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

NCT00327015 | Completed Phase 3 Results DMC

• 1 other identifier: CV181-039
• Study Type: interventional
• Target: 1,306
• Locations: 13 countries
• Sites: 211

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

Conditions

Diabetes

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Hemoglobin A1c (A1C) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

  Mean change from baseline in A1C at Week 24, adjusted for baseline value.

  Baseline, Week 24

• Change From Baseline in A1C at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

  Mean change from baseline in A1C at Week 24, adjusted for baseline value.

  Baseline, Week 24

Secondary Outcomes (10)

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

  Baseline, Week 24

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

  Baseline, Week 24

• Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

  Week 24

• Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

  Week 24

• 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

  Baseline, Week 24

Study Arms (4)

Saxagliptin and Metformin (A)

EXPERIMENTAL

PLUS open-label pioglitazone (as needed as rescue medication)

Drug: Saxagliptin; Drug: Metformin; Drug: pioglitazone

Saxagliptin and Metformin (B)

EXPERIMENTAL

PLUS open-label pioglitazone (as needed as rescue medication)

Drug: Saxagliptin; Drug: Metformin; Drug: pioglitazone

Saxagliptin and Placebo (C)

EXPERIMENTAL

PLUS open-label pioglitazone (as needed as rescue medication)

Drug: Saxagliptin; Drug: Placebo; Drug: pioglitazone

Metformin and Placebo (D)

ACTIVE COMPARATOR

PLUS open-label pioglitazone (as needed as rescue medication)

Drug: Metformin; Drug: Placebo; Drug: pioglitazone

Interventions

Saxagliptin DRUG

Coated Tablets, Oral, 10 mg, Daily (6 months ST, 12 months LT)

Also known as: BMS-477118

Saxagliptin and Metformin (A); Saxagliptin and Placebo (C)

Metformin DRUG

Coated tablets, Oral, 500 mg, Daily (6 months ST, 12 months LT)

Metformin and Placebo (D); Saxagliptin and Metformin (A); Saxagliptin and Metformin (B)

Placebo DRUG

Coated tablets, Oral, 0 mg, Daily (6 months ST, 12 months LT)

Metformin and Placebo (D); Saxagliptin and Placebo (C)

pioglitazone DRUG

Tablets, Oral, 15-45 mg, as needed (12 months LT)

Metformin and Placebo (D); Saxagliptin and Metformin (A); Saxagliptin and Metformin (B); Saxagliptin and Placebo (C)

Eligibility Criteria

• Age: 18 Years - 77 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (211)

East Bay Clinical Trial Center

Concord, California, 94520, United States

Location

Encompass Clinical Research

Encinitas, California, 92024, United States

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Community Clinical Trials

Orange, California, 92868, United States

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Coastal Biomedical Research Inc

Santa Monica, California, 90404, United States

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Encompass Clinical Research

Spring Valley, California, 91978, United States

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St. Joseph'S Medical Associates

Stockton, California, 95204, United States

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Clinical Therapeutics Corporation

Coral Gables, Florida, 33134, United States

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Florida Research Network, Llc

Gainesville, Florida, 32605, United States

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Fpa Clinical Research

Kissimmee, Florida, 34741, United States

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Emerald Coast Research Group

Marianna, Florida, 32446, United States

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Baptist Diabetes Associates

Miami, Florida, 33156, United States

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Middle Georgia Drug Study Center, Llc

Perry, Georgia, 31069, United States

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Cedar Crosse Research Center

Chicago, Illinois, 60607, United States

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Adviso Medical Research, Llc

Chicago, Illinois, 60617, United States

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Deerbrook Medical Associates

Vernon Hills, Illinois, 60061, United States

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Physicians Research Group

Indianapolis, Indiana, 46250, United States

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Professional Network Research Of Kansas

Wichita, Kansas, 67203, United States

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Medical Arts Research Collaborative, Llc

Excelsior Springs, Missouri, 64024, United States

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Nevada Alliance Against Diabetes

North Las Vegas, Nevada, 89030, United States

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Metrolina Medical Research

Charlotte, North Carolina, 28209, United States

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Durham Internal Medicine Assoc.

Durham, North Carolina, 27704, United States

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Down East Medical Associates

Morehead City, North Carolina, 28557, United States

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Midwest Regional Research, Inc.

Bellbrook, Ohio, 45305, United States

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Massillon Family Practice

Massillon, Ohio, 44646, United States

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Your Diabetes Endocrine Nutrition Group

Mentor, Ohio, 44060, United States

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Newark Physician Associates

Newark, Ohio, 43055, United States

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Preferred Primary Care Physicians

Uniontown, Pennsylvania, 15401, United States

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Safe Harbor Clinical Research

East Providence, Rhode Island, 02914, United States

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Internal Medicine Of Greer

Greer, South Carolina, 29651, United States

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Middle Tennessee Clinical Research

Fayetteville, Tennessee, 37334, United States

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Frontier Clinical Research, Llc.

