Study of BMS-477118 as Monotherapy With Titration in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin as Monotherapy With Titration in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise

The purpose of this trial is to understand if saxagliptin is more effective than placebo as a treatment for type 2 diabetic subjects who are not controlled with diet and exercise

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Drug: Saxagliptin; Drug: Saxagliptin; Drug: Saxagliptin; Drug: Saxagliptin; 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 (rescue medication) added onto their blinded study medication

• Study Type: Interventional
• Enrollment (Actual): 365
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Bangalore, India, 560034
    • Local Institution
  • Mumbai, India, 400007
    • Local Institution
  • Mumbai, India, 400021
    • Local Institution
  • Nagpur, India, 440012
    • Local Institution
  • Karnataka
    • Manipal, Karnataka, India, 576104
      • Local Institution
  • Kerala
    • Kochi, Kerala, India, 682026
      • Local Institution
  • Mangalore
    • Attavar, Mangalore, India, 575001
      • Local Institution
  • New Delhi
    • Sarita Vihar, New Delhi, India, 110076
      • Local Institution
• Russian Federation
  • Moscov, Russian Federation, 118089
    • Local Institution
  • Moscow, Russian Federation, 115487
    • Local Institution
  • Nizhniy Novgorod, Russian Federation, 603126
    • Local Institution
  • Saint Petersburg, Russian Federation, 198013
    • Local Institution
  • Saratov, Russian Federation, 410018
    • Local Institution
  • Saratov, Russian Federation, 410054
    • Local Institution
  • Smolensk, Russian Federation, 214018
    • Local Institution
  • St.Petersburg, Russian Federation, 194156
    • Local Institution
  • Volgograd, Russian Federation, 400138
    • Local Institution
• Taiwan
  • Changhua, Taiwan, 500
    • Local Institution
  • Kaohsiung County, Taiwan, 833
    • Local Institution
  • Taichung, Taiwan, 402
    • Local Institution
  • Taichung City, Taiwan, 407
    • Local Institution
  • Taipei City, Taiwan, 114
    • Local Institution
  • Tao-Yuan County, Taiwan, 333
    • Local Institution
• United States
  • Alabama
    • Columbiana, Alabama, United States, 35051
      • Tomac, Inc.
    • Haleyville, Alabama, United States, 35565
      • Winston Technology, Inc.
  • Arizona
    • Mesa, Arizona, United States, 85213
      • Clinical Reseacrh Advantage/ Brown Family Medicine
  • California
    • Bakersfield, California, United States, 93311
      • Strategos Medical Group
    • Burbank, California, United States, 91505
      • Providence Clinical Research
    • Cudahy, California, United States, 90201
      • Rx for Life, Inc
    • Encino, California, United States, 91436
      • Medical Group of Encino
    • Fountain Valley, California, United States, 92708
      • Southland Clinical Research Center, Inc.
    • Fresno, California, United States, 93720
      • Valley Research
    • Northridge, California, United States, 91325
      • Diabetes Medical Center of California
    • Pico Rivera, California, United States, 90660
      • In Private Prictice Clinic
    • San Jose, California, United States, 95128
      • San Jose Clinical Research, Inc.
  • Florida
    • Altamonte Springs, Florida, United States, 32714
      • Central Florida Clinical Trials, Inc.
    • Melbourne, Florida, United States, 32935
      • Accelovance
    • Sarasota, Florida, United States, 34243
      • University Family Healthcare, Pa
    • St. Petersburg, Florida, United States, 33707
      • Premier Healthcare
  • Kansas
    • Overland Park, Kansas, United States, 66215
      • Pinnacle Medical Research
  • Missouri
    • Kansas City, Missouri, United States, 64106
      • Kansas City University Of Medicine And Biosciences
    • Wentzville, Missouri, United States, 63385
      • Primary Care Physicians, Pc
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Physicians Research Center
  • New York
    • Kingston, New York, United States, 12401
      • Hudson Valley Clinical Research Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28262
      • Neem Research Group of Charlotte
    • Greenville, North Carolina, United States, 27834
      • Diabetes Center- East Carolina University
    • Salisbury, North Carolina, United States, 28144
      • Crescent Medical Research
  • Ohio
    • Barberton, Ohio, United States, 44203
      • Community Health Care, Inc.
    • Canton, Ohio, United States, 44718
      • Clinical Research Limited
    • Kettering, Ohio, United States, 45429
      • Wells Institute for Health Awareness
    • Perrysburg, Ohio, United States, 43551
      • Clinical Research Source, Inc
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Accelovance
    • Oklahoma City, Oklahoma, United States, 73170
      • Integris Family Care South
  • Oregon
    • Eugene, Oregon, United States, 97404
      • The Office Of Patricia Buchanan
  • Pennsylvania
    • Carlisle, Pennsylvania, United States, 17015
      • Cumberland Valley Endocrinology Center, Llc
    • Fleetwood, Pennsylvania, United States, 19522
      • Fleetwood Clinical Research
    • Pittsburgh, Pennsylvania, United States, 15216
      • Banksville Medical, Pc
    • Shippensburg, Pennsylvania, United States, 17257
      • Biomedical Research Associates, Llc
  • South Carolina
    • Duncan, South Carolina, United States, 29334
      • Middle Tyger Family Medicine
    • Taylors, South Carolina, United States, 29687
      • Southeastern Research Assoc
  • Tennessee
    • Bartlett, Tennessee, United States, 38134
      • Versoza & Ungab Internal Medicine Associates
    • Collierville, Tennessee, United States, 38017
      • Collierville Medical Specialist
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
    • Memphis, Tennessee, United States, 38116
      • Med-South Research
    • Memphis, Tennessee, United States, 38125
      • Southwind Medical Specialist
  • Texas
    • Carrollton, Texas, United States, 75010
      • Precision Family Medicine
    • Corpus Christi, Texas, United States, 78411
      • Alpha Therapy Research Center
    • Houston, Texas, United States, 77081
      • Texas Center For Drug Development, P.A.
    • Houston, Texas, United States, 77024
      • Village Family Practice
    • San Antonio, Texas, United States, 78224
      • Abbott Clinical Research Group, Inc
  • Utah
    • Bountiful, Utah, United States, 84010
      • Taylor/Wade Medical
    • Salt Lake City, Utah, United States, 84102
      • Optimum Clinical Research
  • Virginia
    • Virginia Beach, Virginia, United States, 23451
      • Tidewater Integrated Medical Research
  • Washington
    • Spokane, Washington, United States, 99216
      • Spokane Internal Medicine

