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

Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00327015
• Other study ID #: CV181-039
• Status: Completed
• Phase: Phase 3
• First received: May 15, 2006
• Last updated: April 8, 2015
• Start date: May 2006
• Est. completion date: December 2008

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1306
• Est. completion date: December 2008
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 77 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Diabetes

Intervention

Drug:
• Saxagliptin
Coated Tablets, Oral, 10 mg, Daily (6 months ST, 12 months LT)
• Saxagliptin
Coated tablets, PO, 5 mg, Daily (6 months ST, 12 months LT)
• Metformin
Coated tablets, Oral, 500 mg, Daily (6 months ST, 12 months LT)
• Placebo
Coated tablets, Oral, 0 mg, Daily (6 months ST, 12 months LT)
• pioglitazone
Tablets, Oral, 15-45 mg, as needed (12 months LT)

Locations

Country	Name	City	State
Argentina	Local Institution	Belgrano	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Chacabuco	Buenos Aires
Argentina	Local Institution	La Plata	Buenos Aires
Argentina	Local Institution	Lanus Este	Tucuman
Argentina	Local Institution	Mendoza
Argentina	Local Institution	Moron	Buenos Aires
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	Salta
Argentina	Local Institution	Salta
Argentina	Local Institution	San Juan
Argentina	Local Institution	San Martin	Buenos Aires
Argentina	Local Institution	San Pedro	Buenos Aires
Argentina	Local Institution	Zarate	Buenos Aires
Brazil	Local Institution	Belem	Para
Brazil	Local Institution	Campinas	Sao Paulo
Brazil	Local Institution	Fortaleza	Ceara
Brazil	Local Institution	Fortaleza	Ceara
Brazil	Local Institution	Goiania	Goias
Brazil	Local Institution	Marília	Sao Paulo
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Recife	Pe
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Germany	Local Institution	Aschaffenburg
Germany	Local Institution	Bad
Germany	Local Institution	Dresden
Germany	Local Institution	Dresden
Germany	Local Institution	Duisburg
Germany	Local Institution	Heidelberg
Germany	Local Institution	Kuenzing
Germany	Local Institution	Ludwigshafen
Germany	Local Institution	Magdeburg
Germany	Local Institution	Mainz
Germany	Local Institution	Mannheim
Germany	Local Institution	Saarbrücken
Germany	Local Institution	Vellmar
Germany	Local Institution	Wangen Im Allgau
Hungary	Local Institution	Eger
Hungary	Local Institution	Érd
Hungary	Local Institution	Gyula
Hungary	Local Institution	Szentes
Hungary	Local Institution	Szigetvár
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Bangalore
India	Local Institution	Chennai
India	Local Institution	Chennai	Tamil Nadu
India	Local Institution	Haryana
India	Local Institution	Kandivili West	Mumbai
India	Local Institution	Panjagutta, Hyderabad	Andhra Pradesh
India	Local Institution	Pune	Maharashtra
India	Local Institution	Rajasthan
India	Local Institution	Rajasthan
India	Local Institution	Sarita Vihar	New Delhi
India	Local Institution	Vasanth Nagar	Bangalore
India	Local Institution	Vellore, Tamilnadu
Italy	Local Institution	Catania
Italy	Local Institution	Genova
Italy	Local Institution	Milano
Italy	Local Institution	Perugia
Italy	Local Institution	Ravenna
Mexico	Local Institution	Aguascalientes
Mexico	Local Institution	Aguascalientes
Mexico	Local Institution	Cuernavaca	Morelos
Mexico	Local Institution	Garza Garcia	Nuevo Leon
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Merida	Yucatan
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Monterrey	Nuevo Leon
Philippines	Local Institution	Cebu City
Philippines	Local Institution	Iloilo City
Philippines	Local Institution	Manila City
Philippines	Local Institution	Marikina City
Philippines	Local Institution	Pasig City
Philippines	Local Institution	Quezon City
Poland	Local Institution	Gniewkowo
Poland	Local Institution	Gorzow Wielkopolski
Poland	Local Institution	Izabelin
Poland	Local Institution	Krakow
Poland	Local Institution	Lublin
Poland	Local Institution	Michalow-Regionow
Poland	Local Institution	Warszawa
Poland	Local Institution	Wroclaw
Poland	Local Institution	Zabrze
Puerto Rico	Local Institution	Carolina
Puerto Rico	Local Institution	Ponce
Puerto Rico	Local Institution	Ponce
Puerto Rico	Local Institution	Rio Pieoras
Puerto Rico	Local Institution	San Juan
Puerto Rico	Local Institution	San Juan
Russian Federation	Local Institution	Izhevsk
Russian Federation	Local Institution	Kemerovo	Russia
Russian Federation	Local Institution	Kirov
Russian Federation	Local Institution	Krasnodar
Russian Federation	Local Institution	Krasnodar
Russian Federation	Local Institution	Kursk
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow	Russia
Russian Federation	Local Institution	Moscow	Russia
Russian Federation	Local Institution	Moscow	Russia
Russian Federation	Local Institution	Nizhniy Novgorod	Russia
Russian Federation	Local Institution	Nizhniy Novgorod
Russian Federation	Local Institution	Novosibirsk
Russian Federation	Local Institution	Novosibirsk
Russian Federation	Local Institution	Perm
Russian Federation	Local Institution	Rostov-Na-Donu
Russian Federation	Local Institution	Rostov-Na-Donu
Russian Federation	Local Institution	Saint Petersburg
Russian Federation	Local Institution	Saratov
Russian Federation	Local Institution	Saratov
Russian Federation	Local Institution	Saratov
Russian Federation	Local Institution	Saratov
Russian Federation	Local Institution	Smolensk
Russian Federation	Local Institution	St Petersburg
Russian Federation	Local Institution	St-Petersburg
Russian Federation	Local Institution	St. Peterburg
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St.Petersburg
Russian Federation	Local Institution	St.Petersburg
