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

Type 2 Diabetes Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01606007
• Other study ID #: CV181-169
• Secondary ID: 2012-000679-18
• Status: Completed
• Phase: Phase 3
• First received: May 23, 2012
• Last updated: December 22, 2015
• Start date: July 2012
• Est. completion date: January 2014

Study information

• Verified date: December 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug AdministrationCanada: Health CanadaMexico: Federal Commission for Protection Against Health RisksGermany: Federal Institute for Drugs and Medical DevicesBrazil: Ethics CommitteeBrazil: National Committee of Ethics in ResearchBrazil: National Health Surveillance AgencyArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaPoland: Ethics CommitteePoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRomania: Ethics CommitteeRomania: National Agency for Medicines and Medical DevicesSouth Korea: Institutional Review BoardSouth Korea: Korea Food and Drug Administration (KFDA)South Africa: Department of HealthSouth Africa: Human Research Ethics CommitteeSouth Africa: Medicines Control CouncilSouth Africa: National Health Research Ethics CouncilItaly: Ethics CommitteeItaly: The Italian Medicines AgencyIndia: Drugs Controller General of IndiaIndia: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1282
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Saxagliptin
Tablets, Oral, 5mg , Once daily, 24 weeks
• Metformin XR
Tablets, Oral, = 1500mg/= 2000mg, Once daily, 24 weeks
• Dapagliflozin
Tablets, Oral, 10mg , Once daily, 24 weeks
• Placebo matching with Dapagliflozin
Tablets, Oral, 0mg, Once daily, 24 weeks
• Placebo matching with Saxagliptin
Tablets, Oral, 0mg, Once daily, 24 weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  Korea, Republic of,  Mexico,  Poland,  Puerto Rico,  Romania,  South Africa, 

References & Publications (1)

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 sa — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in HbA1c at Week 24		Baseline (Week 0) and at Week 24	No
Secondary	Mean Change From Baseline in 2-hour Post-prandial Glucose During a Liquid Meal Test (2-h MTT)		Baseline (Week 0) and at Week 24	No
Secondary	Mean Change From Baseline in Fasting Plasma Glucose (FPG)		Baseline (Week 0) and at Week 24	No
Secondary	Adjusted Percentage of Subjects Achieving Glycemic Response Defined as Glycosylated Hemoglobin (HbA1c) < 7%		At Week 24	No
Secondary	Mean Change From Baseline in Body Weight at Week 24 With the Addition of Saxagliptin and Dapagliflozin to Metformin vs. the Addition of Placebo and Saxagliptin to Metformin		Baseline (Week 0) and at Week 24	No

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   CV_181169_Protocol_Redacted
•   CV181169_Synopsis
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form