Safety and Efficacy of Combination Saxagliptin & Dapagliflozin Added to Metformin to Treat Subjects With Type 2 Diabetes

A Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Add-On Therapy With Saxagliptin and Dapagliflozin Added to Metformin Compared to Add-On Therapy With Saxagliptin in Combination With Metformin or Dapagliflozin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone.

The purpose of this study is to learn if a combination of BMS-477118 (Saxagliptin) and BMS -512148 (Dapagliflozin) added to Metformin can improve (decrease) Glycosylated Hemoglobin (Hemoglobin A1c) in patients with type 2 diabetes after 24 weeks of treatment. The safety of this treatment will also be studied.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 1282
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1N 4V3
    • Local Institution
  • British Columbia
    • Coquitlam, British Columbia, Canada, V3K 3V9
      • Local Institution
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E3P4
      • Local Institution
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Local Institution
    • Smiths Falls, Ontario, Canada, K7A 4W8
      • Local Institution
    • Toronto, Ontario, Canada, M9W 4L6
      • Local Institution
  • Quebec
    • Granby, Quebec, Canada, J2G 8Z9
      • Local Institution
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 3H3
      • Local Institution
• Korea, Republic of
  • Daegu, Korea, Republic of, 700-721
    • Local Institution
  • Incheon, Korea, Republic of, 405-760
    • Local Institution
  • Seoul, Korea, Republic of, 120-752
    • Local Institution
  • Seoul, Korea, Republic of, 137-701
    • Local Institution
  • Seoul, Korea, Republic of, 110-774
    • Local Institution
  • Gyeonggi-do
    • Bucheon, Gyeonggi-do, Korea, Republic of, 420-717
      • Local Institution
    • Sungnam-si, Gyeonggi-do, Korea, Republic of, 463-712
      • Local Institution
• Mexico
  • Aguascalientes, Mexico, 20230
    • Local Institution
  • Chihuahua, Mexico, 31217
    • Local Institution
  • Durango, Mexico, 34000
    • Local Institution
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44670
      • Local Institution
  • Morelos
    • Cuautla, Morelos, Mexico, 62744
      • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64710
      • Local Institution
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Local Institution
  • Yucatan
    • Merida, Yucatan, Mexico, 97070
      • Local Institution
• Poland
  • Gdansk, Poland, 80-546
    • Local Institution
  • Katowice, Poland, 40-057
    • Local Institution
  • Katowice, Poland, 40954
    • Local Institution
  • Krakow, Poland, 30-015
    • Local Institution
  • Lodz, Poland, 90-242
    • Local Institution
  • Opole, Poland, 45-367
    • Local Institution
  • Poznan, Poland, 61-655
    • Local Institution
  • Pulawy, Poland, 24-100
    • Local Institution
  • Warszawa, Poland, 03-580
    • Local Institution
• Puerto Rico
  • Cidra, Puerto Rico, 00739
    • Local Institution
  • Manati, Puerto Rico, 00674
    • Local Institution
  • Ponce, Puerto Rico, 00716
    • Local Institution
  • San Juan, Puerto Rico, 00909
    • Local Institution
  • San Juan, Puerto Rico, 00926
    • Local Institution
  • San Juan, Puerto Rico, 00935
    • Local Institution
  • Villa Fontana, Puerto Rico, 00983
    • Local Institution
• Romania
  • Bucharest, Romania, 050538
    • Local Institution
  • Bucuresti, Romania, 020359
    • Local Institution
  • Bucuresti, Romania, 020475
    • Local Institution
  • Bucuresti, Romania, 11794
    • Local Institution
  • Cluj Napoca Cluj, Romania, 400006
    • Local Institution
  • Craiova, Romania, 200349
    • Local Institution
  • Galati, Romania, 800098
    • Local Institution
  • Prahova
    • Ploiesti, Prahova, Romania, 100018
      • Local Institution
    • Ploiesti, Prahova, Romania, 100163
      • Local Institution
  • Timis
    • Timisoara, Timis, Romania, 300736
      • Local Institution
