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

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

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

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Saxagliptin; Drug: Saxagliptin; Drug: pioglitazone; Drug: rosiglitazone; Drug: metformin; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 565
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425AGC
    • Local Institution
  • Buenos Aires, Argentina, C1408INH
    • Local Institution
  • Buenos Aires
    • Belgrano, Buenos Aires, Argentina, C1426EGP
      • Local Institution
    • Chacabuco, Buenos Aires, Argentina, B6740CWC
      • Local Institution
    • Ciudad Auton., Buenos Aires, Argentina, C1505CWB
      • Local Institution
    • La Plata, Buenos Aires, Argentina, 1900
      • Local Institution
    • Moron, Buenos Aires, Argentina, B17081FF
      • Local Institution
  • Mendoza
    • Ciudad De Mendoza, Mendoza, Argentina, M5519XAC
      • Local Institution
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000CVD
      • Local Institution
  • Tucuman
    • Lanus Este, Tucuman, Argentina, 1824
      • Local Institution
• Canada
  • Newfoundland and Labrador
    • St. Johns, Newfoundland and Labrador, Canada, A1E 2C2
      • Local Institution
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Local Institution
  • Ontario
    • Sarnia, Ontario, Canada, N7T 4X3
      • Local Institution
    • St Catharines, Ontario, Canada, L2R 7P3
      • Local Institution
  • Quebec
    • St-Leonard, Quebec, Canada, H1S 3A9
      • Local Institution
    • Ste-Foy, Quebec, Canada, G1V 4G2
      • Local Institution
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 3H3
      • Local Institution
• India
  • Bangalore, India, 560054
    • Local Institution
  • Bangalore, India, 560010
    • Local Institution
  • Chennai, India, 680004
    • Local Institution
  • Chennai, India, 600010
    • Local Institution
  • Chennai, India, 600013
    • Local Institution
  • Chennai, India, 600086
    • Local Institution
  • Hariyana, India, 132001
    • Local Institution
  • Hyderabad, India, 500082
    • Local Institution
  • Indore, India, 452001
    • Local Institution
  • Maharashtra, India, 411011
    • Local Institution
  • Mangalore, India, 575001
    • Local Institution
  • Mumbai, India, 400021
    • Local Institution
  • Mumbai, India, 400067
    • Local Institution
  • Pune, India, 411011
    • Local Institution
  • Vellore, India, 632004
    • Local Institution
• Mexico
  • Aguascalientes, Mexico, 20232
    • Local Institution
  • Chihuahua
    • Chichuahua, Chihuahua, Mexico, 31000
      • Local Institution
  • Distrito Federal
    • Angeles Del Pedregal, Distrito Federal, Mexico, 10700
      • Local Institution
  • Jalisco
    • Zapopan, Jalisco, Mexico, 45200
      • Local Institution
  • Morelos
    • Michoacan, Morelos, Mexico, 58000
      • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 66260
      • Local Institution
• Peru
  • Lima
    • Cercado De Lima, Lima, Peru, 1
      • Local Institution
    • La Victoria, Lima, Peru, 13
      • Local Institution
    • Miraflores, Lima, Peru, 18
      • Local Institution
    • San Isidro, Lima, Peru, 27
      • Local Institution
    • San Martin De Porres, Lima, Peru, 31
      • Local Institution
    • Santiago De Surco, Lima, Peru, 33
      • Local Institution
• Philippines
  • Cebu City, Philippines, 6000
    • Local Institution
  • Cebu City, Philippines, 1600
    • Local Institution
  • Iloilo City, Philippines, 5000
    • Local Institution
  • Las Pinas, Philippines, 1740
    • Local Institution
  • Pasig City, Philippines, 1600
    • Local Institution
• Puerto Rico
  • Carolina, Puerto Rico, 00983
    • Local Institution
  • Ponce, Puerto Rico, 00716
    • Local Institution
  • Ponce, Puerto Rico, 00717
    • Local Institution
  • Rio Piedras, Puerto Rico, 00926
    • Local Institution
  • San Juan, Puerto Rico, 00920
    • Local Institution
• United States
  • Alabama
    • Haleyville, Alabama, United States, 35565
      • Winston Technology, Inc.
    • Mobile, Alabama, United States, 36606
      • Sunbelt Research Group, Llc
    • Ozark, Alabama, United States, 36360
      • Iicr, Inc.
  • Arizona
    • Mesa, Arizona, United States, 85213
      • Clinical Research Advantage, Inc
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Clinic
    • Little Rock, Arkansas, United States, 72205
      • Little Rock Family Practice Clinic
  • California
    • Beverly Hills, California, United States, 90211
      • Impact Clinical Trials
    • Beverly Hills, California, United States, 90211
      • Lovelace Scientific Resources, Inc.
    • Encino, California, United States, 91436
      • Medical Group of Encino
    • Greenbrae, California, United States, 94904
      • Marin Endocrine Care And Research, Inc.
    • Huntington Park, California, United States, 90255
      • Del Rosario Medical Clinic, Inc.
    • Loma Linda, California, United States, 92357
      • Loma Linda Va Healthcare Systems
    • Los Angeles, California, United States, 90025
      • Peak Health Medical Group
    • Los Gatos, California, United States, 95032
      • Richard Cherlin, Md
    • Mission Viejo, California, United States, 92691
      • Mission Internal Medical Group
    • Palm Desert, California, United States, 92260
      • Desert Medical Advances
  • Colorado
    • Denver, Colorado, United States, 80209
      • Denver Internal Medicine Group
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Stamford Therapeutics Consortium
    • Waterbury, Connecticut, United States, 06708
      • Phoenix Internal Medicine Associates, Llc
  • Florida
    • Altamonte Springs, Florida, United States, 32714
      • Central Florida Clinical Trials, Inc.
    • Chipley, Florida, United States, 32428
      • Southern Family Healthcare, Pa
    • Defuniak Springs, Florida, United States, 32435
      • Doctors Medical center of Walton County
