Official Title: “"A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial to Evaluate the Efficacy and Safety of BMS-477118 in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone"”

The purpose of this clinical research study is to learn whether Saxagliptin added to Metformin therapy is more effective than Metformin alone as a treatment for type 2 diabetic subjects who are not sufficiently controlled with Metformin alone

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2006

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 in the short-term period who have an elevated blood sugar that requires additional medication for blood sugar control will be eligible to enter the long-term treatment extension period where they will receive pioglitizone added onto their blinded study medication

Intervention(s) in this Clinical Trial

• Drug: Saxagliptin + Metformin
  • Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)
• Drug: Saxagliptin + Metformin
  • Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)
• Drug: Saxagliptin + Metformin
  • Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)
• Drug: Placebo + Metformin
  • Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT)
• Drug: Pioglitazone
  • Tablets, Oral, 15 - 45 mg (as needed for rescue)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Saxagliptin + Metformin (A)
  • Pioglitazone 15-45 mg (as needed for rescue)
• Experimental: Saxagliptin + Metformin (B)
  • Pioglitazone 15-45 mg (as needed for rescue)
• Experimental: Saxagliptin + Metformin (C)
  • Pioglitazone 15-45 mg (as needed for rescue)
• Placebo Comparator: Placebo+ Metformin (D)
  • Pioglitazone 15-45 mg (as needed for rescue)

Primary Measures

• Change from baseline in HbA1c to week 24 with each dose of BMS-477118 plus metformin vs placebo plus metformin
  • Time Frame: week 24
    Safety Issue?: No

Secondary Measures

• Change from baseline at week 24 in the area under the curve in post-prandial assessments
  • Time Frame: week 24
    Safety Issue?: No
• To assess for each BMS-477118 treatment group the glycemic parameters in the long-term extension
  • Time Frame: in the long-term extension
    Safety Issue?: No
• To assess the safety and tolerability of each dose of BMS-477118 when administered for up to 4 years
  • Time Frame: when administered for up to 4 years
    Safety Issue?: Yes
• To assess the safety and tolerability of each dose of BMS-477118 plus metformin when administered for up to 42 months
  • Time Frame: when administered for up to 42 months
    Safety Issue?: Yes

Inclusion Criteria:

• Type 2 diabetes mellitus requiring treatment with at least 1500 mg but not greater than 2550 mg of a maximum tolerated dose of Metformin therapy for at least 8 weeks prior to screening.
• HbA1c >= 7.0% and <= 10.0 %
• Body mass index <= 40 kg/m2
• Fasting C-peptide >= 1ng/dL
• women or child bearing potential

Exclusion Criteria:

• Symptomatic poorly controlled diabetes
• Recent cardiac or cerebrovascular event
• Serum creatinine >= 1.5 mg/dL for males and >= 1.4 mg/dL for females

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 77 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Bristol-Myers Squibb

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00121667

Study ID Number: CV181-014

ClinicalTrials.gov Identifier: NCT00121667

Health Authority: United States: Food and Drug Administration

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