• South Africa
  • Johannesburg, South Africa, 1829
    • Local Institution
  • Johannesburg, South Africa, 2129
    • Local Institution
  • Gauteng
    • Soweto, Gauteng, South Africa, 2013
      • Local Institution
  • Johannesburg
    • Gauteng, Johannesburg, South Africa, 1818
      • Local Institution
  • Kwa-Zulu Natal
    • Durban, Kwa-Zulu Natal, South Africa, 4001
      • Local Institution
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7500
      • Local Institution
    • Goodwood, Western Cape, South Africa, 7460
      • Local Institution
    • Paarl, Western Cape, South Africa, 7646
      • Local Institution
    • Rondebosch, Western Cape, South Africa, 7700
      • Local Institution
    • Somerset West, Western Cape, South Africa, 7130
      • Local Institution
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Central Alabama Research
    • Homewood, Alabama, United States, 35244
      • Central Alabama Research
    • Muscle Shoals, Alabama, United States, 35662
      • Terence T. Hart, MD
    • Ozark, Alabama, United States, 36360
      • International Institute Of Clinical Research
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Clinical Research Advantage
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies, LLC
    • Tucson, Arizona, United States, 85704
      • Genova Clinical Research
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Medical Investigations, Inc.
    • Little Rock, Arkansas, United States, 72211
      • Aureus Research, Inc.
  • California
    • Fountain Valley, California, United States, 92708
      • Southland Clinical Research Center, Inc.
    • Lomita, California, United States, 90717
      • Torrance Clinical Research
    • Los Angeles, California, United States, 90057
      • National Research Inst
    • North Hollywood, California, United States, 91606
      • Providence Clinical Research
    • Northridge, California, United States, 91325
      • Diabetes Medical Center Of California
    • Northridge, California, United States, 91325
      • Mehrdad Kevin Ariani Md, Inc.
    • Norwalk, California, United States, 90650
      • Lucita M. Cruz,Md.,Inc.
    • Paramount, California, United States, 90723
      • Center for Clinical Trials, LLC.
    • Sacramento, California, United States, 95823
      • Center for Clinical Trials of Sacramento, Inc.
    • San Jose, California, United States, 95116
      • Trinitas Research, Inc
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80906
      • Clinical Research Advantage
    • Denver, Colorado, United States, 80246
      • Lynn Institute of Denver
    • Denver, Colorado, United States, 80211
      • InFocus Clinical Research
  • Florida
    • Chiefland, Florida, United States, 32626
      • Southeast Clinical Research, LLC
    • Coral Gables, Florida, United States, 33134
      • Clinical Therapeutics Corporation
    • Jacksonville, Florida, United States, 32216
      • Southeast Clinical Research, LLC
    • Kissimmee, Florida, United States, 34741
      • FPA Clinical Research
    • Miami, Florida, United States, 33136
      • Advanced Pharma CR, LLC
    • Miami, Florida, United States, 33126
      • Clinical Research Of Miami, Inc.
    • Miami Beach, Florida, United States, 33140
      • Newphase Clinical Trials, Inc.
    • Orlando, Florida, United States, 32804
      • Omega Research Consultants, LLC
    • Palm Harbor, Florida, United States, 34684
      • Palm Harbor Medical Associates
    • Pembroke Pines, Florida, United States, 33026
      • Andres Patron, DO PA
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Endocrine Research Solutions, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60607-4559
      • Cedar Crosse Research Center
    • Vernon Hills, Illinois, United States, 60061
      • Deerbrook Medical Associates
  • Iowa
    • Council Bluffs, Iowa, United States, 51503
      • Clinical Research Advantage
  • Louisiana
    • Eunice, Louisiana, United States, 70535