Memphis, Tennessee, 38103, United States

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Capital Medical Clinic, Llp

Austin, Texas, 78705, United States

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Endocrine Associates

Houston, Texas, 77004, United States

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Advances In Health,Inc

Houston, Texas, 77030, United States

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Juno Research, Llc

Houston, Texas, 77036, United States

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Non Invasive Cardiovascular Pa

Houston, Texas, 77074, United States

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Tiena Health Research

Irving, Texas, 75039, United States

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Diabetes Center Of The Southwest

Midland, Texas, 79705, United States

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Hill Country Medical Associates

New Braunfels, Texas, 78130, United States

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Pearland Primary Care Associates, Llp

Pearland, Texas, 77584, United States

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Med-Cure Primary Care Physicians

Rosenberg, Texas, 77471, United States

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Gsa Research

San Antonio, Texas, 78213, United States

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Covenant Clinical Research, Pa

San Antonio, Texas, 78229, United States

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S.A.M. Clinical Research Center

San Antonio, Texas, 78229, United States

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Seven Corners Medical Research Center

Falls Church, Virginia, 22044, United States

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Salem Va Medical Ctr Research & Devlopment

Salem, Virginia, 24153, United States

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Physicians Clinic Of Spokane

Spokane, Washington, 99204, United States

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Local Institution

Belgrano, Buenos Aires, C1426EGP, Argentina

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Buenos Aires, Buenos Aires, 1121, Argentina

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Buenos Aires, Buenos Aires, B7602CBM, Argentina

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Buenos Aires, Buenos Aires, C1117ABH, Argentina

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Buenos Aires, Buenos Aires, C1425AGC, Argentina

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Capital Federal, Buenos Aires, 1221, Argentina

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Capital Federal, Buenos Aires, C1406GWY, Argentina

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Chacabuco, Buenos Aires, 6740, Argentina

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La Plata, Buenos Aires, B1902COS, Argentina

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Morón, Buenos Aires, B1708IFF, Argentina

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San Martín, Buenos Aires, CP1405, Argentina

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San Pedro, Buenos Aires, B2930DGO, Argentina

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Zárate, Buenos Aires, 2800, Argentina

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Mendoza, Mendoza Province, CP5500, Argentina

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Salta, Salta Province, 4406, Argentina

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Salta, Salta Province, A4400EMI, Argentina

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San Juan, San Juan Province, 5400, Argentina

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Rosario, Santa Fe Province, CP2000, Argentina

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Lanus Este, Tucumán Province, 1824, Argentina

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Buenos Aires, C1408INH, Argentina

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Buenos Aires, C1505CWB, Argentina

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Fortaleza, Ceará, 60021, Brazil

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Fortaleza, Ceará, 60430, Brazil

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Goiânia, Goiás, 74110, Brazil

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Belém, Pará, 66073, Brazil

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Recife, Pernambuco, 52051, Brazil

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Porto Alegre, Rio Grande do Sul, 90035, Brazil

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Campinas, São Paulo, 13059, Brazil

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Marília, São Paulo, 17519, Brazil

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São Paulo, São Paulo, 01244, Brazil

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São Paulo, São Paulo, 04020, Brazil

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Aschaffenburg, 63739, Germany

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Bad, 37431, Germany

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Dresden, 01307, Germany

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Dresden, O1219, Germany

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Duisburg, 47051, Germany

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Heidelberg, 69120, Germany

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Künzing, 94550, Germany

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Ludwigshafen, 67073, Germany

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Magdeburg, 39112, Germany

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Mainz, 55116, Germany

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Mannheim, 68161, Germany

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Saarbrücken, 66119, Germany

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Vellmar, 34246, Germany

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Wangen, 88239, Germany

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Eger, 3300, Hungary

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Érd, 2030, Hungary

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Gyula, 5700, Hungary

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Szentes, 6600, Hungary

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Szigetvár, 7900, Hungary

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Panjagutta, Hyderabad, Andhra Pradesh, 500082, India

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Vasanth Nagar, Bangalore, 560052, India

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Bangalore, Karnataka, 560010, India

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Pune, Maharashtra, 411011, India

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Kandivili West, Mumbai, 400067, India

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Sarita Vihar, New Delhi, 110076, India

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Chennai, Tamil Nadu, 680086, India

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Bangalore, 560054, India

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Chennai, 680004, India

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Haryāna, 132001, India

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Rajasthan, 302001, India

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Rajasthan, 334 003, India

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Vellore, Tamilnadu, 632004, India

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Catania, 20099, Italy

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Genova, 16132, Italy

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Milan, 20132, Italy

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Perugia, 06124, Italy

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Ravenna, 48100, Italy

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Aguascalientes, Aguascalientes, 20230, Mexico

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Aguascalientes, Aguascalientes, 20232, Mexico