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 diabetes
• Inadequate blood sugar control

Exclusion Criteria:

• Previous treatment for diabetes
• Current treatment with other medications to lower blood sugar
• Major heart, liver or kidney problems
• Women who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saxagliptin 2.5 mg QAM (A); PLUS open-label metformin (as needed as rescue medication)	Drug: Saxagliptin; Coated tablets, Oral, 2.5 mg, QAM, Daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Coated tablets, Oral, 2.5 mg titrated to 5mg, QAM, Daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Coated tablets, Oral, 5mg, QAM, Daily, (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Coated tablets, Oral, 5mg QPM, Daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: metformin; Tablets, Oral, 500-2000 mg, as needed (12 months LT)
Experimental: Saxagliptin 2.5 mg titrated to 5 mg QAM (B); PLUS open-label metformin (as needed as rescue medication)	Drug: Saxagliptin; Coated tablets, Oral, 2.5 mg, QAM, Daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Coated tablets, Oral, 2.5 mg titrated to 5mg, QAM, Daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Coated tablets, Oral, 5mg, QAM, Daily, (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Coated tablets, Oral, 5mg QPM, Daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: metformin; Tablets, Oral, 500-2000 mg, as needed (12 months LT)
Experimental: Saxagliptin 5 mg QAM (C); PLUS open-label metformin (as needed as rescue medication)	Drug: Saxagliptin; Coated tablets, Oral, 2.5 mg, QAM, Daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Coated tablets, Oral, 2.5 mg titrated to 5mg, QAM, Daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Coated tablets, Oral, 5mg, QAM, Daily, (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Coated tablets, Oral, 5mg QPM, Daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: metformin; Tablets, Oral, 500-2000 mg, as needed (12 months LT)
Experimental: Saxagliptin 5 mg QPM (D); PLUS open-label metformin (as needed as rescue medication)	Drug: Saxagliptin; Coated tablets, Oral, 2.5 mg, QAM, Daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Coated tablets, Oral, 2.5 mg titrated to 5mg, QAM, Daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Coated tablets, Oral, 5mg, QAM, Daily, (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: Saxagliptin; Coated tablets, Oral, 5mg QPM, Daily (6 months ST, 12 months LT); Other Names: BMS-477118; Drug: metformin; Tablets, Oral, 500-2000 mg, as needed (12 months LT)
Placebo Comparator: Placebo (E); PLUS open-label metformin (as needed as rescue medication)	Drug: metformin; Tablets, Oral, 500-2000 mg, as needed (12 months LT); Drug: Placebo; Coated tablets, Oral, 0mg, 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 A1 (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 A1C at Week 24 - Saxagliptin 5 mg QPM	Mean change from baseline in A1C at Week 24, adjusted for baseline value.	Baseline, Week 24
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 Diabetes Association's defined goal for glycemia, at each dose of saxagliptin versus placebo 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 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.
• Frederich R, McNeill R, Berglind N, Fleming D, Chen R. The efficacy and safety of the dipeptidyl peptidase-4 inhibitor saxagliptin in treatment-naive patients with type 2 diabetes mellitus: a randomized controlled trial. Diabetol Metab Syndr. 2012 Jul 24;4(1):36. doi: 10.1186/1758-5996-4-36.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: April 18, 2006
• First Submitted That Met QC Criteria: April 19, 2006
• First Posted (Estimate): April 20, 2006

Study Record Updates

• Last Update Posted (Estimate): April 29, 2015
• Last Update Submitted That Met QC Criteria: April 8, 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; 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; Saxagliptin
• Other Study ID Numbers: CV181-038