A Study Assessing Saxagliptin Treatment in Type 2 Diabetic Subjects Who Are Not Controlled With TZD Therapy Alone

• ClinicalTrials.gov Identifier: NCT00295633
• Recruitment Status: Completed
• First Posted: February 24, 2006
• Results First Posted: September 25, 2009
• Last Update Posted: April 7, 2015
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: February 22, 2006
• First Posted Date: February 24, 2006
• Results First Submitted Date: August 17, 2009
• Results First Posted Date: September 25, 2009
• Last Update Posted Date: April 7, 2015
• Study Start Date: March 2006
• Actual Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 11, 2010)

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: February 22, 2006): Change in A1C level at Week 24

Current Secondary Outcome Measures (submitted: April 11, 2010)

• 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 Diabetic Association's defined goal for glycemia, at each dose of saxagliptin plus TZD versus placebo plus TZD 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 achieved at each dose of saxagliptin plus TZD versus placebo plus TZD at Week 24, adjusted for baseline value.

• Original Secondary Outcome Measures (submitted: February 22, 2006): Change from 0 to 180 minutes for postprandial glucose (PPG) response to an oral glucose tolerance test (OGTT); change in fasting plasma glucose (FPG); proportion of subjects achieving a therapeutic glycemic response (A1C <7.0%)
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Assessing Saxagliptin Treatment in Type 2 Diabetic Subjects Who Are Not Controlled With TZD Therapy Alone
• Official Title: A Multicenter, Randomized, Double Blind, Placebo Controlled, Phase III Trial to Evaluate the Efficacy and Safety of Saxagliptin (BMS477118) in Combination With Thiazolidinedione Therapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Thiazolidinedione Therapy Alone
• Brief Summary: The purpose of this clinical research study is to learn whether Saxagliptin added to thiazolidinedione (TZD) therapy is more effective than TZD alone as a treatment for Type 2 diabetic subjects who are not sufficiently controlled with TZD alone
• 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 will be eligible to enter the long-term treatment extension period where they will receive metformin (defined as rescue medication) added onto their blinded study medication
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Diabetes Mellitus, Type 2

Intervention

• Drug: Saxagliptin
  Tablets, Oral, 2.5 mg, Once daily (6 months ST, 12 months LT)
  Other Name: BMS-477118
• Drug: Saxagliptin
  Tablets, Oral, 5 mg, once daily (6 months ST, 12 months LT)
  Other Name: BMS-477118
• Drug: Placebo
  Tablets, Oral, 0 mg, Once daily (6 months ST, 12 months LT)
• Drug: pioglitazone
  Tablets, Oral, 30 mg or 45 mg, once daily (6 months ST, 12 months LT)
• Drug: rosiglitazone
  Tablets, Oral, 4 mg, once daily or 8 mg, either as once or twice daily (6 months ST, 12 months LT)
• Drug: metformin
  Tablets, Oral, 500-2500 mg, as needed (12 months LT)

Study Arms

• Experimental: Saxagliptin plus open-label TZD (A)

  Saxagliptin PLUS pioglitazone OR rosiglitazone

  PLUS open-label metformin (as needed as rescue medication)

  Interventions:

  • Drug: Saxagliptin
  • Drug: pioglitazone
  • Drug: rosiglitazone
  • Drug: metformin
• Experimental: Saxagliptin plus open-label TZD (B)

  Saxagliptin PLUS pioglitazone OR rosiglitazone

  PLUS open-label metformin (as needed as rescue medication)

  Interventions:

  • Drug: Saxagliptin
  • Drug: pioglitazone
  • Drug: rosiglitazone
  • Drug: metformin
• Placebo Comparator: Placebo plus open-label TZD (C)

  Placebo PLUS pioglitazone OR rosiglitazone

  PLUS open-label metformin (as needed as rescue medication)

  Interventions:

  • Drug: Placebo
  • Drug: pioglitazone
  • Drug: rosiglitazone
  • Drug: metformin

Publications *

• Hollander P, Li J, Allen E, Chen R; CV181-013 Investigators. Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone. J Clin Endocrinol Metab. 2009 Dec;94(12):4810-9. doi: 10.1210/jc.2009-0550. Epub 2009 Oct 28.
• 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.
• Hollander PL, Li J, Frederich R, Allen E, Chen R; CV181013 Investigators. Safety and efficacy of saxagliptin added to thiazolidinedione over 76 weeks in patients with type 2 diabetes mellitus. Diab Vasc Dis Res. 2011 Apr;8(2):125-35. doi: 10.1177/1479164111404575.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 19, 2009): 565
• Original Enrollment (submitted: February 22, 2006): 555
• Actual Study Completion Date: October 2008
• Actual Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Type 2 diabetics currently receiving a stable dose of TZD monotherapy (pioglitazone 30mg or 45mg, or rosiglitazone 4mg or 8mg) for at least 12 weeks prior to screening.
• Hemoglobin A1c (HbA1c) > = 7.0% and < = 10.5%
• Body mass index < = 45kg/m2
• Fasting C-peptide > = 1 ng/mL

Exclusion Criteria:

• Symptomatic poorly controlled diabetes
• Recent cardiac or cerebrovascular event
• Serum creatinine > = 2.0 mg/dL

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, Canada, India, Mexico, Peru, Philippines, Puerto Rico, United States

Administrative Information

• NCT Number: NCT00295633
• Other Study ID Numbers: CV181-013
• 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

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: AstraZeneca
• Verification Date: March 2015