Efficacy and Safety Study of Saxagliptin + Metformin Immediate Release (IR) Versus Metformin IR Alone in Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Trial to Evaluate the Efficacy and Safety of 2.5 mg Saxagliptin, Twice Daily, in Combination With Metformin IR in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin IR Alone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00885378
• Other study ID #: CV181-080
• Secondary ID: EUDRACT #: 2009-
• Status: Completed
• Phase: Phase 3
• First received: April 21, 2009
• Last updated: May 8, 2015
• Start date: May 2009
• Est. completion date: February 2010

Study information

• Verified date: May 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesGermany: Ethics CommissionHungary: National Institute of PharmacyHungary: Medical Research Council Ethic Committee for Clinical Pharmacology (MRC-ECCP)Mexico: Federal Commission for Sanitary Risks ProtectionMexico: Ethics CommitteeUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the reduction in hemoglobin A1C (A1C) for participants taking saxagliptin in combination with metformin immediate release (IR) versus metformin IR alone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 78 Years

Eligibility

Inclusion Criteria:

• Type 2 diabetes

• 18-78 years of age

• Taking stable twice daily (BID) dosing of metformin IR (at least 1500 mg) for at least 8 weeks

• A1C: 7-10%

• C-peptide: = 0.8 ng/mL

• Body mass index (BMI): =45 kg/m^2

Exclusion Criteria:

• Women of childbearing potential unable or unwilling to use acceptable birth control

• Women who are pregnant or breastfeeding

• Fasting plasma glucose (FPG) >270 mg/dL

• Significant cardiovascular history

• Symptoms of poorly controlled diabetes

• History of diabetic ketoacidosis or hyperosmolar nonketotic coma

• Insulin therapy within one year of screening

• Cardiovascular even within the prior 6 months

• New York Heart Association Stage III/IV congestive heart failure and/or known left ventricular ejection fraction <=40%

• Significant history of renal or hepatic disease

• History of a psychiatric disorder, alcohol or drug abuse within the previous year

• Treatment with potent CYP3A4 inhibitors or inducers

• Immunocompromised participants

• Active liver disease or clinically significant abnormal hepatic, renal , endocrine, metabolic, or hematological screening tests

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Saxagliptin plus metformin IR
Tablets, Oral, 2.5 mg, Twice daily, 12 weeks
• Placebo plus metformin IR
Tablets, Oral, Placebo, Twice daily, 12 weeks

