A Study of Saxagliptin in Subjects With Type 2 Diabetes Who Have Inadequate Blood Sugar Control With Sulfonylureas

• ClinicalTrials.gov Identifier: NCT00313313
• Recruitment Status: Completed
• First Posted: April 12, 2006
• Results First Posted: September 25, 2009
• Last Update Posted: May 4, 2015
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: April 10, 2006
• First Posted Date: April 12, 2006
• Results First Submitted Date: August 17, 2009
• Results First Posted Date: September 25, 2009
• Last Update Posted Date: May 4, 2015
• Study Start Date: April 2006
• Actual Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2009)

Change From Baseline in Hemoglobin A1c (A1C) at Week 24 [ Time Frame: Baseline, Week 24 ]

Mean change from baseline in A1C at Week 24, adjusted for baseline value.

• Original Primary Outcome Measures (submitted: April 11, 2006): Change in baseline A1C value after 24 weeks of treatment.

Current Secondary Outcome Measures (submitted: October 5, 2009)

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 [ Time Frame: Baseline, Week 24 ]
  Mean change from baseline in FPG at Week 24, adjusted for baseline value.
• Percentage of Participants Achieving A1C < 7% at Week 24 [ Time Frame: Week 24 ]
  Percentage of participants achieving A1C < 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus glyburide versus placebo plus upward titrated glyburide at Week 24.
• Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 [ Time Frame: Baseline, Week 24 ]
  Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjusted for baseline values.

Original Secondary Outcome Measures (submitted: April 11, 2006)

• Change from baseline in fasting plasma glucose.
• Proportion of subjects achieving A1C < 7%.
• Changes from baseline in area under the curve for postprandial glucose response to an oral glucose tolerance test.
• Proportion of subjects who rescue or discontinue for lack of efficacy.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Saxagliptin in Subjects With Type 2 Diabetes Who Have Inadequate Blood Sugar Control With Sulfonylureas
• Official Title: A Multicenter, Randomized, Double-Blind Placebo-Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination With Glyburide in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Glyburide Alone
• Brief Summary: The purpose of this trial is to understand if adding saxagliptin to a sulfonylurea is safe and works better than increasing the amount of sulfonylurea a patient takes
• 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 in the short-term period who have an elevated blood sugar that requires additional medication for blood sugar control (defined as rescue) will be eligible to enter the long-term treatment extension period where they will receive metformin.Rescue treatment with metformin is also available during the long-term extension period for subjects who meet glycemic criteria.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Diabetes

Intervention

• Drug: Saxagliptin
  Tablets, Oral, 2.5 mg, Daily AM, (24 weeks short-term [ST], 12 months long-term [LT])
  Other Name: BMS-477118
• Drug: Saxagliptin
  Tablets, Oral, 5 mg, Daily AM (24 weeks ST, 12 months LT).
  Other Name: BMS-477118
• Drug: Glyburide
  Capsules, Oral, OL, 7.5 mg, Daily, AM (24 weeks ST, 12 months LT)
• Drug: Placebo
  Tablets, Oral, 0 mg, Daily AM/PM, (24 weeks ST, 12 months LT)
• Drug: Glyburide
  Capsules, Oral, DB Glyburide, 2.5 mg titrated to 7.5 mg + 7.5 mg OL, Daily AM/PM (24 weeks ST, 12 months LT)
• Drug: Metformin
  Tablets, Oral, OL, 500 - 2500 mg, 1 or 2 times per day (12 months LT)

Study Arms

• Experimental: Saxagliptin 2.5 mg + Glyburide 7.5 mg (A)
  Metformin 500-2500 mg (as needed)
  Interventions:

  • Drug: Saxagliptin
  • Drug: Glyburide
  • Drug: Metformin
• Experimental: Saxagliptin 5 mg + Glyburide 7.5 mg (B)
  Metformin 500-2500 mg (as needed)
  Interventions:

  • Drug: Saxagliptin
  • Drug: Glyburide
  • Drug: Metformin
• Placebo Comparator: Placebo + Glyburide 7.5 mg (C)
  Metformin 500-2500 mg (as needed)
  Interventions:

  • Drug: Placebo
  • Drug: Glyburide
  • Drug: Metformin

Publications *

• Chacra AR, Tan GH, Apanovitch A, Ravichandran S, List J, Chen R; CV181-040 Investigators. Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Pract. 2009 Sep;63(9):1395-406. doi: 10.1111/j.1742-1241.2009.02143.x. Epub 2009 Jul 15. Erratum In: Int J Clin Pract. 2010 Jan;64(2):277.
• Perl S, Cook W, Wei C, Iqbal N, Hirshberg B. Saxagliptin Efficacy and Safety in Patients With Type 2 Diabetes and Moderate Renal Impairment. Diabetes Ther. 2016 Sep;7(3):527-35. doi: 10.1007/s13300-016-0184-9. Epub 2016 Jul 11.
• Bonora E, Bryzinski B, Hirshberg B, Cook W. A post hoc analysis of saxagliptin efficacy and safety in patients with type 2 diabetes stratified by UKPDS 10-year cardiovascular risk score. Nutr Metab Cardiovasc Dis. 2016 May;26(5):374-9. doi: 10.1016/j.numecd.2015.11.004. Epub 2015 Dec 1.
• Karyekar CS, Frederich R, Ravichandran S. Clinically relevant reductions in HbA1c without hypoglycaemia: results across four studies of saxagliptin. Int J Clin Pract. 2013 Aug;67(8):759-67. doi: 10.1111/ijcp.12212. Epub 2013 Jun 24.
• Karyekar C, Donovan M, Allen E, Fleming D, Ravichandran S, Chen R. Efficacy and safety of saxagliptin combination therapy in US patients with type 2 diabetes. Postgrad Med. 2011 Jul;123(4):63-70. doi: 10.3810/pgm.2011.07.2305.
• Chacra AR, Tan GH, Ravichandran S, List J, Chen R; CV181040 Investigators. Safety and efficacy of saxagliptin in combination with submaximal sulphonylurea versus up-titrated sulphonylurea over 76 weeks. Diab Vasc Dis Res. 2011 Apr;8(2):150-9. doi: 10.1177/1479164111404574.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 17, 2009): 768
• Original Enrollment (submitted: April 11, 2006): 780
• Actual Study Completion Date: September 2008
• Actual Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Type 2 Diabetes.
• Treated with a sulfonylurea for at least 2 months.
• Inadequate blood sugar control.
• Are not on any other medications to lower blood sugar.
• No major heart, liver or kidney problems.
• Women not pregnant or breast feeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 77 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Hong Kong, Israel, Korea, Republic of, Mexico, Peru, Philippines, Puerto Rico, Singapore, South Africa, Taiwan, United States
• Removed Location Countries: Thailand

Administrative Information

• NCT Number: NCT00313313
• Other Study ID Numbers: CV181-040
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: AstraZeneca
• Original Responsible Party: Not Provided
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Bristol-Myers Squibb
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: AstraZeneca
• Verification Date: March 2015