    • Hollywood, Florida, United States, 33021
      • Horizon Institute for Clinical Research
    • Jacksonville, Florida, United States, 32205
      • Jacksonville Center for Clinical Research
    • Marianna, Florida, United States, 32446
      • Panhandle Family Care Associates
    • Miami, Florida, United States, 33156
      • Baptist Diabetes Associates
    • Miami, Florida, United States, 33145
      • Nextphase Clinical Trials, Inc
    • Sarasota, Florida, United States, 34239
      • Heart & Vascular Center Research, Inc.
  • Georgia
    • Dunwoody, Georgia, United States, 30338
      • Alan B. Miller, Md
    • Marietta, Georgia, United States, 30060
      • Marietta Clinical Research, Inc.
    • Roswell, Georgia, United States, 30076
      • Endocrine Research Solutions, Inc.
  • Hawaii
    • Kahului, Hawaii, United States, 96732
      • D. Thomas Rogers, Md, Facs
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Southeast Idaho Family Practice
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar-Crosse Research Center
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Physicians Research Group
    • Valparaiso, Indiana, United States, 46383
      • Northwest Indiana Center for Clinical Research
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Lipid Research Clinic
  • Kansas
    • Wichita, Kansas, United States, 67203
      • Professional Research Network of Kansas
  • Louisiana
    • West Monroe, Louisiana, United States, 71291
      • Mouhaffel, Assad H.
  • Michigan
    • Portage, Michigan, United States, 49024
      • Promed Physicians Family Practice
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
      • Olive Branch Family Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89146
      • Radiant Research Las Vegas
    • North Las Vegas, Nevada, United States, 89030
      • Nevada Alliance Against Diabetes
  • New Jersey
    • Holmdel, New Jersey, United States, 07733
      • Office Of Ammar Bazerbashi, Md
    • South Bound Brook, New Jersey, United States, 08880
      • Urgentmed, P.C.
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Medical Research Associates Of Charlotte, Inc.
    • Statesville, North Carolina, United States, 28625
      • Carolina Pharmaceutical Research
  • Ohio
    • Canal Fulton, Ohio, United States, 44614
      • Community Health Care
    • Canton, Ohio, United States, 44718
      • Clinical Research Limited
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research, Inc.
    • Dayton, Ohio, United States, 45439
      • Providence Health Partners - Center For Clinical Research
    • Gallipolis, Ohio, United States, 45631
      • Holzer Clinic
    • Kettering, Ohio, United States, 45429
      • Wells Institute for Health Awareness
  • Oregon
    • Eugene, Oregon, United States, 97401
      • David Witkin, Md
  • Pennsylvania
    • Harleysville, Pennsylvania, United States, 19438
      • Harleysville Medical Associates
    • Levittown, Pennsylvania, United States, 19056
      • Family Medical Associates
    • Pittsburgh, Pennsylvania, United States, 15216
      • Banksville Medical Pc
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Three Rivers Medical Associates, Pa
    • Greer, South Carolina, United States, 29651
      • Radiant Research, Greer
    • Simpsonville, South Carolina, United States, 29681
      • Upstate Pharmaceutical Research
  • Tennessee
    • Alcoa, Tennessee, United States, 37701
      • East Tennessee Medical Group
    • Morristown, Tennessee, United States, 37813
      • Healthstar Physicians
    • Nashville, Tennessee, United States, 37209
      • Hayes Endocrine And Diabetes Center
  • Texas
    • Austin, Texas, United States, 78705
      • Capital Medical Clinic, Llp
    • Austin, Texas, United States, 78731
      • Texas Diabetes and Endocrinology, P.A.
    • Austin, Texas, United States, 78752
      • Radiant Research-Austin
    • Dallas, Texas, United States, 75246
      • Priscilla Hollander, Md, Phd
    • Fort Worth, Texas, United States, 76104
      • The Medical Group Of Texas
    • Houston, Texas, United States, 77024
      • Mobley Research Center
    • Houston, Texas, United States, 77074
      • Family Physician, Pa
    • Houston, Texas, United States, 77081
      • Mapleridge Medical Center
    • Midland, Texas, United States, 79705
      • Diabetes Center of the Southwest
    • Pearland, Texas, United States, 77584
      • Pearland Primary Care Associates, Llp
    • Rosenberg, Texas, United States, 77471
      • Med-Cure
    • San Antonio, Texas, United States, 78229
      • S.A.M. Clinical Research Center
    • San Antonio, Texas, United States, 78229
      • Radiant Research San Antonio
    • Texarkana, Texas, United States, 75503
      • Collom And Carney Clinic
  • Virginia
    • Richmond, Virginia, United States, 23294
      • National Clinical Research, Inc.
    • Virginia Beach, Virginia, United States, 23451
      • Tidewater Integrated Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: BMS-477118; Drug: Saxagliptin; Tablets, Oral, 5 mg, once daily (6 months ST, 12 months LT); Other Names: 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, 2.5 mg, Once daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Tablets, Oral, 5 mg, once daily (6 months ST, 12 months LT); Other Names: 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: 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); Drug: Placebo; Tablets, Oral, 0 mg, Once daily (6 months ST, 12 months LT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (A1C) at Week 24	Mean change from baseline in A1C at Week 24, adjusted for baseline value.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	Mean change from baseline in FPG at Week 24, adjusted for baseline value.	Baseline, Week 24
Percentage of Participants Achieving A1c <7% at Week 24	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.	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	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.	Baseline, Week 24

