Clinical trial NCT00327015: A Phase 3 Study of BMS-477118 in Combination With Metformin in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise
Official title: A Multicenter, Randomized, Double-Blind Active-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination With Metformin IR as Initial Therapy Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2006-05-17
Enrollment: 1306
Sex: ALL
Minimum age (years): 18
Maximum age (years): 77
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to understand if adding saxagliptin to metformin therapy is safe and works better than taking either saxagliptin or metformin alone

Detailed description: All subjects will participate in a lead-in period, and qualifying subjects will continue into a short-term randomized treatment period. Subjects who complete the short-term period will be eligible to enter the long term extension period. Also, subjects in the short-term period who have an elevated blood sugar that requires additional medication for blood sugar control will be eligible to enter the long-term treatment extension period where they will receive pioglitazone (rescue medication) added onto their blinded study medication

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes
* Inadequate blood sugar control
* No current treatment with other medications to lower blood sugar

Exclusion Criteria:

* Major heart, liver or kidney problems
* Pregnant or breast feeding

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (A1C) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
timeFrame: Baseline, Week 24
measure: Change From Baseline in A1C at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
timeFrame: Baseline, Week 24
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
timeFrame: Baseline, Week 24
measure: Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
timeFrame: Week 24
measure: Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
timeFrame: Week 24
measure: Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
timeFrame: Baseline, Week 24
measure: Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
timeFrame: Baseline, Week 24
measure: Percentage of Participants Achieving A1C ≤6.5% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
timeFrame: Week 24
measure: Percentage of Participants Achieving A1C ≤6.5% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
timeFrame: Week 24
measure: Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy
timeFrame: Week 24
measure: Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy
timeFrame: Week 24
Other outcomes:
Locations:
city: Concord
country: United States
facility: East Bay Clinical Trial Center
state: California
city: Encinitas
country: United States
facility: Encompass Clinical Research
state: California
city: Orange
country: United States
facility: Community Clinical Trials
state: California
city: Santa Monica
country: United States
facility: Coastal Biomedical Research Inc
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Stockton
country: United States
facility: St. Joseph'S Medical Associates
state: California
city: Coral Gables
country: United States
facility: Clinical Therapeutics Corporation
state: Florida
city: Gainesville
country: United States
facility: Florida Research Network, Llc
state: Florida
city: Kissimmee
country: United States
facility: Fpa Clinical Research
state: Florida
city: Marianna
country: United States
facility: Emerald Coast Research Group
state: Florida
city: Miami
country: United States
facility: Baptist Diabetes Associates
state: Florida
city: Perry
country: United States
facility: Middle Georgia Drug Study Center, Llc
state: Georgia
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Chicago
country: United States
facility: Adviso Medical Research, Llc
state: Illinois
city: Vernon Hills
country: United States
facility: Deerbrook Medical Associates
state: Illinois
city: Indianapolis
country: United States
facility: Physicians Research Group
state: Indiana
city: Wichita
country: United States
facility: Professional Network Research Of Kansas
state: Kansas
city: Excelsior Springs
country: United States
facility: Medical Arts Research Collaborative, Llc
state: Missouri
city: N. Las Vegas
country: United States
facility: Nevada Alliance Against Diabetes
state: Nevada
city: Charlotte
country: United States
facility: Metrolina Medical Research
state: North Carolina
city: Durham
country: United States
facility: Durham Internal Medicine Assoc.
state: North Carolina
city: Morehead City
country: United States
facility: Down East Medical Associates
state: North Carolina
city: Bellbrook
country: United States
facility: Midwest Regional Research, Inc.
state: Ohio
city: Massillon
country: United States
facility: Massillon Family Practice
state: Ohio
city: Mentor
country: United States
facility: Your Diabetes Endocrine Nutrition Group
state: Ohio
city: Newark
country: United States
facility: Newark Physician Associates
state: Ohio
city: Uniontown
country: United States
facility: Preferred Primary Care Physicians
state: Pennsylvania
city: E. Providence
country: United States
facility: Safe Harbor Clinical Research
state: Rhode Island
city: Greer
country: United States
facility: Internal Medicine Of Greer
state: South Carolina
city: Fayetteville
country: United States
facility: Middle Tennessee Clinical Research
state: Tennessee
city: Memphis
country: United States
facility: Frontier Clinical Research, Llc.
state: Tennessee