      • Horizon Research Group of Opelousas, LLC
  • Michigan
    • Battle Creek, Michigan, United States, 49015
      • Associated Internal Medicine Specialists
    • Detroit, Michigan, United States, 48235
      • Harris And Associates, P.C.
  • Missouri
    • Florissant, Missouri, United States, 63031
      • Patterson Medical Clinic
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • Bellevue Family Practice
    • Elkhorn, Nebraska, United States, 68022
      • Clinical Research Advantage
    • Fremont, Nebraska, United States, 68025
      • Clinical Research Advantage
    • Omaha, Nebraska, United States, 68130
      • Clinical Research Advantage
  • New Jersey
    • Blackwood, New Jersey, United States, 08012
      • South Jersey Medical Associates, P.A.
    • Elizabeth, New Jersey, United States, 07205
      • Central Jersey Health And Medical Research
  • New York
    • West Seneca, New York, United States, 14224
      • Southgate Medical Group
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Metrolina Internal Medicine
    • Greensboro, North Carolina, United States, 27410
      • Triad Clinical Trials, LLC
    • Morehead City, North Carolina, United States, 28557
      • Diabetes & Endocrinology Consultants
    • Winston-salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem, LLC
  • Ohio
    • Akron, Ohio, United States, 44313
      • Daystar Clinical Resarch, Inc.
    • Cincinnati, Ohio, United States, 45246
      • Sterling Research Grp, Ltd.
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research, Inc.
    • Dayton, Ohio, United States, 45419
      • PriMED Clinical Research
    • Zanesville, Ohio, United States, 43701
      • Physicians Research, Inc.
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Lynn Institute of Norman
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Willamette Valley Clinical Studies
    • Portland, Oregon, United States, 97220
      • Oregon Clinical Research
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Heritage Valley Medical Group
    • Shippensburg, Pennsylvania, United States, 17257
      • Wellmon Family Practice
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • TLM Medical Services
    • Fountain Inn, South Carolina, United States, 29644
      • Palmetto Clinical Trial Services LLC
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Holston Medical Group
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
    • Knoxville, Tennessee, United States, 37912
      • PMG Research of Knoxville
  • Texas
    • Arlington, Texas, United States, 76012
      • Arlington Family Research Center, Inc.
    • Corpus Christi, Texas, United States, 78404
      • Padre Coast Clinical Research
    • Dallas, Texas, United States, 75230-2548
      • Dallas Diabetes & Endocrine Center
    • Houston, Texas, United States, 77035
      • Excel Clinical Research, LLC
    • North Richland Hills, Texas, United States, 76180
      • North Hills Medical Research, Inc.
    • Pasadena, Texas, United States, 77504
      • Med-Olam Clinical Research
    • San Antoinio, Texas, United States, 78229
      • Sam Clinical Research Center
    • San Antonio, Texas, United States, 78229
      • Covenant Clinical Research, Pa
    • Waco, Texas, United States, 76710
      • Hillcrest Family Health Center
  • Utah
    • Bountiful, Utah, United States, 84010
      • Val R. Hansen, M.D.
    • Salt Lake City, Utah, United States, 84124
      • Highland Clinical Research
  • Vermont
    • Bennington, Vermont, United States, 05201
      • Southwestern Vermont Med Cntr
  • Virginia
    • Suffolk, Virginia, United States, 23435
      • Hampton Roads Center for Clinical Research, Inc.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subjects with Type 2 diabetes mellitus (T2DM) with HbA1c ≥ 8.0% and ≤ 12.0%
• Stable metformin therapy dose of ≥ 1500mg for at least 8 weeks prior to screening
• Body mass index (BMI) ≤ 45.0kg/m2

