Study Assessing Saxagliptin Treatment In Type 2 Diabetic Subjects Who Are Not Controlled With Metformin Alone

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

"A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial to Evaluate the Efficacy and Safety of BMS-477118 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: NCT00121667
• Other study ID #: CV181-014
• Status: Completed
• Phase: Phase 3
• First received: July 18, 2005
• Last updated: April 8, 2015
• Start date: August 2005
• Est. completion date: February 2010

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical research study is to learn whether Saxagliptin added to Metformin therapy is more effective than Metformin alone as a treatment for type 2 diabetic subjects who are not sufficiently controlled with 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 pioglitizone added onto their blinded study medication

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1462
• Est. completion date: February 2010
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 77 Years

Eligibility

Inclusion Criteria:

• Type 2 diabetes mellitus requiring treatment with at least 1500 mg but not greater than 2550 mg of a maximum tolerated dose of Metformin therapy for at least 8 weeks prior to screening.

• HbA1c >= 7.0% and <= 10.0 %

• Body mass index <= 40 kg/m2

• Fasting C-peptide >= 1 ng/dL

Exclusion Criteria:

• Symptomatic poorly controlled diabetes

• Recent cardiac or cerebrovascular event

• Serum creatinine >= 1.5 mg/dL for males and >= 1.4 mg/dL for females

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Saxagliptin + Metformin
Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)
• Saxagliptin + Metformin
Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)
• Saxagliptin + Metformin
Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)
• Placebo + Metformin
Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT)
• Pioglitazone
Tablets, Oral, 15 - 45 mg (as needed for rescue)