city: Austin
country: United States
facility: Capital Medical Clinic, Llp
state: Texas
city: Houston
country: United States
facility: Endocrine Associates
state: Texas
city: Houston
country: United States
facility: Advances In Health,Inc
state: Texas
city: Houston
country: United States
facility: Juno Research, Llc
state: Texas
city: Houston
country: United States
facility: Non Invasive Cardiovascular Pa
state: Texas
city: Irving
country: United States
facility: Tiena Health Research
state: Texas
city: Midland
country: United States
facility: Diabetes Center Of The Southwest
state: Texas
city: New Braunfels
country: United States
facility: Hill Country Medical Associates
state: Texas
city: Pearland
country: United States
facility: Pearland Primary Care Associates, Llp
state: Texas
city: Rosenberg
country: United States
facility: Med-Cure Primary Care Physicians
state: Texas
city: San Antonio
country: United States
facility: Gsa Research
state: Texas
city: San Antonio
country: United States
facility: Covenant Clinical Research, Pa
state: Texas
city: San Antonio
country: United States
facility: S.A.M. Clinical Research Center
state: Texas
city: Falls Church
country: United States
facility: Seven Corners Medical Research Center
state: Virginia
city: Salem
country: United States
facility: Salem Va Medical Ctr Research & Devlopment
state: Virginia
city: Spokane
country: United States
facility: Physicians Clinic Of Spokane
state: Washington
city: Belgrano
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Chacabuco
country: Argentina
facility: Local Institution
state: Buenos Aires
city: La Plata
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Moron
country: Argentina
facility: Local Institution
state: Buenos Aires
city: San Martin
country: Argentina
facility: Local Institution
state: Buenos Aires
city: San Pedro
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Zarate
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Rosario
country: Argentina
facility: Local Institution
state: Santa Fe
city: Lanus Este
country: Argentina
facility: Local Institution
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Mendoza
country: Argentina
facility: Local Institution
city: Salta
country: Argentina
facility: Local Institution
city: Salta
country: Argentina
facility: Local Institution
city: San Juan
country: Argentina
facility: Local Institution
city: Fortaleza
country: Brazil
facility: Local Institution
state: Ceara
city: Fortaleza
country: Brazil
facility: Local Institution
state: Ceara
city: Goiania
country: Brazil
facility: Local Institution
state: Goias
city: Belem
country: Brazil
facility: Local Institution
state: Para
city: Recife
country: Brazil
facility: Local Institution
state: Pe
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Marília
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Aschaffenburg
country: Germany
facility: Local Institution
city: Bad
country: Germany
facility: Local Institution
city: Dresden
country: Germany
facility: Local Institution
city: Dresden
country: Germany
facility: Local Institution
city: Duisburg
country: Germany
facility: Local Institution
city: Heidelberg
country: Germany
facility: Local Institution
city: Kuenzing
country: Germany
facility: Local Institution
city: Ludwigshafen
country: Germany
facility: Local Institution
city: Magdeburg
country: Germany
facility: Local Institution
city: Mainz
country: Germany
facility: Local Institution
city: Mannheim
country: Germany
facility: Local Institution
city: Saarbrücken
country: Germany
facility: Local Institution
city: Vellmar
country: Germany
facility: Local Institution
city: Wangen Im Allgau
country: Germany
facility: Local Institution
city: Eger
country: Hungary
facility: Local Institution
city: Gyula
country: Hungary
facility: Local Institution
city: Szentes
country: Hungary
facility: Local Institution
city: Szigetvár
country: Hungary
facility: Local Institution
city: Érd
country: Hungary
facility: Local Institution
city: Panjagutta, Hyderabad
country: India
facility: Local Institution
state: Andhra Pradesh
city: Vasanth Nagar
country: India
facility: Local Institution
state: Bangalore
city: Bangalore
country: India
facility: Local Institution
state: Karnataka
city: Pune
country: India
facility: Local Institution
state: Maharashtra
city: Kandivili West
country: India
facility: Local Institution
state: Mumbai
city: Sarita Vihar
country: India
facility: Local Institution
state: New Delhi
city: Chennai
country: India
facility: Local Institution
state: Tamil Nadu
city: Bangalore
country: India
facility: Local Institution
city: Chennai
country: India
facility: Local Institution
city: Haryana
country: India
facility: Local Institution
city: Rajasthan
country: India
facility: Local Institution
city: Rajasthan
country: India
facility: Local Institution
city: Vellore, Tamilnadu
country: India
facility: Local Institution
city: Catania
country: Italy
facility: Local Institution
city: Genova
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Perugia
country: Italy
facility: Local Institution
city: Ravenna
country: Italy
facility: Local Institution
city: Mexico
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Cuernavaca
country: Mexico
facility: Local Institution
state: Morelos
city: Garza Garcia
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
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: Aguascalientes
country: Mexico
facility: Local Institution
