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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00918138
First received: June 9, 2009
Last updated: June 4, 2014
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes
Drug: Saxagliptin
Drug: Metformin XR
Drug: Placebo matching Metformin XR
Drug: Placebo matching Saxagliptin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Change From Baseline in 24-Hour Mean Weighted Glucose (MWG) at Week 4 [ Time Frame: Baseline, Week 4 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline to Week 4 in 2-hour Postprandial Glucose (PPG) (2 Hours After the Evening Meal) [ Time Frame: Baseline, Week 4 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline Fasting Plasma Glucose (FPG) at Week 4, Obtained Immediately Before the Morning Meal [ Time Frame: Baseline, Week 4 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Participants With Confirmed Hypoglycemia Events During the Treatment Period [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
    'Confirmed' = recorded on the hypoglycemia AE case report form with a fingerstick for glucose <= 50 mg/dL and associated symptoms.

  • Participants With Reported Hypoglycemic Adverse Events During Treatment Period [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 219
Study Start Date: August 2009
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • BMS-477118
  • Onglyza
Drug: Metformin XR
Tablets, Oral, 1500 mg, once daily, 4 weeks
Other Name: Glucophage XR®
Drug: Placebo matching Metformin XR
Tablets, Oral, 0 mg, once daily, 4 weeks
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 Name: Glucophage XR®
Drug: Metformin XR
Tablets, Oral, 500 mg, once daily, 4 weeks
Other Name: Glucophage XR®
Drug: Placebo matching Saxagliptin
Tablets, Oral, 0 mg, once daily, 4 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 78 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00918138

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

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00918138     History of Changes
Other Study ID Numbers: CV181-085
Study First Received: June 9, 2009
Results First Received: September 2, 2011
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration
Israel: Ministry of Health
Mexico: Federal Commission for Sanitary Risks Protection
Mexico: Ethics Committee
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Saxagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014