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Mar Del Plata	Buenos Aires
Argentina	Local Institution	Rosario	Santa Fe
Australia	Local Institution	Adelaide	South Australia
Australia	Local Institution	Brisbane	Queensland
Australia	Local Institution	Kippa Ring	Queensland
Australia	Local Institution	Meadowbrook	Queensland
Australia	Local Institution	Perth	Western Australia
Australia	Local Institution	Sydney	New South Wales
Australia	Local Institution	Woodville South	South Australia
Australia	Local Institution	Woollongong	New South Wales
Brazil	Local Institution	Belem	Para
Brazil	Local Institution	Campinas	Sao Paulo
Brazil	Local Institution	Fortaleza	Ceara
Brazil	Local Institution	Marilia	Sao Paulo
Brazil	Local Institution	Porto alegre	Rio Grande Do Sul
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Aylmer	Ontario
Canada	Local Institution	Bathurst	New Brunswick
Canada	Local Institution	Brandon	Manitoba
Canada	Local Institution	Calgary	Alberta
Canada	Local Institution	Charlottetown	Prince Edward Island
Canada	Local Institution	Coquitlam	British Columbia
Canada	Local Institution	Drummondville	Quebec
Canada	Local Institution	Fleurimont	Quebec
Canada	Local Institution	Kelowna	British Columbia
Canada	Local Institution	London	Ontario
Canada	Local Institution	Longueuil	Quebec
Canada	Local Institution	Mount Pearl	Newfoundland and Labrador
Canada	Local Institution	Oakville	Ontario
Canada	Local Institution	Portage La Prairie	Manitoba
Canada	Local Institution	Sarnia	Ontario
Canada	Local Institution	Saskatoon	Saskatchewan
Canada	Local Institution	St. John's	Newfoundland and Labrador
Canada	Local Institution	St. Johns	Newfoundland and Labrador
Canada	Local Institution	St. Leonard	Quebec
Canada	Local Institution	Surrey	British Columbia
Canada	Local Institution	Thornhill	Ontario
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Winnipeg	Manitoba
Canada	Local Institution	Woodstock	Ontario
Chile	Local Institution	Santiago	Metropolitana
Chile	Local Institution	Santiago De Chile	Metropolitana
Mexico	Local Institution	Celaya	Guanajuato
Mexico	Local Institution	Distrito Federal
Mexico	Local Institution	Durango
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Hermosillo	Sonora
Mexico	Local Institution	Merida	Yucatan
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Morelia	Michioacan
Puerto Rico	Local Institution	Carolina
Puerto Rico	Local Institution	Ponce
Puerto Rico	Local Institution	Rio Pieoras
Puerto Rico	Local Institution	San Juan
Taiwan	Local Institution	Hualien
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taipei
United States	Local Institution	Albuquerque	New Mexico
United States	Local Institution	Altamonte Springs	Florida
United States	Local Institution	Anniston	Alabama
United States	Local Institution	Athens	Ohio
United States	Local Institution	Austin	Texas
United States	Local Institution	Baltimore	Maryland
United States	Local Institution	Birmingham	Alabama
United States	Local Institution	Boston	Massachusetts
United States	Local Institution	Bristol	Tennessee
United States	Local Institution	Bryan	Texas
United States	Local Institution	Calera	Alabama
United States	Local Institution	Carlisle	Pennsylvania
United States	Local Institution	Carrollton	Texas
United States	Local Institution	Castle Rock	Colorado
United States	Local Institution	Charleston	South Carolina
United States	Local Institution	Charlotte	North Carolina
United States	Local Institution	Chester	Maryland
United States	Local Institution	Chicago	Illinois
United States	Local Institution	Chipley	Florida
United States	Local Institution	Cocoa Beach	Florida
United States	Local Institution	Colorado Springs	Colorado
United States	Local Institution	Columbus	Ohio
United States	Local Institution	Coral Gables	Florida
United States	Local Institution	Dallas	Texas
United States	Local Institution	Decatur	Georgia
United States	Local Institution	Denver	Colorado
United States	Local Institution	Duncan	South Carolina
United States	Local Institution	Elkhart	Indiana
United States	Local Institution	Encino	California
United States	Local Institution	Eugene	Oregon
United States	Local Institution	Fort Lauderdale	Florida
United States	Local Institution	Fountain Valley	California
United States	Local Institution	Fresno	California
United States	Local Institution	Golden	Colorado
United States	Local Institution	Greensboro	North Carolina
United States	Local Institution	Haleyville	Alabama
United States	Local Institution	Hampton	Virginia
United States	Local Institution	Houston	Texas
United States	Local Institution	Iowa City	Iowa
United States	Local Institution	Jacksonville	Florida
United States	Local Institution	Jonesboro	Arkansas
United States	Local Institution	Kalispell	Montana
United States	Local Institution	Kansas City	Missouri
United States	Local Institution	Kissimmee	Florida
United States	Local Institution	Lafayette	Indiana
United States	Local Institution	Langhorne	Pennsylvania
United States	Local Institution	Las Vegas	Nevada
United States	Local Institution	Levittown	Pennsylvania
United States	Local Institution	Lexington	Kentucky
United States	Local Institution	Little Rock	Arkansas
United States	Local Institution	Los Angeles	California
United States	Local Institution	Loveland	Colorado
United States	Local Institution	Lyndhurst	Ohio
United States	Local Institution	Marianna	Florida
United States	Local Institution	Mesa	Arizona
United States	Local Institution	Miami	Florida
United States	Local Institution	Mission Viejo	California
United States	Local Institution	Morehead City	North Carolina
United States	Local Institution	Munfordville	Kentucky
United States	Local Institution	New Orleans	Louisiana
United States	Local Institution	New Port Richey	Florida
United States	Local Institution	Northridge	California
United States	Local Institution	Ocala	Florida
United States	Local Institution	Oklahoma City	Oklahoma
United States	Local Institution	Olympia	Washington
United States	Local Institution	Omaha	Nebraska
United States	Local Institution	Orange	California
United States	Local Institution	Philadelphia	Pennsylvania
United States	Local Institution	Phoenix	Arizona
United States	Local Institution	Pittsburgh	Pennsylvania
United States	Local Institution	Portland	Oregon
United States	Local Institution	Prince Frederick	Maryland
United States	Local Institution	Roseville	California
United States	Local Institution	Sacramento	California
United States	Local Institution	Salisbury	North Carolina
United States	Local Institution	Salt Lake City	Utah
United States	Local Institution	San Antonio	Texas
United States	Local Institution	Sherwood	Arkansas
United States	Local Institution	Sparta	North Carolina
United States	Local Institution	Spokane	Washington
United States	Local Institution	Spring Valley	California
United States	Local Institution	St. Louis	Missouri
United States	Local Institution	Tallahassee	Florida
United States	Local Institution	Tampa	Florida
United States	Local Institution	Temple	Texas
United States	Local Institution	Toms River	New Jersey
United States	Local Institution	Topeka	Kansas
United States	Local Institution	Tulsa	Oklahoma
United States	Local Institution	Tustin	California
United States	Local Institution	Vernon Hills	Illinois
United States	Local Institution	Virginia Beach	Virginia
United States	Local Institution	Waterloo	Iowa
United States	Local Institution	West Monroe	Louisiana
United States	Local Institution	Wilmington	North Carolina
United States	Local Institution	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  Mexico,  Puerto Rico,  Taiwan, 

