Study To Evaluate 24 Hour Blood Sugar Control (24-hour Mean Weighted Glucose) In Subjects That Are Taking Saxagliptin 5 mg Added Onto Metformin XR 1500 XR mg Compared To Subjects Taking Metformin XR 1500 mg Up-titrated To Metformin XR 2000 mg

Type 2 Diabetes Clinical Trial

Official title:

A 4-Week, Multicenter, Randomized, Double-Blind, Phase 3b Trial to Evaluate the Efficacy of Saxagliptin in Combination With Metformin XR 1500 mg Versus Up-titrated Metformin XR to 2000 mg in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise and a Stable Dose of Metformin XR 1500 mg

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00918138
• Other study ID #: CV181-085
• Status: Completed
• Phase: Phase 3
• First received: June 9, 2009
• Last updated: May 4, 2015
• Start date: August 2009
• Est. completion date: May 2010

Study information

• Verified date: May 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationIsrael: Ministry of HealthMexico: Federal Commission for Sanitary Risks ProtectionMexico: Ethics CommitteeArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to compare effect of Saxagliptin as add-on to Metformin on 24-hour mean weighted glucose (MWG) to the effect of uptitrating Metformin in subjects with T2DM inadequately controlled on metformin alone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 219
• Est. completion date: May 2010
• Est. primary completion date: May 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 dose of metformin immediate release (IR) or XR =850 mg and =1500 mg as monotherapy for at least 8 weeks prior to screening

• Glycosylated hemoglobin A1C (A1C) 7.5-11.5% at screening

• Fasting C-peptide: =1.0 ng/mL

• FPG=126 mg/dl obtained at the Day -7 visit

• Body mass index (BMI): = 40kg/m²

• A1C = 7.0% and = 11.0% obtained at the Day -7 visit for randomization

Exclusion Criteria:

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

• Women who are pregnant or breastfeeding

• Significant cardiovascular history

• Active liver disease

• Renal impairment

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, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Saxagliptin
Tablets, Oral, 5 mg, once daily, 4 weeks
• Metformin XR
Tablets, Oral, 1500 mg, once daily, 4 weeks
• Placebo matching Metformin XR
Tablets, Oral, 0 mg, once daily, 4 weeks
• Metformin XR
Tablets, Oral, 500 mg, once daily, 4 weeks
• Placebo matching Saxagliptin
Tablets, Oral, 0 mg, once daily, 4 weeks

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Israel	Local Institution	Beer-Sheva
Israel	Local Institution	Holon
Israel	Local Institution	Kfar-Saba
Israel	Local Institution	Zefat
Mexico	Local Institution	Durango
Mexico	Local Institution	Durango
Mexico	Local Institution	Monterrey	Nuevo Leon
United States	River Birch Research Alliance, Llc	Blue Ridge	Georgia
United States	Medpace Clinical Pharmacology Unit	Cincinnati	Ohio
United States	Clinical Research Of South Florida	Coral Gables	Florida
United States	Palm Springs Research Institute	Hialeah	Florida
United States	Jasper Clinic, Inc.	Kalamazoo	Michigan
United States	Clinilabs, Inc.	New York	New York
United States	Healthcare Clinical Data, Inc.	North Miami	Florida
United States	Dedicated Phase I, Inc.	Phoenix	Arizona
United States	Pacific Sleep Medicine Services (Avastra Clinical Trials)	Redlands	California
United States	Clinical Trials Of Texas Inc.	San Antonio	Texas
United States	Orange County Research Center	Tustin	California
United States	Advanced Clinical Research	West Jordan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Israel,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Participants With Confirmed Hypoglycemia Events During the Treatment Period	'Confirmed' = recorded on the hypoglycemia AE case report form with a fingerstick for glucose <= 50 mg/dL and associated symptoms.	AEs: up to last treatment day (LTD) +1 day or last visit day (LVD), whichever came last ; SAEs: up to LTD +30 days or LVD + 30 days, whichever came last. Mean duration of exposure=27.7 days for Saxa 5 mg + Met XR 1500 mg, and 28.3 days for Met 2000 mg.	Yes
Other	Participants With Reported Hypoglycemic Adverse Events During Treatment Period	Hypoglycemic events are based upon the Saxagliptin Predefined List of Events, which includes hypoglycemia, blood glucose decreased, and hypoglycemic unconsciousness. The Hypoglycemic events occurred in less than 5% of the participants and hence do not appear in the adverse events module.	AEs: up to last treatment day (LTD) +1 day or last visit day (LVD), whichever came last ; SAEs: up to LTD +30 days or LVD + 30 days, whichever came last. Mean duration of exposure=27.7 days for Saxa 5 mg + Met XR 1500 mg, and 28.3 days for Met 2000 mg.	Yes
Primary	Change From Baseline in 24-Hour Mean Weighted Glucose (MWG) at Week 4	Adjusted mean change from baseline in MWG achieved with saxagliptin 5 mg plus metformin XR versus placebo plus metformin XR at Week 24. MWG was calculated as the area under the curve (AUC) for the full 24 hours expressed as average mg/dL. Glucose measurements were collected 30 minutes before and just prior to each meal (0 minutes) and 30, 60, 120, and 180 minutes after each meal (with 1 additional measurement at 240 minutes after the evening meal), midnight, 3 AM, and at end-of-domicile visit 24 hours after the first measurement. Mean change from baseline was adjusted for baseline value.	Baseline, Week 4	No
Secondary	Change From Baseline to Week 4 in 2-hour Postprandial Glucose (PPG) (2 Hours After the Evening Meal)	Adjusted mean change from baseline in 2-hour postprandial (after mealtime) plasma glucose two hours after start of the evening meal during 24-hour domicile visits evaluated both at pre-randomization (baseline) and at Week 4. Mean change from baseline was adjusted for baseline value.	Baseline, Week 4	No
Secondary	Change From Baseline Fasting Plasma Glucose (FPG) at Week 4, Obtained Immediately Before the Morning Meal	FPG measurements were done at baseline, day 14 and 28. At baseline and day 28, the FPG value=plasma glucose value collected 30 minutes prior to the morning meal during the domicile visit.	Baseline, Week 4	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