Saxagliptin Treatment in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin (BMS-477118) as Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00121641
• Other study ID #: CV181-011
• Status: Completed
• Phase: Phase 3
• First received: July 15, 2005
• Last updated: March 16, 2015
• Start date: July 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 (BMS-477118) is more effective than placebo as a treatment for type 2 diabetic subjects who are not sufficiently controlled with diet and exercise

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 metformin added onto their blinded study medication. Subjects with screening hemoglobin A1c (A1C) > 10.0% and ≤ 12.0%, who otherwise meet all inclusion/exclusion criteria, were eligible to enroll directly into Open-Label Treatment Cohort (Direct Enrollees) and receive open-label saxagliptin 10 mg. Those who completed the short-term period were eligible to enter into the long-term treatment extension period.Saxagliptin dose titration was not permitted.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1035
• Est. completion date: February 2010
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 77 Years

Eligibility

Inclusion Criteria:

• Type 2 diabetes mellitus

• Drug naive

• Hemoglobin (Hb) A1c >= 7.0% and <= 10.0% (>10% and <= 12% for open label arm)

• Fasting C-peptide >= 1 ng/mL

• Body mass index <= 40 kg/m2

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 Women of Child Bearing Potential

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Saxagliptin
Tablets, Oral, 2.5 mg, Once daily (24 weeks short term [ST], 42 months long term [LT])
• Saxagliptin
Tablets, Oral, 5 mg, Once daily (24 weeks ST, 42 months LT)
• Saxagliptin
Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT)
• Placebo matching Saxagliptin
Tablets, Oral, 0mg, Once daily (24 weeks ST, 42 months LT)
• Metformin
Tablets, Oral, 500 mg, daily (42 months LT)
• Placebo matching Metformin
Tablets, Oral, 0 mg, daily (42 months LT)
• Saxagliptin
Tablets, Oral, 10 mg, Once daily (24 weeks ST, 42 months LT) Open Label
• Metformin
Tablets, Oral, 500-2000 mg (as needed for rescue)

