An Efficacy & Safety Study of BMS-512148 in Combination With Metformin Extended Release Tablets

A Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Combination With Metformin as Initial Therapy as Compared With Dapagliflozin Monotherapy and Metformin Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control

The purpose of this clinical research study is to learn if initiating treatment with BMS-51248 (Dapagliflozin) in combination with metformin XR can improve diabetes control in patients with Type 2 Diabetes who do not receive any pharmacological treatment for diabetes, when compared to initial treatment with monotherapy dapagliflozin or metformin XR. The safety of this treatment will also be studied

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Metformin XR

• Study Type: Interventional
• Enrollment (Actual): 994
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Bucheon, Korea, Republic of, 420-717
    • Local Institution
  • Incheon, Korea, Republic of, 400-711
    • Local Institution
  • Incheon, Korea, Republic of, 105-760
    • Local Institution
  • Seoul, Korea, Republic of, 137-040
    • Local Institution
  • Sungnam-Si, Gyeonggi-Do, Korea, Republic of, 463-070
    • Local Institution
  • Gyeonggi-Do
    • Guri-Si, Gyeonggi-Do, Korea, Republic of, 471-701
      • Local Institution
  • Nowon-Gu
    • Seoul, Nowon-Gu, Korea, Republic of, 471-701
      • Local Institution
• Mexico
  • Aguascalientes, Mexico, 20127
    • Local Institution
  • Durango, Mexico, 34000
    • Local Institution
  • Veracruz, Mexico, 91910
    • Local Institution
  • Distrito Federal
    • Ciudad De Mexico, Distrito Federal, Mexico, 14000
      • Local Institution
  • Hidelgo
    • Pachuca, Hidelgo, Mexico, 42090
      • Local Institution
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44650
      • Local Institution
    • Guadalajara, Jalisco, Mexico, 44670
      • Local Institution
    • Guadalajara, Jalisco, Mexico, 44100
      • Local Institution
  • Michioacan
    • Morelia, Michioacan, Mexico, 58070
      • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64000
      • Local Institution
    • Monterrey, Nl, Nuevo Leon, Mexico, 64400
      • Local Institution
  • Tamaulipas
    • Tampico, Tamaulipas, Mexico, 89000
      • Local Institution
  • Yucatan
    • Merida, Yucatan, Mexico, 97070
      • Local Institution
• Philippines
  • Cebu City, Philippines, 6000
    • Local Institution
  • Jaro Iloilo City, Philippines, 5000
    • Local Institution
  • Las Pinas City, Philippines, 1740
    • Local Institution
  • Marikina City, Philippines, 1800
    • Local Institution
  • Pasig City, Philippines, 1600
    • Local Institution
  • Quezon City, Philippines, 1100
    • Local Institution
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Local Institution
  • Ponce, Puerto Rico, 00717
    • Local Institution
  • San Juan, Puerto Rico, 00920
    • Local Institution
  • San Juan, Puerto Rico, 00926
    • Local Institution
  • Villa Fontana, Puerto Rico, 00983
    • Local Institution
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Local Institution
  • Dzerzhinskiy, Russian Federation, 140091
    • Local Institution
  • Kemerovo, Russian Federation, 650066
    • Local Institution
  • Moscov, Russian Federation, 119048
    • Local Institution
  • Moscow, Russian Federation, 125299
    • Local Institution
  • Nizhniy Novgorod, Russian Federation, 603018
    • Local Institution
  • Novosibirsk, Russian Federation, 630091
    • Local Institution
  • Novosibirsk, Russian Federation, 630117
    • Local Institution
  • Saint-Petersburg, Russian Federation, 190068
    • Local Institution
  • Saratov, Russian Federation, 410028
    • Local Institution
  • St. Petersburg, Russian Federation, 191015
    • Local Institution
  • Volgograd, Russian Federation, 400001
    • Local Institution
  • Voronezh, Russian Federation, 394018
    • Local Institution
  • Yaroslav, Russian Federation, 150003
    • Local Institution
• Ukraine
  • Dnepropetrovsk, Ukraine, 49023
    • Local Institution
  • Donetsk, Ukraine, 83003
    • Local Institution
  • Kiev, Ukraine, 04050
    • Local Institution
  • Kiev, Ukraine, 4114
    • Local Institution
  • Lviv, Ukraine, 79010
    • Local Institution
  • Odessa, Ukraine, 65009
    • Local Institution
  • Odessa, Ukraine, 65039
    • Local Institution
  • Odessa, Ukraine, 65114
    • Local Institution
  • Vinnytsya, Ukraine, 21010
    • Local Institution
  • Zhytomyr, Ukraine, 10003
    • Local Institution
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35242
      • Greystone Medical Research, LLC
    • Haleyville, Alabama, United States, 35565
      • Winston Technology Research, LLC
  • Arizona
    • Tempe, Arizona, United States, 85282
      • Clinical Research Advantage, Inc.
  • California
    • Concord, California, United States, 94520
      • John Muir Physician Network Clinical Research Center
    • Fountain Valley, California, United States, 92708
      • Southland Clinical Research Center, Inc.
    • Fresno, California, United States, 93720
      • Valley Research
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Central Florida Clinical Trials, Inc.
    • Coral Gables, Florida, United States, 33134
      • Clinical Therapeutics Corporation
    • Gainesville, Florida, United States, 32605
      • Florida Research Network, LLC
    • Kissimmee, Florida, United States, 34741
      • FPA Clinical Research
    • Miami, Florida, United States, 33145
      • NextPhase Clinical Trials, Inc.
  • Georgia
    • Perry, Georgia, United States, 31069
      • Middle Georgia Drug Study Center, Llc
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center
    • Vernon Hills, Illinois, United States, 60061
      • Deerbrook Medical Associates
  • Mississippi
    • Rolling Fork, Mississippi, United States, 39159
      • Jackson Clinic
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Mercy Medical Group/Dba Woodlake Research
  • New York
    • Kingston, New York, United States, 12401
      • Hudson Valley Clinical Research Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • Metrolina Medical Research
    • Salisbury, North Carolina, United States, 28144
      • Crescent Medical Research
  • Ohio
    • Canal Fulton, Ohio, United States, 44614
      • Community Health Care, Inc.
    • Kettering, Ohio, United States, 45429
      • Wells Institute for Health Awareness
    • Newark, Ohio, United States, 43055
      • Newark Physician Associates
    • Zanesville, Ohio, United States, 43701
      • Physician Research, Inc.
  • Oklahoma
    • Bethany, Oklahoma, United States, 73008
      • Gilbert Medical Research, Llc
    • Oklahoma City, Oklahoma, United States, 73159
      • Integris Family Care South Penn
    • Yukon, Oklahoma, United States, 73099
      • Integris Family Care Yukon
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Willamette Valley Clinical Studies
  • Pennsylvania
    • Fleetwood, Pennsylvania, United States, 19522
      • Commonwealth Primary Care, Pc / Fleetwood Clinical Research
    • Shippensburg, Pennsylvania, United States, 17257
      • Biomedical Research Associates, Llc
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Safe Harbor Clinical Research
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Southeastern Research Associates, Inc.
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Tennessee
    • Fayetteville, Tennessee, United States, 37334
      • Middle Tennessee Clinical Research
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
  • Texas
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development
    • Houston, Texas, United States, 77004
      • Endocrine Associates
    • Houston, Texas, United States, 77024
      • Village Family Practice
    • Houston, Texas, United States, 77074
      • Non-Invasive Cardiovascular, Pa
    • Houston, Texas, United States, 77081
      • Excel Clinical Research, LLC
    • Midland, Texas, United States, 79705
      • Inst. Of Clin. Research At The Diabetes Cntr. Of The Sw
    • New Braunfels, Texas, United States, 78130
      • Hill Country Medical Associates
    • Pearland, Texas, United States, 77584
      • Southwest Clinical Research Center, Llc
    • San Antonio, Texas, United States, 78229
      • S.A.M. Clinical Research Center
    • San Antonio, Texas, United States, 78229
      • Covenant Clinical Research, Pa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males & females, 18-77 years old inclusive, with type 2 diabetes and with inadequate glycemic control
• Drug naive or treated with anti-diabetic medication for < 24 weeks since original diagnosis
• C-peptide ≥ 1.0 ng/mL
• Body Mass Index ≤ 45.0 kg/m
• Serum creatinine < 1.50 mg/dL for men or < 1.40 mg/dL for women

Exclusion Criteria:

• AST and/or ALT >3.0 times the upper limit of normal (ULN)
• Serum total bilirubin > 2.0 mg/dL
• Creatine kinase > 3X the upper limit of normal (ULN)
• Symptoms of severely uncontrolled diabetes
• Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric or rheumatic diseases

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Dapagliflozin (5 mg) + Metformin XR (up to 2000 mg)	Drug: Dapagliflozin; Tablets, Oral, Once daily, 24 weeks; Other Names: BMS-512148; Drug: Metformin XR; Tablets, Oral, Once daily, 24 weeks
Experimental: Arm 2; Dapagliflozin (5 mg)	Drug: Dapagliflozin; Tablets, Oral, Once daily, 24 weeks; Other Names: BMS-512148
Active Comparator: Arm 3; Metformin XR (500 mg up to 2000 mg)	Drug: Metformin XR; Tablets, Oral, Once daily, 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF])	HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the double- blind period.	From Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 in the double-blind period.	From Baseline to Week 24
Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. Mean and standard error for percentage of participants estimated by modified logistic regression model.	From Baseline to Week 24
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) in Subjects With Baseline HbA1c ≥ 9% at Week 24 (Last Observation Carried Forward [LOCF])	HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the double-blind period.	From Baseline to Week 24
Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period.	From Baseline to Week 24
Adjusted Mean Change From Baseline in Total Body Weight (kg) in Subjects With Baseline Body Mass Index (BMI) ≥ 27 kg/m^2 at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period.	From Baseline to Week 24

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Kohan DE, Fioretto P, Johnsson K, Parikh S, Ptaszynska A, Ying L. The effect of dapagliflozin on renal function in patients with type 2 diabetes. J Nephrol. 2016 Jun;29(3):391-400. doi: 10.1007/s40620-016-0261-1. Epub 2016 Feb 19.
• Henry RR, Murray AV, Marmolejo MH, Hennicken D, Ptaszynska A, List JF. Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial. Int J Clin Pract. 2012 May;66(5):446-56. doi: 10.1111/j.1742-1241.2012.02911.x. Epub 2012 Mar 13.

Helpful Links

• Publication

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: March 20, 2008
• First Submitted That Met QC Criteria: March 20, 2008
• First Posted (Estimate): March 26, 2008

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 27, 2023
• Last Verified: January 1, 2023

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; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Metformin
• Other Study ID Numbers: MB102-021