Study To Evaluate 24 Hour Blood Sugar Control (24-hour Mean Weighted Glucose) In Subjects That Are Taking Saxagliptin 5 mg Added Onto Metformin XR 1500 XR mg Compared To Subjects Taking Metformin XR 1500 mg Up-titrated To Metformin XR 2000 mg

A 4-Week, Multicenter, Randomized, Double-Blind, Phase 3b Trial to Evaluate the Efficacy of Saxagliptin in Combination With Metformin XR 1500 mg Versus Up-titrated Metformin XR to 2000 mg in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise and a Stable Dose of Metformin XR 1500 mg

The purpose of this study was to compare effect of Saxagliptin as add-on to Metformin on 24-hour mean weighted glucose (MWG) to the effect of uptitrating Metformin in subjects with T2DM inadequately controlled on metformin alone.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Saxagliptin; Drug: Metformin XR; Drug: Placebo matching Metformin XR; Drug: Metformin XR; Drug: Placebo matching Saxagliptin

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1425
    • Local Institution
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1429
      • Local Institution
• Israel
  • Beer-Sheva, Israel, 84101
    • Local Institution
  • Holon, Israel, 58100
    • Local Institution
  • Kfar-Saba, Israel, 44281
    • Local Institution
  • Zefat, Israel, 13100
    • Local Institution
• Mexico
  • Durango, Mexico, 34000
    • Local Institution
  • Durango, Mexico, 34075
    • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Local Institution
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Dedicated Phase I, Inc.
  • California
    • Redlands, California, United States, 92373
      • Pacific Sleep Medicine Services (Avastra Clinical Trials)
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • Hialeah, Florida, United States, 33012
      • Palm Springs Research Institute
    • North Miami, Florida, United States, 33161
      • Healthcare Clinical Data, Inc.
  • Georgia
    • Blue Ridge, Georgia, United States, 30513
      • River Birch Research Alliance, LLC
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Jasper Clinic, Inc.
  • New York
    • New York, New York, United States, 10019
      • Clinilabs, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Medpace Clinical Pharmacology Unit
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas Inc.
  • Utah
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes
• 18-78 years of age
• Taking stable dose of metformin immediate release (IR) or XR ≥850 mg and ≤1500 mg as monotherapy for at least 8 weeks prior to screening
• Glycosylated hemoglobin A1C (A1C) 7.5-11.5% at screening
• Fasting C-peptide: ≥1.0 ng/mL
• FPG≥126 mg/dl obtained at the Day -7 visit
• Body mass index (BMI): ≤ 40kg/m²
• A1C ≥ 7.0% and ≤ 11.0% obtained at the Day -7 visit for randomization

Exclusion Criteria:

• Women of childbearing potential unable or unwilling to use acceptable birth control
• Women who are pregnant or breastfeeding
• Significant cardiovascular history
• Active liver disease
• Renal impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saxagliptin + Metformin XR + matching Metformin XR placebo; (Saxagliptin 5 mg plus Metformin XR 1500 plus matching Metformin XR 500 mg placebo)	Drug: Saxagliptin; Tablets, Oral, 5 mg, once daily, 4 weeks; Other Names: Onglyza; BMS-477118; Drug: Metformin XR; Tablets, Oral, 1500 mg, once daily, 4 weeks; Other Names: Glucophage XR®; Drug: Placebo matching Metformin XR; Tablets, Oral, 0 mg, once daily, 4 weeks; Drug: Metformin XR; Tablets, Oral, 500 mg, once daily, 4 weeks; Other Names: Glucophage XR®
Active Comparator: Metformin XR + Metformin XR + matching Saxagliptin placebo; (Metformin XR 500 mg plus Metformin XR 1500 mg plus matching Saxagliptin 5 mg placebo)	Drug: Metformin XR; Tablets, Oral, 1500 mg, once daily, 4 weeks; Other Names: Glucophage XR®; Drug: Metformin XR; Tablets, Oral, 500 mg, once daily, 4 weeks; Other Names: Glucophage XR®; Drug: Placebo matching Saxagliptin; Tablets, Oral, 0 mg, once daily, 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 24-Hour Mean Weighted Glucose (MWG) at Week 4	Adjusted mean change from baseline in MWG achieved with saxagliptin 5 mg plus metformin XR versus placebo plus metformin XR at Week 24. MWG was calculated as the area under the curve (AUC) for the full 24 hours expressed as average mg/dL. Glucose measurements were collected 30 minutes before and just prior to each meal (0 minutes) and 30, 60, 120, and 180 minutes after each meal (with 1 additional measurement at 240 minutes after the evening meal), midnight, 3 AM, and at end-of-domicile visit 24 hours after the first measurement. Mean change from baseline was adjusted for baseline value.	Baseline, Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 4 in 2-hour Postprandial Glucose (PPG) (2 Hours After the Evening Meal)	Adjusted mean change from baseline in 2-hour postprandial (after mealtime) plasma glucose two hours after start of the evening meal during 24-hour domicile visits evaluated both at pre-randomization (baseline) and at Week 4. Mean change from baseline was adjusted for baseline value.	Baseline, Week 4
Change From Baseline Fasting Plasma Glucose (FPG) at Week 4, Obtained Immediately Before the Morning Meal	FPG measurements were done at baseline, day 14 and 28. At baseline and day 28, the FPG value=plasma glucose value collected 30 minutes prior to the morning meal during the domicile visit.	Baseline, Week 4

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Confirmed Hypoglycemia Events During the Treatment Period	'Confirmed' = recorded on the hypoglycemia AE case report form with a fingerstick for glucose <= 50 mg/dL and associated symptoms.	AEs: up to last treatment day (LTD) +1 day or last visit day (LVD), whichever came last ; SAEs: up to LTD +30 days or LVD + 30 days, whichever came last. Mean duration of exposure=27.7 days for Saxa 5 mg + Met XR 1500 mg, and 28.3 days for Met 2000 mg.
Participants With Reported Hypoglycemic Adverse Events During Treatment Period	Hypoglycemic events are based upon the Saxagliptin Predefined List of Events, which includes hypoglycemia, blood glucose decreased, and hypoglycemic unconsciousness. The Hypoglycemic events occurred in less than 5% of the participants and hence do not appear in the adverse events module.	AEs: up to last treatment day (LTD) +1 day or last visit day (LVD), whichever came last ; SAEs: up to LTD +30 days or LVD + 30 days, whichever came last. Mean duration of exposure=27.7 days for Saxa 5 mg + Met XR 1500 mg, and 28.3 days for Met 2000 mg.

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: June 9, 2009
• First Submitted That Met QC Criteria: June 10, 2009
• First Posted (Estimate): June 11, 2009

Study Record Updates

• Last Update Posted (Estimate): May 21, 2015
• Last Update Submitted That Met QC Criteria: May 4, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Saxagliptin
• Other Study ID Numbers: CV181-085