A Phase 3 Study of BMS-477118 in Combination With Metformin in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise - Full Text View

Sponsor:	Bristol-Myers Squibb
Information provided by:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00327015

Purpose

The purpose of this trial is to understand if adding saxagliptin to metformin therapy is safe and works better than taking either saxagliptin or metformin alone

Condition	Intervention	Phase
Diabetes	Drug: Saxagliptin Drug: Metformin Drug: Placebo Drug: pioglitazone	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Multicenter, Randomized, Double-Blind Active-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination With Metformin IR as Initial Therapy Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride Pioglitazone Pioglitazone hydrochloride 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, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
Mean change from baseline in A1C at Week 24, adjusted for baseline value.
Change From Baseline in A1C at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy [ 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, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
Mean change from baseline in FPG at Week 24, adjusted for baseline value.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy [ 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, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Percentage of participants achieving A1C < 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24.
Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Percentage of participants achieving A1C < 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus metformin versus metformin alone 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, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjusted for baseline value.
Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjsuted for baseline value.
Percentage of Participants Achieving A1C ≤6.5% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Percentage of participants achieving A1C ≤6.5%, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24.
Percentage of Participants Achieving A1C ≤6.5% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Percentage of participants achieving A1C ≤6.5%, at each dose of saxagliptin plus metformin versus metformin alone at Week 24.
Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus saxagliptin alone.
Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus metformin alone.

Enrollment:	1306
Study Start Date:	May 2006
Study Completion Date:	December 2008
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Saxagliptin and Metformin (A) PLUS open-label pioglitazone (as needed as rescue medication)	Drug: Saxagliptin Coated Tablets, Oral, 10 mg, Daily (6 months ST, 12 months LT) Other Name: BMS-477118 Drug: Metformin Coated tablets, Oral, 500 mg, Daily (6 months ST, 12 months LT) Drug: pioglitazone Tablets, Oral, 15-45 mg, as needed (12 months LT)
Experimental: Saxagliptin and Metformin (B) PLUS open-label pioglitazone (as needed as rescue medication)	Drug: Saxagliptin Coated tablets, PO, 5 mg, Daily (6 months ST, 12 months LT) Other Name: BMS-477118 Drug: Metformin Coated tablets, Oral, 500 mg, Daily (6 months ST, 12 months LT) Drug: pioglitazone Tablets, Oral, 15-45 mg, as needed (12 months LT)
Experimental: Saxagliptin and Placebo (C) PLUS open-label pioglitazone (as needed as rescue medication)	Drug: Saxagliptin Coated Tablets, Oral, 10 mg, Daily (6 months ST, 12 months LT) Other Name: BMS-477118 Drug: Placebo Coated tablets, Oral, 0 mg, Daily (6 months ST, 12 months LT) Drug: pioglitazone Tablets, Oral, 15-45 mg, as needed (12 months LT)
Active Comparator: Metformin and Placebo (D) PLUS open-label pioglitazone (as needed as rescue medication)	Drug: Metformin Coated tablets, Oral, 500 mg, Daily (6 months ST, 12 months LT) Drug: Placebo Coated tablets, Oral, 0 mg, Daily (6 months ST, 12 months LT) Drug: pioglitazone Tablets, Oral, 15-45 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 pioglitazone (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 diabetes
Inadequate blood sugar control
No current treatment with other medications to lower blood sugar

Exclusion Criteria:

Major heart, liver or kidney problems
Pregnant or breast feeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00327015

Show 211 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:

Jadzinsky M, Pfützner A, Paz-Pacheco E, Xu Z, Allen E, Chen R; CV181-039 Investigators. Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab. 2009 Jun;11(6):611-22.

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

Pfützner A, Paz-Pacheco E, Allen E, Frederich R, Chen R; CV181039 Investigators. Initial combination therapy with saxagliptin and metformin provides sustained glycaemic control and is well tolerated for up to 76 weeks. Diabetes Obes Metab. 2011 Jun;13(6):567-76.

Responsible Party:	Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00327015 History of Changes
Other Study ID Numbers:	CV181-039
Study First Received:	May 15, 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
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 24, 2012