Locations

Country	Name	City	State
Germany	Local Institution	Ludwigshafen
Germany	Local Institution	Magdeberg
Germany	Local Institution	Pirna
Germany	Local Institution	Saarbrucken
Germany	Local Institution	Saarlouis
Germany	Local Institution	Tann
Germany	Local Institution	Wuestensachsen
Hungary	Local Institution	Balatonfured
Hungary	Local Institution	Budapest
Hungary	Local Institution	Eger
Hungary	Local Institution	Szigetvar
Hungary	Local Institution	Zalaegerszeg
Puerto Rico	Local Institution	Ponce
Puerto Rico	Local Institution	San Juan
Puerto Rico	Local Institution	San Juan
Puerto Rico	Local Institution	San Juan
United States	Community Health Care Of Manchester	Akron	Ohio
United States	Central Florida Clinical Trials, Inc.	Altamonte Springs	Florida
United States	Midwest Regional Research, Inc.	Bellbrook	Ohio
United States	Family Care Associates Of Nw Florida	Chipley	Florida
United States	John Muir Physician Network Clinical Research Center	Concord	California
United States	Clinical Therapeutics Corporation	Coral Gables	Florida
United States	Williamette Valley Clinical Studies	Eugene	Oregon
United States	Integrated Medical Group Pc/Fleetwood Clinical Research	Fleetwood	Pennsylvania
United States	Southland Clinical Research Center, Inc.	Fountain Valley	California
United States	Village Family Practice	Houston	Texas
United States	Wells Institute For Health Awareness	Kettering	Ohio
United States	Holston Medical Group	Kingsport	Tennessee
United States	Torrance Clinical Research	Lomita	California
United States	Nextphase Clinical Trials, Inc.	Miami	Florida
United States	Newark Physician Associates	Newark	Ohio
United States	Integris Family Care South	Oklahoma	Oklahoma
United States	Southwest Clinical Research Centers, Llc	Pearland	Texas
United States	Middle Georgia Drug Study Center, Llc	Perry	Georgia
United States	Jackson Clinic	Rolling Fork	Mississippi
United States	Jolene K. Berg, Md., Dgd Research, Inc.	San Antonio	Texas
United States	Ritchken & First M.D.'S	San Diego	California
United States	Louisiana Heart Center Research	Slidell	Louisiana
United States	Southeastern Research Associates, Inc	Taylors	South Carolina
United States	Tidewater Integrated Medical Research	Virginia Beach	Virginia
United States	Integris Family Care Yukon	Yukon	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Germany,  Hungary,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Participant Adverse Event (AE), Related AE, Serious Adverse Event (SAE), Related SAE, and Discontinued Due to AEs Summary	AE = any new untoward medical occurrence/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. Treatment-related=Possible, Probable, or Certain relationship to drug.	Week 1 to Week 12; AEs are included up to the last treatment day + 1 day or the last visit in the double-blind (DB) period. SAEs are included up to the last of 1) the last treatment day + 30 days or 2) the last visit day + 30 days in the DB period.	Yes
Other	Participants With Reported Hypoglycemia AEs During Double-Blind Treatment Period	Hypoglycemic Events are based upon the Saxagliptin Predefined List of Events, which included hypoglycemia, blood glucose decreased, and hypoglycemic unconsciousness.	Week 1 to Week 12; AEs are included up to the last treatment day + 1 day or the last visit in the DB period. SAEs are included up to the last of 1) the last treatment day + 30 days or 2) the last visit day + 30 days in the DB period.	Yes
Other	Participants With Confirmed Hypoglycemia	Confirmed hypoglycemia was defined by a fingerstick glucose value <= 50 mg/dL with associated hypoglycemia symptoms.	Week 1 to Week 12; AEs are included up to the last treatment day + 1 day or the last visit in the DB period. SAEs are included up to the last of 1) the last treatment day + 30 days or 2) the last visit day + 30 days in the DB period.	Yes
Other	Participant Electrocardiogram (ECG) Status at Baseline and Week 12	Abnormal ECGs were defined as those not within the normal limits for the participant, according to the investigator. 'Shifted Normal to Abnormal' and 'Shifted Abnormal to Normal' references a change from measurements at Baseline to those at Week 12.	Baseline, Week 12	Yes
Other	Baseline and Mean Change From Baseline in Participant Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Baseline values reference the measurement for the cohort of participants evaluated at the given time point.	Baseline, Week 4, Week 8, Week 12	Yes
Other	Baseline and Mean Change From Baseline in Participant Heart Rate (HR)	Baseline values reference the measurement for the cohort of participants evaluated at the given time point.	Baseline, Week 4, Week 8, Week 12	Yes
Other	Participants Experiencing Changes From Baseline in Laboratory Parameters That Met the Marked Abnormality Criteria	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. ULN=upper limit of normal; LLN=lower limit of normal.	Baseline, Week 12	Yes
Other	Participants Experiencing Changes From Baseline in Urinalysis Parameters That Met the Marked Abnormality Criteria	Marked abnormality criteria were urine protein: if pre-Rx=o use >=2, if pre-Rx =0.5 or 1 use >=3, if pre-Rx =2, use >=4; urine blood: if pre-Rx=0, use >=2, if pre-Rx=0.5 or 1, use >=3, if pre-Rx=2, use >=4; Urine red blood cell count (RBC): if pre-Rx=o use >=2, if pre-Rx =0.5 or 1 use >=3, if pre-Rx =2, use >=4; urine white blood cell count (WBC): if pre-Rx=o use >=2, if pre-Rx =0.5 or 1 use >=3, if pre-Rx =2, use >=4.	Baseline, Week 12	Yes
Primary	Mean Hemoglobin A1C (A1c) and Change From Baseline to Week 12	Mean change was adjusted for baseline.	Baseline, Week 12	No
Secondary	Mean Baseline and Change From Baseline in Fasting Plasma Glucose (FPG)	Mean change was adjusted for baseline.	Baseline, Week 12	No
Secondary	Percentage of Participants Achieving a Therapeutic Glycemic Response (A1C < 7.0%) at Week 12	Adjusted for baseline. Calculated using the method by Zhang et al. (Zhang M, Tsiatis A, Davidian M. Improving efficiency of inference in randomized clinical trials using auxiliary covariates. Biometrics. Published online on January 11, 2008; Digital Object Identifier: 10.1111/j.1541-0420.2007.00976.x.)	Week 12	No
Secondary	Percentage of Participants Achieving a Therapeutic Glycemic Response (A1C <= 6.5%) at Week 12	Adjusted for baseline. Calculated using the method by Zhang et al. (Zhang M, Tsiatis A, Davidian M. Improving efficiency of inference in randomized clinical trials using auxiliary covariates. Biometrics. Published online on January 11, 2008; Digital Object Identifier: 10.1111/j.1541-0420.2007.00976.x.)	Week 12	No

External Links

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