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Perl S, Cook W, Wei C, Iqbal N, Hirshberg B. Saxagliptin Efficacy and Safety in Patients With Type 2 Diabetes and Moderate Renal Impairment. Diabetes Ther. 2016 Sep;7(3):527-35. doi: 10.1007/s13300-016-0184-9. Epub 2016 Jul 11.
• Bonora E, Bryzinski B, Hirshberg B, Cook W. A post hoc analysis of saxagliptin efficacy and safety in patients with type 2 diabetes stratified by UKPDS 10-year cardiovascular risk score. Nutr Metab Cardiovasc Dis. 2016 May;26(5):374-9. doi: 10.1016/j.numecd.2015.11.004. Epub 2015 Dec 1.
• Karyekar CS, Frederich R, Ravichandran S. Clinically relevant reductions in HbA1c without hypoglycaemia: results across four studies of saxagliptin. Int J Clin Pract. 2013 Aug;67(8):759-67. doi: 10.1111/ijcp.12212. Epub 2013 Jun 24.
• 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. doi: 10.3810/pgm.2011.07.2305.
• 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. doi: 10.1210/jc.2009-0550. Epub 2009 Oct 28.
• 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. doi: 10.1177/1479164111404575.

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: February 22, 2006
• First Submitted That Met QC Criteria: February 22, 2006
• First Posted (Estimate): February 24, 2006

Study Record Updates

• Last Update Posted (Estimate): April 7, 2015
• Last Update Submitted That Met QC Criteria: March 18, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Pioglitazone; Rosiglitazone; Saxagliptin
• Other Study ID Numbers: CV181-013