A Study Assessing Saxagliptin Treatment in Type 2 Diabetic Subjects Who Are Not Controlled With TZD Therapy Alone - Full Text View

Purpose

The purpose of this clinical research study is to learn whether Saxagliptin added to thiazolidinedione (TZD) therapy is more effective than TZD alone as a treatment for Type 2 diabetic subjects who are not sufficiently controlled with TZD alone

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: Saxagliptin Drug: Placebo Drug: pioglitazone Drug: rosiglitazone Drug: metformin	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Multicenter, Randomized, Double Blind, Placebo Controlled, Phase III Trial to Evaluate the Efficacy and Safety of Saxagliptin (BMS477118) in Combination With Thiazolidinedione Therapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Thiazolidinedione Therapy Alone

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride Pioglitazone Pioglitazone hydrochloride Rosiglitazone Rosiglitazone Maleate Saxagliptin

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Change From Baseline in Hemoglobin A1c (A1C) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
Mean change from baseline in A1C at Week 24, adjusted for baseline value.

Secondary Outcome Measures:

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
Mean change from baseline in FPG at Week 24, adjusted for baseline value.
Percentage of Participants Achieving A1c <7% at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Percentage of participants achieving A1C < 7%, the American Diabetic Association's defined goal for glycemia, at each dose of saxagliptin plus TZD versus placebo plus TZD at Week 24.
Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
Mean change from baseline for 0 to 180 minutes PPG AUC achieved at each dose of saxagliptin plus TZD versus placebo plus TZD at Week 24, adjusted for baseline value.

Enrollment:	565
Study Start Date:	March 2006
Study Completion Date:	October 2008
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Saxagliptin plus open-label TZD (A) Saxagliptin PLUS pioglitazone OR rosiglitazone PLUS open-label metformin (as needed as rescue medication)	Drug: Saxagliptin Tablets, Oral, 2.5 mg, Once daily (6 months ST, 12 months LT) Other Name: BMS-477118 Drug: pioglitazone Tablets, Oral, 30 mg or 45 mg, once daily (6 months ST, 12 months LT) Drug: rosiglitazone Tablets, Oral, 4 mg, once daily or 8 mg, either as once or twice daily (6 months ST, 12 months LT) Drug: metformin Tablets, Oral, 500-2500 mg, as needed (12 months LT)
Experimental: Saxagliptin plus open-label TZD (B) Saxagliptin PLUS pioglitazone OR rosiglitazone PLUS open-label metformin (as needed as rescue medication)	Drug: Saxagliptin Tablets, Oral, 5 mg, once daily (6 months ST, 12 months LT) Other Name: BMS-477118 Drug: pioglitazone Tablets, Oral, 30 mg or 45 mg, once daily (6 months ST, 12 months LT) Drug: rosiglitazone Tablets, Oral, 4 mg, once daily or 8 mg, either as once or twice daily (6 months ST, 12 months LT) Drug: metformin Tablets, Oral, 500-2500 mg, as needed (12 months LT)
Placebo Comparator: Placebo plus open-label TZD (C) Placebo PLUS pioglitazone OR rosiglitazone PLUS open-label metformin (as needed as rescue medication)	Drug: Placebo Tablets, Oral, 0 mg, Once daily (6 months ST, 12 months LT) Drug: pioglitazone Tablets, Oral, 30 mg or 45 mg, once daily (6 months ST, 12 months LT) Drug: rosiglitazone Tablets, Oral, 4 mg, once daily or 8 mg, either as once or twice daily (6 months ST, 12 months LT) Drug: metformin Tablets, Oral, 500-2500 mg, as needed (12 months LT)

Detailed 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 (defined as rescue medication) added onto their blinded study medication

Eligibility

Ages Eligible for Study:	18 Years to 77 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Type 2 diabetics currently receiving a stable dose of TZD monotherapy (pioglitazone 30mg or 45mg, or rosiglitazone 4mg or 8mg) for at least 12 weeks prior to screening.
Hemoglobin A1c (HbA1c) > = 7.0% and < = 10.5%
Body mass index < = 45kg/m2
Fasting C-peptide > = 1 ng/mL

Exclusion Criteria:

Symptomatic poorly controlled diabetes
Recent cardiac or cerebrovascular event
Serum creatinine > = 2.0 mg/dL

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00295633

Show 133 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trials Disclosure This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

Publications:

Hollander P, Li J, Allen E, Chen R; CV181-013 Investigators. Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone. J Clin Endocrinol Metab. 2009 Dec;94(12):4810-9. Epub 2009 Oct 28.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Karyekar C, Donovan M, Allen E, Fleming D, Ravichandran S, Chen R. Efficacy and safety of saxagliptin combination therapy in US patients with type 2 diabetes. Postgrad Med. 2011 Jul;123(4):63-70.

Hollander PL, Li J, Frederich R, Allen E, Chen R; CV181013 Investigators. Safety and efficacy of saxagliptin added to thiazolidinedione over 76 weeks in patients with type 2 diabetes mellitus. Diab Vasc Dis Res. 2011 Apr;8(2):125-35.

Responsible Party:	Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00295633 History of Changes
Other Study ID Numbers:	CV181-013
Study First Received:	February 22, 2006
Results First Received:	August 17, 2009
Last Updated:	August 4, 2010
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Rosiglitazone
Saxagliptin

Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013