Clinical trial NCT01606007: Safety and Efficacy of Combination Saxagliptin & Dapagliflozin Added to Metformin to Treat Subjects With Type 2 Diabetes
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-05-25
Enrollment: 1282
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24
timeFrame: Baseline (Week 0) and at Week 24
Secondary outcomes:
measure: 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])
timeFrame: Baseline (Week 0) and at Week 24
measure: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline (Week 0) and at Week 24
measure: Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: At Week 24
measure: Adjusted Mean Change From Baseline in Body Weight at Week 24
timeFrame: Baseline (Week 0) and at Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Alabama Research
state: Alabama
city: Homewood
country: United States
facility: Central Alabama Research
state: Alabama
city: Muscle Shoals
country: United States
facility: Terence T. Hart, Md
state: Alabama
city: Ozark
country: United States
facility: International Institute Of Clinical Research
state: Alabama
city: Mesa
country: United States
facility: Clinical Research Advantage
state: Arizona
city: Phoenix
country: United States
facility: Elite Clinical Studies, Llc
state: Arizona
city: Tucson
country: United States
facility: Genova Clinical Research
state: Arizona
city: Little Rock
country: United States
facility: Medical Investigations, Inc.
state: Arkansas
city: Little Rock
country: United States
facility: Aureus Research, Inc.
state: Arkansas
city: Fountain Valley
country: United States
facility: Southland Clinical Research Center, Inc.
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research
state: California
city: Los Angeles
country: United States
facility: National Research Inst
state: California
city: North Hollywood
country: United States
facility: Providence Clinical Research
state: California
city: Northridge
country: United States
facility: Diabetes Medical Center Of California
state: California
city: Northridge
country: United States
facility: Mehrdad Kevin Ariani Md, Inc.
state: California
city: Norwalk
country: United States
facility: Lucita M. Cruz,Md.,Inc.
state: California
city: Paramount
country: United States
facility: Center For Clinical Trials, Llc.
state: California
city: Sacramento
country: United States
facility: Center For Clinical Trials Of Sacramento, Inc.
state: California
city: San Jose
country: United States
facility: Trinitas Research, Inc
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Colorado Springs
country: United States
facility: Clinical Research Advantage
state: Colorado
city: Denver
country: United States
facility: Infocus Clinical Research
state: Colorado
city: Denver
country: United States
facility: Lynn Institute Of Denver
state: Colorado
city: Chiefland
country: United States
facility: Southeast Clinical Research, Llc
state: Florida
city: Coral Gables
country: United States
facility: Clinical Therapeutics Corporation
state: Florida
city: Jacksonville
country: United States
facility: Southeast Clinical Research, Llc
state: Florida
city: Kissimmee
country: United States
facility: Fpa Clinical Research
state: Florida
city: Miami Beach
country: United States
facility: Newphase Clinical Trials, Inc.
state: Florida
city: Miami
country: United States
facility: Clinical Research Of Miami, Inc.
state: Florida
city: Miami
country: United States
facility: Advanced Pharma Cr, Llc
state: Florida
city: Orlando
country: United States
facility: Omega Research Consultants, Llc
state: Florida
city: Palm Harbor
country: United States
facility: Palm Harbor Medical Associates
state: Florida
city: Pembroke Pines
country: United States
facility: Andres Patron, Do Pa
state: Florida
city: Roswell
country: United States
facility: Endocrine Research Solutions, Inc.
state: Georgia
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Vernon Hills
country: United States
facility: Deerbrook Medical Associates
state: Illinois
city: Council Bluffs
country: United States
facility: Clinical Research Advantage
state: Iowa
city: Eunice
country: United States
facility: Horizon Research Group Of Opelousas, Llc
state: Louisiana
city: Battle Creek
country: United States
facility: Associated Internal Medicine Specialists
state: Michigan
city: Detroit
country: United States
facility: Harris And Associates, P.C.
state: Michigan
city: Florissant
country: United States
facility: Patterson Medical Clinic
state: Missouri
city: Bellevue
country: United States
facility: Bellevue Family Practice
state: Nebraska
city: Elkhorn
country: United States
facility: Clinical Research Advantage
state: Nebraska
city: Fremont
country: United States
facility: Clinical Research Advantage
state: Nebraska
city: Omaha
country: United States
facility: Clinical Research Advantage
state: Nebraska
city: Blackwood
country: United States
facility: South Jersey Medical Associates, P.A.
state: New Jersey
city: Elizabeth
country: United States
facility: Central Jersey Health And Medical Research
state: New Jersey
city: West Seneca
country: United States
facility: Southgate Medical Group
state: New York
city: Charlotte
country: United States
facility: Metrolina Internal Medicine
state: North Carolina
city: Greensboro
country: United States
facility: Triad Clinical Trials, Llc
state: North Carolina
city: Morehead City
country: United States
facility: Diabetes & Endocrinology Consultants
state: North Carolina
city: Winston-salem
country: United States
facility: Pmg Research Of Winston-Salem, Llc
state: North Carolina
city: Akron
country: United States
facility: Daystar Clinical Resarch, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Sterling Research Grp, Ltd.