Locations

Country	Name	City	State
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
Canada	Local Institution	Bathurst	New Brunswick
Canada	Local Institution	Calgary	Alberta
Canada	Local Institution	Charlottetown	Prince Edward Island
Canada	Local Institution	Drummondville	Quebec
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Fleurimont	Quebec
Canada	Local Institution	Gatineau	Quebec
Canada	Local Institution	Granby	Quebec
Canada	Local Institution	Kelowna	British Columbia
Canada	Local Institution	Longueuil	Quebec
Canada	Local Institution	Manuels	Newfoundland and Labrador
Canada	Local Institution	Moncton	New Brunswick
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Mount Pearl	Newfoundland and Labrador
Canada	Local Institution	Newmarket	Ontario
Canada	Local Institution	Oakville	Ontario
Canada	Local Institution	Peterborough	Ontario
Canada	Local Institution	Portage La Prairie	Manitoba
Canada	Local Institution	Quesnel	British Columbia
Canada	Local Institution	Sarnia	Ontario
Canada	Local Institution	Saskatoon	Saskatchewan
Canada	Local Institution	St. John's	Newfoundland and Labrador
Canada	Local Institution	St. Leonard	Quebec
Canada	Local Institution	Ste-Foy	Quebec
Canada	Local Institution	Strathroy	Ontario
Canada	Local Institution	Thornhill	Ontario
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Vancouver	British Columbia
Canada	Local Institution	Winnipeg	Manitoba
Mexico	Local Institution	Aguascalientes
Mexico	Local Institution	Durango
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Hermosillo	Sonora
Mexico	Local Institution	Mexico City	Distrito Federal
Mexico	Local Institution	Mexico D.F.	Distrito Federal
Mexico	Local Institution	Monterrey	Nuevo Leon
Puerto Rico	Local Institution	Carolina
Puerto Rico	Local Institution	Guaynabo
Puerto Rico	Local Institution	Ponce
Puerto Rico	Local Institution	Rio Piedras
Puerto Rico	Local Institution	San Juan
Taiwan	Local Institution	Hualien
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taipei
United States	Local Institution	Altamonte Springs	Florida
United States	Local Institution	Anaheim	California
United States	Local Institution	Anniston	Alabama
United States	Local Institution	Athens	Ohio
United States	Local Institution	Ayer	Massachusetts
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	Castle Rock	Colorado
United States	Local Institution	Charleston	South Carolina
United States	Local Institution	Chester	Maryland
United States	Local Institution	Chipley	Florida
United States	Local Institution	Cocoa Beach	Florida
United States	Local Institution	Cooperstown	New York
United States	Local Institution	Coral Gables	Florida
United States	Local Institution	Dallas	Texas
United States	Local Institution	Denver	Colorado
United States	Local Institution	Dubuque	Iowa
United States	Local Institution	Fleetwood	Pennsylvania
United States	Local Institution	Fort Lauderdale	Florida
United States	Local Institution	Fort Worth	Texas
United States	Local Institution	Fountain Valley	California
United States	Local Institution	Franklin	Ohio
United States	Local Institution	Fresno	California
United States	Local Institution	Greensboro	North Carolina
United States	Local Institution	Houston	Texas
United States	Local Institution	Huntersville	North Carolina
United States	Local Institution	Iowa City	Iowa
United States	Local Institution	Jonesboro	Arizona
United States	Local Institution	Jupiter	Florida
United States	Local Institution	Kalispell	Montana
United States	Local Institution	Kansas City	Missouri
United States	Local Institution	Kissimmee	Florida
United States	Local Institution	Las Vegas	Nevada
United States	Local Institution	Lexington	Kentucky
United States	Local Institution	Little Rock	Arkansas
United States	Local Institution	Long Beach	California
United States	Local Institution	Los Angeles	California
United States	Local Institution	Loveland	Colorado
United States	Local Institution	Marianna	Florida
United States	Local Institution	Mesa	Arizona
United States	Local Institution	Middletown	New Jersey
United States	Local Institution	Morristown	Tennessee
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	Pheonix	Arizona
United States	Local Institution	Philadelphia	Pennsylvania
United States	Local Institution	Pittsburgh	Pennsylvania
United States	Local Institution	Portland	Oregon
United States	Local Institution	Prince Frederick	Maryland
United States	Local Institution	Rolling Fork	Mississippi
United States	Local Institution	Rolling Hills Estates	California
United States	Local Institution	Sacramento	California
United States	Local Institution	Salt Lake City	Utah
United States	Local Institution	San Antonio	Texas
United States	Local Institution	Santa Ana	California
United States	Local Institution	Sparta	North Carolina
United States	Local Institution	Spring Valley	California
United States	Local Institution	Springfield	Missouri
United States	Local Institution	St. Louis	Missouri
United States	Local Institution	Statesville	North Carolina
United States	Local Institution	Temple	Texas
United States	Local Institution	Texarkana	Texas
United States	Local Institution	The Colony	Texas
United States	Local Institution	Toms River	New Jersey
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	West Palm Beach	Florida
United States	Local Institution	Wichita	Kansas
United States	Local Institution	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Mexico,  Puerto Rico,  Taiwan, 

References & Publications (1)