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Guadalajara, Jalisco, 44340, Mexico

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Guadalajara, Jalisco, 44650, Mexico

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Guadalajara, Jalisco, 44670, Mexico

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Guadalajara, Jalisco, 45030, Mexico

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Guadalajara, Jalisco, 45200, Mexico

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Mexico City, Mexico City, 06700, Mexico

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Cuernavaca, Morelos, 62250, Mexico

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Garza García, Nuevo León, 66260, Mexico

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Monterrey, Nuevo León, 64020, Mexico

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Monterrey, Nuevo León, 64460, Mexico

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Monterrey, Nuevo León, 64570, Mexico

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Mérida, Yucatán, 97070, Mexico

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Cebu City, 6000, Philippines

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Iloilo City, 5000, Philippines

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Manila, 1000, Philippines

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Marikina City, 1800, Philippines

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Pasig, 1605, Philippines

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Quezon City, 1100, Philippines

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Gniewkowo, 88-140, Poland

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Gorzów Wielkopolski, 66-400, Poland

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Izabelin, 05-080, Poland

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Krakow, 31-159, Poland

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Lublin, 20-538, Poland

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Michalow-Regionow, 05-119, Poland

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Warsaw, 03-563, Poland

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Wroclaw, 50-127, Poland

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Zabrze, 41-800, Poland

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Carolina, 00983, Puerto Rico

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Ponce, 00716, Puerto Rico

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Ponce, 00717, Puerto Rico

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Rio Pieoras, 00926, Puerto Rico

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San Juan, 00909, Puerto Rico

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San Juan, 00920, Puerto Rico

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Kemerovo, Russia, 650066, Russia

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Moscow, Russia, 117593, Russia

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Moscow, Russia, 123056, Russia

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Moscow, Russia, 125299, Russia

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Nizhny Novgorod, Russia, 603018, Russia

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Izhevsk, 426000, Russia

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Kirov, 610030, Russia

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Krasnodar, 350012, Russia

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Krasnodar, 350042, Russia

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Kursk, 305035, Russia

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Moscow, 105229, Russia

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Moscow, 115093, Russia

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Moscow, 115280, Russia

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Moscow, 117292, Russia

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Moscow, 119034, Russia

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Moscow, 11992, Russia

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Moscow, 123423, Russia

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Moscow, 125315, Russia

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Moscow, 127486, Russia

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Moscow, 127644, Russia

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Moscow, 129010, Russia

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Moscow, 129119, Russia

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Moscow, 129327, Russia

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Nizhny Novgorod, 603126, Russia

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Novosibirsk, 630047, Russia

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Novosibirsk, 630087, Russia

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Perm, 614095, Russia

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Rostov-on-Don, 344022, Russia

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Rostov-on-Don, 344029, Russia

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Saint Peterburg, 195257, Russia

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Saint Petersburg, 191119, Russia

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Saint Petersburg, 192177, Russia

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Saint Petersburg, 193015, Russia

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Saint Petersburg, 193312, Russia

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Saint Petersburg, 194354, Russia

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Saint Petersburg, 195112, Russia

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Saint Petersburg, 195176, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, 197198, Russia

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Saint Petersburg, 198013, Russia

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Saratov, 410024, Russia

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Saratov, 410028, Russia

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Saratov, 410053, Russia

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Saratov, 410054, Russia

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Smolensk, 214018, Russia

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Tuymen, 625023, Russia

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Vladimir, 600023, Russia

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Volgograd, 400001, Russia

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Volgograd, 400107, Russia

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Yaroslaval, 150003, Russia

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Yaroslavl, 150003, Russia

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Dniepropetrovsk, 49044, Ukraine

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Kharkiv, 61039, Ukraine

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Kharkiv, 61176, Ukraine

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Kyiv, 03680, Ukraine

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Kyiv, 4050, Ukraine

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Lutsk, 43024, Ukraine

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Lviv, 790015, Ukraine

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Lviv, 79013, Ukraine

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Odesa, 65025, Ukraine

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Ternopil, 46001, Ukraine

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Related Publications (5)

• 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.

  PMID: 19515181 BACKGROUND

• 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.

  PMID: 32501595 DERIVED

• 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.

  PMID: 25414932 DERIVED

• 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.

  PMID: 23795975 DERIVED

• 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.

  PMID: 21342412 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

saxagliptin; Metformin; Pioglitazone

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Thiazolidinediones; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boaz Hirschberg
• Organization: AstraZeneca Pharmaceuticals

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2006
• First Posted: May 17, 2006
• Study Start: May 1, 2006
• Primary Completion: November 1, 2007
• Study Completion: December 1, 2008
• Last Updated: April 29, 2015
• Results First Posted: September 25, 2009

Record last verified: 2015-03

Locations

UA (10); IN (13); DE (14); PL (9); IT (5); US (47); AR (21); ME (14); PR (6); RU (51); BR (10); HU (5); PH (6)