Exclusion Criteria:

• Estimated glomerular filtration rate (eGFR) < 60mL/min/1,73m2 and Serum Creatinine (Scr) ≥ 1.5 mg/dL in males or ≥ 1.4 mg/dL in females
• Uncontrolled hypertension Systolic Blood Pressure (SBP) ≥ 160mmHg and/or Diastolic Blood Pressure (DBP) ≥ 100mmHg
• Hepatic disease
• Cardiovascular disease within 3 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1: Saxagliptin+Metformin XR+Placebo	Drug: Saxagliptin; Tablets, Oral, 5mg , Once daily, 24 weeks; Other Names: Onglyza; Drug: Metformin XR; Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks; Other Names: Glucophage XR; Drug: Placebo matching with Dapagliflozin; Tablets, Oral, 0mg, Once daily, 24 weeks
Active Comparator: Arm 2: Dapagliflozin+Metformin XR+Placebo	Drug: Metformin XR; Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks; Other Names: Glucophage XR; Drug: Dapagliflozin; Tablets, Oral, 10mg , Once daily, 24 weeks; Other Names: BMS-512148; Drug: Placebo matching with Saxagliptin; Tablets, Oral, 0mg, Once daily, 24 weeks
Experimental: Arm 3: Saxagliptin+Dapagliflozin+Metformin XR	Drug: Saxagliptin; Tablets, Oral, 5mg , Once daily, 24 weeks; Other Names: Onglyza; Drug: Metformin XR; Tablets, Oral, ≥ 1500mg/≤ 2000mg, Once daily, 24 weeks; Other Names: Glucophage XR; Drug: Dapagliflozin; Tablets, Oral, 10mg , Once daily, 24 weeks; Other Names: BMS-512148

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	HbA1c was measured as percent of hemoglobin by a central laboratory. 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 at Week 24 in the double-blind period, including observations prior to rescue.	Baseline (Week 0) and at Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline in 2-hour Post Prandial Glucose (PPG) From a Liquid Meal Tolerance Test (MTT) at Week 24 (Last Observation Carried Forward [LOCF])	Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. PPG measurements were obtained at week 24 in the doubleblind period, including observations prior to rescue.	Baseline (Week 0) and at Week 24
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	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 at Week 24 in the doubleblind period, including observations prior to rescue.	Baseline (Week 0) and at Week 24
Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])	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.	At Week 24
Adjusted Mean Change From Baseline in Body Weight at Week 24	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 at Week 24 in the doubleblind period, including observations prior to rescue.	Baseline (Week 0) and at Week 24

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Bailey CJ, Del Prato S, Wei C, Reyner D, Saraiva G. Durability of glycaemic control with dapagliflozin, an SGLT2 inhibitor, compared with saxagliptin, a DPP4 inhibitor, in patients with inadequately controlled type 2 diabetes. Diabetes Obes Metab. 2019 Nov;21(11):2564-2569. doi: 10.1111/dom.13841. Epub 2019 Aug 26.
• Rosenstock J, Hansen L, Zee P, Li Y, Cook W, Hirshberg B, Iqbal N. Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin. Diabetes Care. 2015 Mar;38(3):376-83. doi: 10.2337/dc14-1142. Epub 2014 Oct 28.
• Rosenstock J, Mathieu C, Chen H, Garcia-Sanchez R, Saraiva GL. Dapagliflozin versus saxagliptin as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin. Arch Endocrinol Metab. 2018 Aug;62(4):424-430. doi: 10.20945/2359-3997000000056.

Helpful Links

• BMS clinical trial educational resource
• CV_181169_Protocol_Redacted
• CV181169_Synopsis

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: May 23, 2012
• First Submitted That Met QC Criteria: May 24, 2012
• First Posted (Estimate): May 25, 2012

Study Record Updates

• Last Update Posted (Actual): May 15, 2017
• Last Update Submitted That Met QC Criteria: March 29, 2017
• Last Verified: March 1, 2017

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; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Dapagliflozin; Metformin; Saxagliptin
• Other Study ID Numbers: CV181-169; 2012-000679-18 (EudraCT Number)