulin Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 30-minute Postprandial Insulin Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 60-minute Postprandial Insulin Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 15-minute Postprandial Insulin Excursion at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 30-minute Postprandial Insulin Excursion at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 60-minute Postprandial Insulin Excursion at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 15-minute Postprandial C-peptide Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 30-minute Postprandial C-peptide Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 60-minute Postprandial C-peptide Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 15-minute Postprandial C-peptide Excursion at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 30-minute Postprandial C-peptide Excursion at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 60-minute Postprandial C-peptide Excursion at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 30-minute Postprandial Glucagon at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 30-minute Postprandial Glucagon at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 30-minute Postprandial Free Fatty Acids (FFA) at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 30-minute Postprandial FFA at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 30-minute Postprandial Glucagon Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 30-minute Postprandial Glucagon Excursion at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 30-minute Postprandial FFA Excursion at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 30-minute Postprandial FFA Excursion at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 15-minute Insulinogenic Index at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in 15-minute Insulinogenic Index at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in 30-minute Insulinogenic Index at Week 6 in the 0-40 and 0 & 100 mg Cohorts.
timeFrame: Baseline, Week 6
measure: Change From Baseline in 30-minute Insulinogenic Index at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in Matsuda Index at Week 6 in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 6
measure: Change From Baseline in Matsuda Index at Week 12 in the 0-40 mg Cohort
timeFrame: Baseline, Week 12
measure: Change From Baseline in A1C at 2 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 14
measure: Change From Baseline in A1C at 4 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 10, Week 16
measure: Change From Baseline in FSG at 2 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 8, Week 14
measure: Change From Baseline in FSG at 4 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 10, Week 16
measure: Change From Baseline in Fructosamine at 2 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 8, Week 14
measure: Change From Baseline in Fructosamine at 4 Weeks After Discontinuation of Double-Blind Study Medication in the 0-40 and 0 & 100 mg Cohorts
timeFrame: Baseline, Week 10, Week 16
measure: Change From Baseline in A1C at Week 6 by Baseline A1C Category in the 0 & 100 Cohort
timeFrame: Baseline, Week 6
measure: Change From Baseline in FSG at Week 6 in Subjects by Baseline FSG Category in the 0 & 100 mg Cohort.
timeFrame: Baseline, Week 6
measure: Change From Baseline in 60 Minute Postprandial Glucose at Week 6 by Baseline Category in the 0 & 100 mg Cohort
timeFrame: Baseline, Week 6
measure: Percentage of Participants Achieving A1C < 7% at Week 6 in the 0 & 100 mg Cohort
timeFrame: Week 6
measure: Change From Baseline in 60-minute Postprandial FFA Excursion at Week 6 in the 0 & 100 mg Cohort
timeFrame: Baseline, Week 6
measure: Change From Baseline in 60-minute Postprandial Glucagon Excursion at Week 6 in the 0 & 100 mg Cohort
timeFrame: Baseline, Week 6
measure: Discontinuations During the Double-Blind Phase Due to Lack of Glycemic Control
timeFrame: Week 4, Week 6
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: From Week 12 to Week 16 for AEs; up to 30 days post follow-up in both cohorts for SAEs and Discontinuations
measure: 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
timeFrame: From Week 6 to Week 10 for AEs; up to 30 days post follow-up in both cohorts for SAEs and Discontinuations
Other outcomes:
Locations:
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Rosenstock J, Sankoh S, List JF. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab. 2008 May;10(5):376-86. doi: 10.1111/j.1463-1326.2008.00876.x. Epub 2008 Mar 18.