52-week add-on to Metformin Comparison of Saxagliptin and Sulphonylurea, With a 52-week Extension Period

• ClinicalTrials.gov Identifier: NCT00575588
• Recruitment Status: Completed
• First Posted: December 18, 2007
• Results First Posted: September 6, 2010
• Last Update Posted: March 21, 2012
• Sponsor: AstraZeneca
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: December 14, 2007
• First Posted Date: December 18, 2007
• Results First Submitted Date: August 10, 2010
• Results First Posted Date: September 6, 2010
• Last Update Posted Date: March 21, 2012
• Study Start Date: December 2007
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 30, 2011)

Hemoglobin A1c (HbA1c) Change From Baseline to Week 52 [ Time Frame: Baseline to 52 Weeks ]

Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 52 (Per Protocol Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 52 value minus the baseline value.

• Original Primary Outcome Measures (submitted: December 14, 2007): Absolute change from baseline in glycosylated haemoglobin A1c (HbA1c)

Current Secondary Outcome Measures (submitted: June 30, 2011)

• Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 52 Weeks [ Time Frame: From Baseline to Week 52 ]
  Proportion of participants reporting at least one episode of any hypoglycaemic event for saxagliptin added on to metformin versus glipizide added on to metformin over 52 weeks (Safety Analysis Set)
• Body Weight Change From Baseline to Week 52 [ Time Frame: Baseline, Week 52 (Last Observation Carried Forward) ]
  Adjusted mean change from baseline in Body Weight achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 52 (Safety Analysis Set). Body Weight is a continuous measure, the change from baseline for each participant is calculated as the Week 52 (LOCF) value minus the baseline value.
• Mean Slope of the Regressions of Change From Week 24 to Week 52 in HbA1c [ Time Frame: Week 24 to Week 52 ]
  Mean slopes of regression of change from Week 24 to Week 52 in HbA1c for saxagliptin added on to metformin versus glipizide added on to metformin (Per Protocol Analysis Set) achieved by fitting a mixed model with subject specific slopes for the time effect (weeks on randomized treatment was utilized). This analysis gives an assessment of the durability of the HbA1c effect.

• Original Secondary Outcome Measures (submitted: December 14, 2007): Safety and tolerability Other secondary measurements of glucose metabolism

Current Other Pre-specified Outcome Measures (submitted: May 4, 2011)

• Hemoglobin A1c (HbA1c) Change From Baseline to Week 104 [ Time Frame: Baseline, Week 104 ]
  Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 104 (Full Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 104 value minus the baseline value.
• Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 104 Weeks [ Time Frame: Baseline, Week 104 ]
  Proportion of participants reporting at least one episode of any hypoglycaemic event for saxagliptin added on to metformin versus glipizide added on to metformin over 104 weeks (Safety Analysis Set)
• Body Weight Change From Baseline to Week 104 [ Time Frame: Baseline, Week 104 ]
  Adjusted mean change from baseline in Body Weight achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 104. Body Weight is a continuous measure, the change from baseline for each participant is calculated as the Week 104 value minus the baseline value.
• Mean Slope of the Regressions of Change From Week 24 to Week 104 in HbA1c [ Time Frame: Week 24 to Week 104 ]
  Mean slopes of regression of change from Week 24 to Week 104 in HbA1c for saxagliptin added on to metformin versus glipizide added on to metformin (Full Analysis Set) achieved by fitting a mixed model with subject specific slopes for the time effect (weeks on randomized treatment was utilized). This analysis gives an assessment of the durability of the HbA1c effect.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 52-week add-on to Metformin Comparison of Saxagliptin and Sulphonylurea, With a 52-week Extension Period
• Official Title: A 52-Week International, Multi-centre, Randomized, Parallel-group, Double-blind, Active-controlled, Phase III Study With a 52-Week Extension Period to Evaluate the Safety and Efficacy of Saxagliptin in Combination With Metformin Compared With Sulphonylurea in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Therapy Alone.
• Brief Summary: Saxagliptin is a new investigational medication being developed for treatment of type 2 diabetes. This study is designed to assess the efficacy and tolerability of saxagliptin in addition to metformin and compare to sulphonylurea in addition with metformin.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Type 2 Diabetes

Intervention

• Drug: Metformin
  open-label metformin
• Drug: Sulphonylurea
  Glipizide 5-20 mg capsules (titrated to optimal effect or highest tolerable dose during 18 weeks)
• Drug: Saxagliptin
  Saxagliptin 5 mg tablets
  Other Name: Onglyza

Study Arms

• Experimental: Saxagliptin
  Interventions:

  • Drug: Metformin
  • Drug: Saxagliptin
• Experimental: Glipizide
  Interventions:

  • Drug: Metformin
  • Drug: Sulphonylurea

Publications *

• Cook W, Minervini G, Bryzinski B, Hirshberg B. Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials. Postgrad Med. 2014 Oct;126(6):19-32. doi: 10.3810/pgm.2014.10.2818.
• Mintz ML, Minervini G. Saxagliptin versus glipizide as add-on therapy to metformin: assessment of hypoglycemia. Curr Med Res Opin. 2014 May;30(5):761-70. doi: 10.1185/03007995.2014.880674. Epub 2014 Jan 30.
• Göke B, Gallwitz B, Eriksson JG, Hellqvist Å, Gause-Nilsson I. Saxagliptin vs. glipizide as add-on therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: long-term (52-week) extension of a 52-week randomised controlled trial. Int J Clin Pract. 2013 Apr;67(4):307-16.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 10, 2010): 891
• Original Estimated Enrollment (submitted: December 14, 2007): 838
• Actual Study Completion Date: August 2010
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosed with type 2 diabetes,
• Treatment with metformin alone on stable doses of 1500 mg or higher per day for at least 8 weeks prior to Visit 1,
• HbA1c >6.5% and ≤10.0%

Exclusion Criteria:

• Type 1 diabetes,
• history of diabetic ketoacidosis or hyperosmolar non-ketonic coma,
• Insulin therapy within one year of enrolment (with the exception of insulin therapy during a hospitalization or use in gestational diabetes)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Finland, Germany, Hungary, India, Korea, Republic of, Netherlands, Norway, Russian Federation, Slovakia, United Kingdom, Vietnam

Administrative Information

• NCT Number: NCT00575588
• Other Study ID Numbers: D1680C00001; EudraCT number 2007-003998-55
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: AstraZeneca
• Study Sponsor: AstraZeneca
• Collaborators: Bristol-Myers Squibb

Investigators

• Principal Investigator: Burkhard Goke; University of Munich, Germany
• Study Director: Peter Ohman, MD; AstraZeneca
• Study Chair: Deborah Price, MSc; AstraZeneca

• PRS Account: AstraZeneca
• Verification Date: March 2012