References & Publications (1)

DeFronzo RA, Hissa MN, Garber AJ, Luiz Gross J, Yuyan Duan R, Ravichandran S, Chen RS; Saxagliptin 014 Study Group. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care. 2009 Sep;32(9):1649-55. doi: 10.2337/dc08-1984. Epub 2009 May 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Summary of Adverse Events During ST+LT Treatment Period	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related events=relationship of certain, probable, possible, or missing.	AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla
Other	Marked Laboratory Abnormalities - During ST + LT Treatment Period	A laboratory value was considered a marked abnormality if it is outside the pre-defined criteria for marked abnormality and the on-treatment value was more extreme (farther from the limit) than the baseline value. Pre-Rx=pretreatment; ULN=upper limit of normal; ALP=alkaline phosphatase; AST=aspartate aminotransferase; ALT=alanine aminotransferase; unspec=unspecified; sodium serum low: <0.9 x Pre-Rx & <=130mEq/L / high: >1.1 x Pre-Rx & >=150mEq/L; potassium, serum low: <=0.8 x Pre-Rx & >=6.0mEq/L / high: 1.2 x Pre-Rx & >=6.0mEq/L; LLN=lower limit of normal.	Lab assessments taken during and up to 14 days after the last dose of study drug during the ST + LT Treatment Period. Mean duration of exposure: 124, 118, 130, 95 weeks, respectively, for 2.5mg, 5mg, 10 mg, placebo.
Other	Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period		Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Baseline and Changes From Baseline in Hematocrit During the ST + LT Period		Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Baseline and Changes From Baseline in Red Blood Cell Counts (x 10^6 c/µL) During the ST + LT Period		Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Baseline and Changes From Baseline in Platelet Counts (x 10^9 c/L) During the ST + LT Period		Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Baseline and Changes From Baseline in White Blood Cell Counts (x 10^3 c/µL) During the ST + LT Period		Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Baseline and Changes From Baseline in Absolute Neutrophil Counts (x 10^3 c/µL) During the ST + LT Period		Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Baseline and Changes From Baseline in Absolute Lymphocyte Counts (x 10^3 c/µL) During the ST + LT Period		Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Baseline and Changes From Baseline in Absolute Monocyte Counts (x 10^3 c/µL) During the ST + LT Period		Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period		Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period		Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Changes From Baseline in Systolic Blood Pressure During the ST + LT Period		Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period		Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Changes From Baseline in Heart Rate During the ST + LT Period		Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
Other	Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period	The normality/abnormality of the ECG tracing was determined by the investigator.	Baseline, Weeks 12, 24, 76, 102, 154, 206,
Other	All Reported Hypoglycemic Adverse Events During the ST + LT Treatment Period	Hypoglycemic Events are based upon the Saxagliptin Predefined List of Events, which are hypoglycemia, blood glucose decreased, and hypoglycemic unconsciousness.	AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla
Other	Confirmed Hypoglycemia During the ST + LT Treatment Period	'Confirmed' = recorded on the hypoglycemia AE case report form with a fingerstick glucose <= 50 mg/dL and associated symptoms.	AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla
Primary	Baseline and Change From Baseline in Hemoglobin A1c (A1C) at Week 24	Mean change from baseline is adjusted for baseline value.	Baseline, Week 24
Secondary	Baseline and Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	Mean change from baseline is adjusted for baseline value.	Baseline, Week 24
Secondary	Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24		Week 24
Secondary	Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC)	Mean change from baseline is adjusted for baseline value.	Baseline, Week 24

External Links

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