city: Cebu City
country: Philippines
facility: Local Institution
city: Iloilo City
country: Philippines
facility: Local Institution
city: Manila City
country: Philippines
facility: Local Institution
city: Marikina City
country: Philippines
facility: Local Institution
city: Pasig City
country: Philippines
facility: Local Institution
city: Quezon City
country: Philippines
facility: Local Institution
city: Gniewkowo
country: Poland
facility: Local Institution
city: Gorzow Wielkopolski
country: Poland
facility: Local Institution
city: Izabelin
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lublin
country: Poland
facility: Local Institution
city: Michalow-Regionow
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Wroclaw
country: Poland
facility: Local Institution
city: Zabrze
country: Poland
facility: Local Institution
city: Carolina
country: Puerto Rico
facility: Local Institution
city: Ponce
country: Puerto Rico
facility: Local Institution
city: Ponce
country: Puerto Rico
facility: Local Institution
city: Rio Pieoras
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: Kemerovo
country: Russian Federation
facility: Local Institution
state: Russia
city: Moscow
country: Russian Federation
facility: Local Institution
state: Russia
city: Moscow
country: Russian Federation
facility: Local Institution
state: Russia
city: Moscow
country: Russian Federation
facility: Local Institution
state: Russia
city: Nizhniy Novgorod
country: Russian Federation
facility: Local Institution
state: Russia
city: Izhevsk
country: Russian Federation
facility: Local Institution
city: Kirov
country: Russian Federation
facility: Local Institution
city: Krasnodar
country: Russian Federation
facility: Local Institution
city: Krasnodar
country: Russian Federation
facility: Local Institution
city: Kursk
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Nizhniy Novgorod
country: Russian Federation
facility: Local Institution
city: Novosibirsk
country: Russian Federation
facility: Local Institution
city: Novosibirsk
country: Russian Federation
facility: Local Institution
city: Perm
country: Russian Federation
facility: Local Institution
city: Rostov-Na-Donu
country: Russian Federation
facility: Local Institution
city: Rostov-Na-Donu
country: Russian Federation
facility: Local Institution
city: Saint Petersburg
country: Russian Federation
facility: Local Institution
city: Saratov
country: Russian Federation
facility: Local Institution
city: Saratov
country: Russian Federation
facility: Local Institution
city: Saratov
country: Russian Federation
facility: Local Institution
city: Saratov
country: Russian Federation
facility: Local Institution
city: Smolensk
country: Russian Federation
facility: Local Institution
city: St Petersburg
country: Russian Federation
facility: Local Institution
city: St-Petersburg
country: Russian Federation
facility: Local Institution
city: St. Peterburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St.Petersburg
country: Russian Federation
facility: Local Institution
city: St.Petersburg
country: Russian Federation
facility: Local Institution
city: St.Petersburg
country: Russian Federation
facility: Local Institution
city: St.Petersburg
country: Russian Federation
facility: Local Institution
city: Tuymen
country: Russian Federation
facility: Local Institution
city: Vladimir
country: Russian Federation
facility: Local Institution
city: Volgograd
country: Russian Federation
facility: Local Institution
city: Volgograd
country: Russian Federation
facility: Local Institution
city: Yaroslaval
country: Russian Federation
facility: Local Institution
city: Yaroslavl
country: Russian Federation
facility: Local Institution
city: Dniepropetrovsk
country: Ukraine
facility: Local Institution
city: Kharkiv
country: Ukraine
facility: Local Institution
city: Kharkiv
country: Ukraine
facility: Local Institution
city: Kyiv
country: Ukraine
facility: Local Institution
city: Kyiv
country: Ukraine
facility: Local Institution
city: Lutsk
country: Ukraine
facility: Local Institution
city: Lviv
country: Ukraine
facility: Local Institution
city: Lviv
country: Ukraine
facility: Local Institution
city: Odessa
country: Ukraine
facility: Local Institution
city: Ternopil
country: Ukraine
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Jadzinsky M, Pfutzner A, Paz-Pacheco E, Xu Z, Allen E, Chen R; CV181-039 Investigators. Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab. 2009 Jun;11(6):611-22. doi: 10.1111/j.1463-1326.2009.01056.x.
citation: Gnesin F, Thuesen ACB, Kahler LKA, Madsbad S, Hemmingsen B. Metformin monotherapy for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Jun 5;6(6):CD012906. doi: 10.1002/14651858.CD012906.pub2.
citation: Cook W, Minervini G, Bryzinski B, Hirshberg B. Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials. Postgrad Med. 2014 Oct;126(6):19-32. doi: 10.3810/pgm.2014.10.2818.
citation: Karyekar CS, Frederich R, Ravichandran S. Clinically relevant reductions in HbA1c without hypoglycaemia: results across four studies of saxagliptin. Int J Clin Pract. 2013 Aug;67(8):759-67. doi: 10.1111/ijcp.12212. Epub 2013 Jun 24.
citation: Pfutzner A, Paz-Pacheco E, Allen E, Frederich R, Chen R; CV181039 Investigators. Initial combination therapy with saxagliptin and metformin provides sustained glycaemic control and is well tolerated for up to 76 weeks. Diabetes Obes Metab. 2011 Jun;13(6):567-76. doi: 10.1111/j.1463-1326.2011.01385.x.