Rosenstock J, Aguilar-Salinas C, Klein E, Nepal S, List J, Chen R; CV181-011 Study Investigators. Effect of saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes. Curr Med Res Opin. 2009 Oct;25(10):2401-11. doi: 10.1185/03007990903178735. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Baseline Demographic Characteristic (Age, Continuous) - Summary for ST + LT Treatment Period - Open-Label Cohort	This cohort represents a different population (screening A1C > 10.0% and = 12.0%) than the double-blind cohort, and was presented separately in the study report.	Baseline
Other	Baseline Demographic Characteristics - Summary for ST + LT Treatment Period - Open-Label Cohort	This cohort represents a different population (screening A1C > 10.0% and = 12.0%) than the double-blind cohort, and was presented separately in the study report.	Baseline
Other	Baseline Demographic Characteristic (Weight) - Summary for ST + LT Treatment Period - Open-Label Cohort	This cohort represents a different population (screening A1C > 10.0% and = 12.0%) than the double-blind cohort, and was presented separately in the study report.	Baseline
Other	Baseline Demographic Characteristic (Body Mass Index) - Summary for ST + LT Treatment Period - Open-Label Cohort	This cohort represents a different population (screening A1C > 10.0% and = 12.0%) than the double-blind cohort, and was presented separately in the study report.	Baseline
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; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 109 weeks in 10 mg arm, 94.7 weeks in 2.5 mg arm, 103 weeks in 5 mg arm, and 98.4 weeks in placebo arm.
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 was 109 weeks in 10 mg arm, 94.7 weeks in 2.5 mg arm, 103 weeks in 5 mg arm, and 98.4 weeks in placebo arm.
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		Baseline, 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		Baseline, 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		Baseline, 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	Overall Summary of Adverse Events During ST+LT Treatment Period - Open-Label Cohort	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; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 34 weeks.
Other	Marked Laboratory Abnormalities During ST + LT Treatment Period - Open-Label Cohort	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 was 34 weeks.
Other	All Reported Hypoglycemic Adverse Events During ST + LT Treatment Period	Hypoglycemic Events are based upon the Saxagliptin Predefined List of Events, which included hypoglycemia, blood glucose decreased, and hypoglycemic unconsciousness.	AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 109 weeks in 10 mg arm, 94.7 weeks in 2.5 mg arm, 103 weeks in 5 mg arm, and 98.4 weeks in placebo arm.
Other	Confirmed Hypoglycemia During ST + LT Treatment Period	'Confirmed' = recorded on the hypoglycemia AE case report form page with a fingerstick glucose <= 50 mg/dL and associated symptoms	AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 109 weeks in 10 mg arm, 94.7 weeks in 2.5 mg arm, 103 weeks in 5 mg arm, and 98.4 weeks in placebo arm.
Other	All Reported Hypoglycemic Adverse Events During ST + LT Treatment Period - Open-Label Cohort	Hypoglycemic Events are based upon the Saxagliptin Predefined List of Events, which included hypoglycemia, blood glucose decreased, and hypoglycemic unconsciousness.	AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 34 weeks.
Other	Confirmed Hypoglycemia During ST + LT Treatment Period - Open-Label Cohort	'Confirmed' = recorded on the hypoglycemia AE case report form page with a fingerstick glucose <= 50 mg/dL and associated symptoms	AEs: up to last treatment day + 1 day or last visit; SAEs: up to last treatment day + 30 days or last visit + 30 days. Mean duration of exposure was 34 weeks.
Other	Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period - Open Label Cohort	The normality/abnormality of the ECG tracing was determined by the investigator.	Baseline, Weeks 12, 24, 76, 102, 154, 206
Other	Changes From Baseline in Systolic Blood Pressure During the ST + LT Period - Open Label Cohort		Baseline, 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
Other	Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period - Open Label Cohort		Baseline, 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
Other	Changes From Baseline in Heart Rate During the ST + LT Period - Open Label Cohort		Baseline, 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
Primary	Hemoglobin A1c (A1C) Changes From Baseline at Week 24	To compare the change from baseline in HbA1c achieved with each dose of saxagliptin versus placebo in treatment naive subjects with type 2 diabetes who have inadequate glycemic control defined as A1C =7.0% and =10.0%.	Baseline, Week 24
Primary	A1C Changes From Baseline at Week 24 - Open Label Cohort	To compare the change from baseline in HbA1c achieved with each dose of saxagliptin versus placebo in treatment naive subjects with type 2 diabetes who have inadequate glycemic control defined as A1C =7.0% and =10.0%.	Baseline, Week 24
Secondary	Baseline and Change From Baseline at Week 24 in Fasting Plasma Glucose (FPG)		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)		Baseline, Week 24
Secondary	Baseline and Change From Baseline at Week 24 in Fasting Plasma Glucose (FPG) - Open Label Cohort		Baseline, Week 24
Secondary	Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24 - Open Label Cohort		Week 24
Secondary	Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC) - Open Label Cohort		Baseline, Week 24

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