state: Ohio
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc.
state: Ohio
city: Dayton
country: United States
facility: Primed Clinical Research
state: Ohio
city: Zanesville
country: United States
facility: Physicians Research, Inc.
state: Ohio
city: Norman
country: United States
facility: Lynn Institute Of Norman
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Clinical Studies
state: Oregon
city: Portland
country: United States
facility: Oregon Clinical Research
state: Oregon
city: Beaver
country: United States
facility: Heritage Valley Medical Group
state: Pennsylvania
city: Shippensburg
country: United States
facility: Wellmon Family Practice
state: Pennsylvania
city: Columbia
country: United States
facility: Tlm Medical Services
state: South Carolina
city: Fountain Inn
country: United States
facility: Palmetto Clinical Trial Services Llc
state: South Carolina
city: Bristol
country: United States
facility: Holston Medical Group
state: Tennessee
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Knoxville
country: United States
facility: Pmg Research Of Knoxville
state: Tennessee
city: Arlington
country: United States
facility: Arlington Family Research Center, Inc.
state: Texas
city: Corpus Christi
country: United States
facility: Padre Coast Clinical Research
state: Texas
city: Dallas
country: United States
facility: Dallas Diabetes & Endocrine Center
state: Texas
city: Houston
country: United States
facility: Excel Clinical Research, Llc
state: Texas
city: North Richland Hills
country: United States
facility: North Hills Medical Research, Inc.
state: Texas
city: Pasadena
country: United States
facility: Med-Olam Clinical Research
state: Texas
city: San Antoinio
country: United States
facility: Sam Clinical Research Center
state: Texas
city: San Antonio
country: United States
facility: Covenant Clinical Research, Pa
state: Texas
city: Waco
country: United States
facility: Hillcrest Family Health Center
state: Texas
city: Bountiful
country: United States
facility: Val R. Hansen, M.D.
state: Utah
city: Salt Lake City
country: United States
facility: Highland Clinical Research
state: Utah
city: Bennington
country: United States
facility: Southwestern Vermont Med Cntr
state: Vermont
city: Suffolk
country: United States
facility: Hampton Roads Center For Clinical Research, Inc.
state: Virginia
city: Coquitlam
country: Canada
facility: Local Institution
state: British Columbia
city: Winnipeg
country: Canada
facility: Local Institution
state: Manitoba
city: Brampton
country: Canada
facility: Local Institution
state: Ontario
city: Smiths Falls
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Granby
country: Canada
facility: Local Institution
state: Quebec
city: Saskatoon
country: Canada
facility: Local Institution
state: Saskatchewan
city: Quebec
country: Canada
facility: Local Institution
city: Bucheon
country: Korea, Republic of
facility: Local Institution
state: Gyeonggi-do
city: Sungnam-si
country: Korea, Republic of
facility: Local Institution
state: Gyeonggi-do
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Incheon
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Cuautla
country: Mexico
facility: Local Institution
state: Morelos
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Merida
country: Mexico
facility: Local Institution
state: Yucatan
city: Aguascalientes
country: Mexico
facility: Local Institution
city: Chihuahua
country: Mexico
facility: Local Institution
city: Durango
country: Mexico
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution
city: Katowice
country: Poland
facility: Local Institution
city: Katowice
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Opole
country: Poland
facility: Local Institution
city: Poznan
country: Poland
facility: Local Institution
city: Pulawy
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Cidra
country: Puerto Rico
facility: Local Institution
city: Manati
country: Puerto Rico
facility: Local Institution
city: Ponce
country: Puerto Rico
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Local Institution
city: Villa Fontana
country: Puerto Rico
facility: Local Institution
city: Ploiesti
country: Romania
facility: Local Institution
state: Prahova
city: Ploiesti
country: Romania
facility: Local Institution
state: Prahova
city: Timisoara
country: Romania
facility: Local Institution
state: Timis
city: Bucharest
country: Romania
facility: Local Institution
city: Bucuresti
country: Romania
facility: Local Institution
city: Bucuresti
country: Romania
facility: Local Institution
city: Bucuresti
country: Romania
facility: Local Institution
city: Cluj Napoca Cluj
country: Romania
facility: Local Institution
city: Craiova
country: Romania
facility: Local Institution
city: Galati
country: Romania
facility: Local Institution
city: Soweto
country: South Africa
facility: Local Institution
state: Gauteng
city: Gauteng
country: South Africa
facility: Local Institution
state: Johannesburg
city: Durban
country: South Africa
facility: Local Institution
state: Kwa-Zulu Natal
city: Cape Town
country: South Africa
facility: Local Institution
state: Western Cape
city: Goodwood
country: South Africa
facility: Local Institution
state: Western Cape
city: Paarl
country: South Africa
facility: Local Institution
state: Western Cape
city: Rondebosch
country: South Africa
facility: Local Institution
state: Western Cape
city: Somerset West
country: South Africa
facility: Local Institution
state: Western Cape
city: Johannesburg
country: South Africa
facility: Local Institution
city: Johannesburg
country: South Africa
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.