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

• ClinicalTrials.gov Identifier: NCT00374907
• Recruitment Status: Completed
• First Posted: September 12, 2006
• Results First Posted: January 21, 2011
• Last Update Posted: May 7, 2015
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Type 2 Diabetes	Drug: Saxagliptin; Drug: Placebo; Drug: Metformin (blinded); Drug: Metformin (open-label)	Phase 3

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 156 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Mechanism of Action and Efficacy of Saxagliptin (BMS-477118) in the Treatment of Type 2 Diabetic Patients
• Study Start Date: September 2006
• Actual Primary Completion Date: January 2008
• Actual Study Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
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)

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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 :

1. Insulin Secretion Rate AUC During IV Hyperglycemic Clamp - Percent Change From Baseline at Week 12 [ Time Frame: Baseline, Week 12 ]
   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:

1. Overall Summary of Adverse Events (AEs) Serious AEs (SAEs), Discontinuations, and Deaths During the ST + LT Treatment Period [ Time Frame: 116 weeks ]
   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.
2. Marked Laboratory Abnormalities - During ST + LT Treatment Period [ Time Frame: 116 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00374907
• Other Study ID Numbers: CV181-041
• First Posted: September 12, 2006
• Results First Posted: January 21, 2011
• Last Update Posted: May 7, 2015
• Last Verified: March 2015

Additional relevant MeSH terms:

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