Russian Federation	Local Institution	St.Petersburg
Russian Federation	Local Institution	St.Petersburg
Russian Federation	Local Institution	Tuymen
Russian Federation	Local Institution	Vladimir
Russian Federation	Local Institution	Volgograd
Russian Federation	Local Institution	Volgograd
Russian Federation	Local Institution	Yaroslaval
Russian Federation	Local Institution	Yaroslavl
Ukraine	Local Institution	Dniepropetrovsk
Ukraine	Local Institution	Kharkiv
Ukraine	Local Institution	Kharkiv
Ukraine	Local Institution	Kyiv
Ukraine	Local Institution	Kyiv
Ukraine	Local Institution	Lutsk
Ukraine	Local Institution	Lviv
Ukraine	Local Institution	Lviv
Ukraine	Local Institution	Odessa
Ukraine	Local Institution	Ternopil
United States	Capital Medical Clinic, Llp	Austin	Texas
United States	Midwest Regional Research, Inc.	Bellbrook	Ohio
United States	Metrolina Medical Research	Charlotte	North Carolina
United States	Adviso Medical Research, Llc	Chicago	Illinois
United States	Cedar Crosse Research Center	Chicago	Illinois
United States	East Bay Clinical Trial Center	Concord	California
United States	Clinical Therapeutics Corporation	Coral Gables	Florida
United States	Durham Internal Medicine Assoc.	Durham	North Carolina
United States	Safe Harbor Clinical Research	E. Providence	Rhode Island
United States	Encompass Clinical Research	Encinitas	California
United States	Medical Arts Research Collaborative, Llc	Excelsior Springs	Missouri
United States	Seven Corners Medical Research Center	Falls Church	Virginia
United States	Middle Tennessee Clinical Research	Fayetteville	Tennessee
United States	Florida Research Network, Llc	Gainesville	Florida
United States	Internal Medicine Of Greer	Greer	South Carolina
United States	Advances In Health,Inc	Houston	Texas
United States	Endocrine Associates	Houston	Texas
United States	Juno Research, Llc	Houston	Texas
United States	Non Invasive Cardiovascular Pa	Houston	Texas
United States	Physicians Research Group	Indianapolis	Indiana
United States	Tiena Health Research	Irving	Texas
United States	Fpa Clinical Research	Kissimmee	Florida
United States	Emerald Coast Research Group	Marianna	Florida
United States	Massillon Family Practice	Massillon	Ohio
United States	Frontier Clinical Research, Llc.	Memphis	Tennessee
United States	Your Diabetes Endocrine Nutrition Group	Mentor	Ohio
United States	Baptist Diabetes Associates	Miami	Florida
United States	Diabetes Center Of The Southwest	Midland	Texas
United States	Down East Medical Associates	Morehead City	North Carolina
United States	Nevada Alliance Against Diabetes	N. Las Vegas	Nevada
United States	Hill Country Medical Associates	New Braunfels	Texas
United States	Newark Physician Associates	Newark	Ohio
United States	Community Clinical Trials	Orange	California
United States	Pearland Primary Care Associates, Llp	Pearland	Texas
United States	Middle Georgia Drug Study Center, Llc	Perry	Georgia
United States	Med-Cure Primary Care Physicians	Rosenberg	Texas
United States	Salem Va Medical Ctr Research & Devlopment	Salem	Virginia
United States	Covenant Clinical Research, Pa	San Antonio	Texas
United States	Gsa Research	San Antonio	Texas
United States	S.A.M. Clinical Research Center	San Antonio	Texas
United States	Coastal Biomedical Research Inc	Santa Monica	California
United States	Physicians Clinic Of Spokane	Spokane	Washington
United States	Encompass Clinical Research	Spring Valley	California
United States	St. Joseph'S Medical Associates	Stockton	California
United States	Preferred Primary Care Physicians	Uniontown	Pennsylvania
United States	Deerbrook Medical Associates	Vernon Hills	Illinois
United States	Professional Network Research Of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Germany,  Hungary,  India,  Italy,  Mexico,  Philippines,  Poland,  Puerto Rico,  Russian Federation,  Ukraine, 

References & Publications (1)

Jadzinsky M, Pfützner 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy	Mean change from baseline in FPG at Week 24, adjusted for baseline value.	Baseline, Week 24	No
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy	Mean change from baseline in FPG at Week 24, adjusted for baseline value.	Baseline, Week 24	No
Secondary	Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy	Percentage of participants achieving A1C < 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24.	Week 24	No
Secondary	Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy	Percentage of participants achieving A1C < 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus metformin versus metformin alone at Week 24.	Week 24	No
Secondary	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	Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjusted for baseline value.	Baseline, Week 24	No
Secondary	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	Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjsuted for baseline value.	Baseline, Week 24	No
Secondary	Percentage of Participants Achieving A1C =6.5% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy	Percentage of participants achieving A1C =6.5%, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24.	Week 24	No
Secondary	Percentage of Participants Achieving A1C =6.5% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy	Percentage of participants achieving A1C =6.5%, at each dose of saxagliptin plus metformin versus metformin alone at Week 24.	Week 24	No
Secondary	Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy	Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus saxagliptin alone.	Week 24	No
Secondary	Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy	Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus metformin alone.	Week 24	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm