A Trial of BMS-512148 in Patients With Type 2 Diabetes Mellitus

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 2 Trial to Evaluate the Safety and Efficacy of BMS-512148 as Monotherapy in Subjects With Type 2 Diabetes Mellitus Who Are Treatment Naive And Have Inadequate Glycemic Control on Diet and Exercise

The purpose of this clinical research study is to learn if BMS-512148 is effective in controlling blood sugar levels as determined by HbA1c and fasting plasma glucose in patients who have been diagnosed with Type 2 diabetes. Patients should first try to control their diabetes with diet and exercise and should not have previously been treated for their diabetes (very short periods of time are acceptable). The safety of BMS512148 will also be studied

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: dapagliflozin; Drug: dapagliflozin; Drug: dapagliflozin; Drug: dapagliflozin; Drug: dapagliflozin; Drug: placebo; Drug: metformin

• Study Type: Interventional
• Enrollment (Actual): 389
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Local Institution
    • Edmonton, Alberta, Canada
      • Local Institution
  • British Columbia
    • Langley, British Columbia, Canada
      • Local Institution
    • Surrey, British Columbia, Canada
      • Local Institution
    • Vancouver, British Columbia, Canada
      • Local Institution
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • Local Institution
  • New Brunswick
    • Bathurst, New Brunswick, Canada
      • Local Institution
    • Moncton, New Brunswick, Canada
      • Local Institution
    • St. John's, New Brunswick, Canada
      • Local Institution
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada
      • Local Institution
  • Ontario
    • Corunna, Ontario, Canada
      • Local Institution
    • Etobicoke, Ontario, Canada
      • Local Institution
    • Kitchener, Ontario, Canada
      • Local Institution
    • Newmarket, Ontario, Canada
      • Local Institution
    • Sarnia, Ontario, Canada
      • Local Institution
    • Toronto, Ontario, Canada
      • Local Institution
  • Prince Edward Island
    • Charlottetown, Prince Edward Island, Canada
      • Local Institution
  • Quebec
    • Drummondville, Quebec, Canada
      • Local Institution
    • Granby, Quebec, Canada
      • Local Institution
    • Greenfield Park, Quebec, Canada
      • Local Institution
    • Rimouski, Quebec, Canada
      • Local Institution
    • St-Leonard, Quebec, Canada
      • Local Institution
    • Ste-Foy, Quebec, Canada
      • Local Institution
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • Local Institution
• Mexico
  • Aguascalientes, Mexico
    • Local Institution
  • Durango, Mexico
    • Local Institution
  • Jalisco
    • Guadalajara, Jalisco, Mexico
      • Local Institution
    • Zapopan, Jalisco, Mexico
      • Local Institution
  • Morelos
    • Cuernavaca, Morelos, Mexico
      • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico
      • Local Institution
• Puerto Rico
  • Caguas, Puerto Rico
    • Local Institution
  • Manati, Puerto Rico
    • Local Institution
  • San Juan, Puerto Rico
    • Local Institution
• United States
  • Alabama
    • Bayou La Batre, Alabama, United States
      • Local Institution
    • Birmingham, Alabama, United States
      • Local Institution
    • Huntsville, Alabama, United States
      • Local Institution
    • Mobile, Alabama, United States
      • Local Institution
  • Arizona
    • Chandler, Arizona, United States
      • Local Institution
    • Tucson, Arizona, United States
      • Local Institution
  • Arkansas
    • Fayetteville, Arkansas, United States
      • Local Institution
    • Hot Springs, Arkansas, United States
      • Local Institution
  • California
    • Beverly Hills, California, United States
      • Local Institution
    • Long Beach, California, United States
      • Local Institution
    • Los Gatos, California, United States
      • Local Institution
    • Mission Viejo, California, United States
      • Local Institution
    • Orange, California, United States
      • Local Institution
    • Redondo Beach, California, United States
      • Local Institution
    • San Diego, California, United States
      • Local Institution
    • Torrance, California, United States
      • Local Institution
  • Colorado
    • Colorado Springs, Colorado, United States
      • Local Institution
    • Denver, Colorado, United States
      • Local Institution
  • Florida
    • Boynton Beach, Florida, United States
      • Local Institution
    • Brandon, Florida, United States
      • Local Institution
    • Delray Beach, Florida, United States
      • Local Institution
    • Holly Hill, Florida, United States
      • Local Institution
    • Jacksonville, Florida, United States
      • Local Institution
    • Jacksonville, Florida, United States
      • Local Instiuttion
    • New Port Richey, Florida, United States
      • Local Institution
    • Orlando, Florida, United States
      • Local Institution
    • Ormond Beach, Florida, United States
      • Local Institution
  • Georgia
    • Augusta, Georgia, United States
      • Local Institution
    • Blue Ridge, Georgia, United States
      • Local Institution
  • Hawaii
    • Honolulu, Hawaii, United States
      • Local Institution
  • Indiana
    • Indianapolis, Indiana, United States
      • Local Institution
    • Lafayette, Indiana, United States
      • Local Institution
  • Kansas
    • Arkansas City, Kansas, United States
      • Local Institution
  • Louisiana
    • Baton Rouge, Louisiana, United States
      • Local Institution
  • Maryland
    • Columbia, Maryland, United States
      • Local Institution
    • Elkton, Maryland, United States
      • Local Institution
  • Massachusetts
    • Sudbury, Massachusetts, United States
      • Local Institution
    • Worcester, Massachusetts, United States
      • Local Institution
  • Michigan
    • Dearborn, Michigan, United States
      • Local Institution
    • Royal Oak, Michigan, United States
      • Local Institution
  • Minnesota
    • Brooklyn Center, Minnesota, United States
      • Local Institution
    • Edina, Minnesota, United States
      • Local Insitution
    • Minneapolis, Minnesota, United States
      • Local Institution
  • Mississippi
    • Hattiesburg, Mississippi, United States
      • Local Institution
    • Jackson, Mississippi, United States
      • Local Institution
  • Missouri
    • Chesterfield, Missouri, United States
      • Local Institution
    • Kansas City, Missouri, United States
      • Local Institution
    • St. Louis, Missouri, United States
      • Local Institution
  • Nebraska
    • Scottsbluff, Nebraska, United States
      • Local Institution
  • Nevada
    • North Las Vegas, Nevada, United States
      • Local Institution
  • New Mexico
    • Albuquerque, New Mexico, United States
      • Local Institution
    • Alburquerque, New Mexico, United States
      • Local Institution
    • Los Alamos, New Mexico, United States
      • Local Institution
  • New York
    • Albany, New York, United States
      • Local Institution
    • Bronxville, New York, United States
      • Local Institution
    • Camillus, New York, United States
      • Local Institution
    • Cooperstown, New York, United States
      • Local Institution
    • New Hyde Park, New York, United States
      • Local Instiution
    • West Seneca, New York, United States
      • Local Institution
  • North Carolina
    • Charlotte, North Carolina, United States
      • Local Institution
    • High Point, North Carolina, United States
      • Local Institution
    • Morehead City, North Carolina, United States
      • Local Institution
    • Raleigh, North Carolina, United States
      • Local Institution
    • Wilmington, North Carolina, United States
      • Local Institution
  • Ohio
    • Akron, Ohio, United States
      • Local Institution
    • Beachwood, Ohio, United States
      • Local Institution
    • Cincinnati, Ohio, United States
      • Local Institution
    • Cleveland, Ohio, United States
      • Local Institution
    • Dayton, Ohio, United States
      • Local Institution
    • Mogadore, Ohio, United States
      • Local Institution
    • Newark, Ohio, United States
      • Local Institution
    • Zanesville, Ohio, United States
      • Local Institution
  • Oklahoma
    • Bethany, Oklahoma, United States
      • Local Institution
    • Yukon, Oklahoma, United States
      • Local Institution
  • Oregon
    • Bend, Oregon, United States
      • Local Institution
    • Eugene, Oregon, United States
      • Local Institution
    • Hillsboro, Oregon, United States
      • Local Institution
    • Portland, Oregon, United States
      • Local Institution
  • Pennsylvania
    • Bensalem, Pennsylvania, United States
      • Local Institution
    • Feasterville, Pennsylvania, United States
      • Local Institution
    • Levittown, Pennsylvania, United States
      • Local Institution
    • Morrisville, Pennsylvania, United States
      • Local Institution
    • Reading, Pennsylvania, United States
      • Local Institution
  • Rhode Island
    • Cumberland, Rhode Island, United States
      • Local Institution
    • Johnston, Rhode Island, United States
      • Local Institution
  • South Carolina
    • Anderson, South Carolina, United States
      • Local Institution
    • Simpsonville, South Carolina, United States
      • Local Institution
    • Summerville, South Carolina, United States
      • Local Institution
    • Taylors, South Carolina, United States
      • Local Institution
  • South Dakota
    • Rapid City, South Dakota, United States
      • Local Institution
  • Tennessee
    • Memphis, Tennessee, United States
      • Local Institution
    • Nashville, Tennessee, United States
      • Local Institution
    • Selmer, Tennessee, United States
      • Local Institution
  • Texas
    • Austin, Texas, United States
      • Local Institution
    • Bellaire, Texas, United States
      • Local Institution
    • Bryan, Texas, United States
      • Local Institution
    • El Paso, Texas, United States
      • Local Institution
    • Houston, Texas, United States
      • Local Institution
    • Irving, Texas, United States
      • Local Institution
    • San Antonio, Texas, United States
      • Local Institution
  • Utah
    • Salt Lake City, Utah, United States
      • Local Institution
  • Virginia
    • Burke, Virginia, United States
      • Local Institution
    • Hampton, Virginia, United States
      • Local Institution
    • Norfolk, Virginia, United States
      • Local Institution
    • Richmond, Virginia, United States
      • Local Institution
    • Virginia Beach, Virginia, United States
      • Local Institution
  • Washington
    • Edmonds, Washington, United States
      • Local Institution
    • Renton, Washington, United States
      • Local Institution
    • Spokane, Washington, United States
      • Local Institution
    • Vancouver, Washington, United States
      • Local Institution
  • Wisconsin
    • Milwaukee, Wisconsin, United States
      • Local Institution
    • West Allis, Wisconsin, United States
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with Type 2 diabetes mellitus with inadequate glycemic control on diet and exercise. HbA1c >= 7% and <=10%.
• Patient either has not been previously treated with antihyperglycemic medication or has been treated for <30 days since diagnosis and has received less than 3 consecutive doses or 7 non-consecutive doses in the last 30 days.
• C-peptide > 1.0 ng/ml
• Body Mass Index <= 40 kg/m2
• Serum creatinine < 1.5 mg/dL for men or < 1.4 mg/dL for women.
• No overt proteinuria (microalbumin/creatinine ratio must be <300 mg/g

Exclusion Criteria:

• Unstable renal disease
• Patients with significant liver disease including chronic active hepatitis
• Within the last 6 months has had any of the following cardiovascular event: myocardial infarction, unstable angina, unstable CHF,NYHA Class III or IV CHF, TIA, unstable arrhythmia or cardiac revascularization surgery.
• Subjects with clinically significant anemia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: dapagliflozin; Tablets, Oral, 2.5 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 5 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 10 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 20 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 50 mg, Once daily, 12 weeks.
Experimental: Arm 2	Drug: dapagliflozin; Tablets, Oral, 2.5 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 5 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 10 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 20 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 50 mg, Once daily, 12 weeks.
Experimental: Arm 3	Drug: dapagliflozin; Tablets, Oral, 2.5 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 5 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 10 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 20 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 50 mg, Once daily, 12 weeks.
Experimental: Arm 4	Drug: dapagliflozin; Tablets, Oral, 2.5 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 5 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 10 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 20 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 50 mg, Once daily, 12 weeks.
Experimental: Arm 5	Drug: dapagliflozin; Tablets, Oral, 2.5 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 5 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 10 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 20 mg, Once daily, 12 weeks.; Drug: dapagliflozin; Tablets, Oral, 50 mg, Once daily, 12 weeks.
Placebo Comparator: Arm 6	Drug: placebo; Tablets, Oral, 0 mg, Once daily, 12 weeks.
Active Comparator: Arm 7	Drug: metformin; Tablets, Oral, >/= 1500 mg, Once daily, 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean change from baseline in HbA1c compared to placebo.	at 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean change from baseline in fasting plasma glucose, evaluate proportion of subjects who achieve a therapeutic response (HbA1c <7%); change from baseline in urinary glucose excretion	at Weeks 6 and 12

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Mellander A, Billger M, Johnsson E, Traff AK, Yoshida S, Johnsson K. Hypersensitivity Events, Including Potentially Hypersensitivity-Related Skin Events, with Dapagliflozin in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis. Clin Drug Investig. 2016 Nov;36(11):925-933. doi: 10.1007/s40261-016-0438-3.
• Kohan DE, Fioretto P, Johnsson K, Parikh S, Ptaszynska A, Ying L. The effect of dapagliflozin on renal function in patients with type 2 diabetes. J Nephrol. 2016 Jun;29(3):391-400. doi: 10.1007/s40620-016-0261-1. Epub 2016 Feb 19.
• List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care. 2009 Apr;32(4):650-7. doi: 10.2337/dc08-1863. Epub 2008 Dec 29.

Helpful Links

• MB102-008 _CSR_synopsis

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: December 7, 2005
• First Submitted That Met QC Criteria: December 7, 2005
• First Posted (Estimate): December 8, 2005

Study Record Updates

• Last Update Posted (Estimate): November 17, 2016
• Last Update Submitted That Met QC Criteria: November 16, 2016
• Last Verified: November 1, 2016

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; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Metformin
• Other Study ID Numbers: MB102-008