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

This study has been completed.
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00295633
First received: February 22, 2006
Last updated: June 4, 2014
Last verified: June 2014
  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:


Further study details as provided by AstraZeneca:

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 133 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: June 4, 2014
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
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014