MedPath

Add-on to Thiazolidinedione (TZD) Failures

Registration Number
NCT00683878
Lead Sponsor
AstraZeneca
Brief Summary

The purpose of this clinical research study is to learn if BMS-512148 (Dapagliflozin) can help reduce the blood sugar levels in subjects with Type 2 Diabetes who are not well controlled on TZD alone. The safety of this treatment will also be studied

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
972
Inclusion Criteria
  • Males and females, ≥ 18 years old, with type 2 diabetes and with inadequate glycemic control
  • All subjects must have central laboratory pre-randomization A1C ≥ 7.0 and ≤ 10.5%
  • C-peptide ≥ 1.0 ng/mL (0.34 nmol/L)
  • Body Mass Index ≤ 45.0 kg/m²
Exclusion Criteria
  • AST and /or ALT > 2.5 times the upper limit of normal
  • Serum total bilirubin > 2 mg/dL (34.2 µmol/L)
  • Creatinine kinase > 3.0 times the upper limit of normal
  • Symptoms of severely uncontrolled diabetes
  • Serum creatinine ≥ 2.0 mg/dL
  • Calculated Cr-Clearance < 50 ml/min (calculated by Cockroft-Gault formula)
  • Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 2Thiazolidinedione (Pioglitazone)-
Arm 1Thiazolidinedione (Pioglitazone)-
Arm 3Thiazolidinedione (Pioglitazone)-
Arm 3Placebo matching Dapagliflozin-
Arm 1Dapagliflozin-
Arm 2Dapagliflozin-
Primary Outcome Measures
NameTimeMethod
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF])From Baseline to Week 24

HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the double-blind period.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])From Baseline to Week 24

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c \<7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. Mean and standard error for percentage of participants were estimated by modified logistic regression model.

Adjusted Mean Change From Baseline in Total Body Weight (kg) Among Subjects With Baseline Body Mass Index (BMI) ≥ 27 kg/m^2 at Week 24 (Last Observation Carried Forward [LOCF])From Baseline to Week 24

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight among subjects with baseline body mass index (BMI) ≥ 27 kg/m\^2 at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 of the double-blind period.

Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF])From Baseline to Week 24

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 of the double-blind period.

Adjusted Mean Change From Baseline in Waist Circumference (cm) at Week 24 (Last Observation Carried Forward [LOCF])From Baseline to Week 24

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in waist circumference at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Waist circumference measurements were obtained during the qualification and lead-in periods and on Day 1 and Week 24 of the double-blind period.

Adjusted Mean Change From Baseline in 120-minute Post-challenge Plasma Glucose (PPG) (mg/dL) at Week 24 (Last Observation Carried Forward [LOCF])From Baseline to Week 24

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. In post oral glucose tolerance test (OGTT), glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. PPG measurements were obtained on Day 1 and week 24 in the double-blind period.

Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF])From Baseline to Week 24

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 in the double-blind period.

Trial Locations

Locations (58)

Diabetes Research Center

🇺🇸

Tustin, California, United States

Endocrine Research Associates

🇺🇸

Jackson, Mississippi, United States

Dallas Diabetes & Endocrine Center

🇺🇸

Dallas, Texas, United States

Little Rock Family Practice Clinic

🇺🇸

Little Rock, Arkansas, United States

Clinical Research Advantage, Inc

🇺🇸

Tempe, Arizona, United States

Advantage Clinical Research

🇺🇸

Santa Ana, California, United States

Searcy Medical Center

🇺🇸

Searcy, Arkansas, United States

St. Mary'S Center For Diabetes And Endocrinology

🇺🇸

Grand Rapids, Michigan, United States

The Center For Nutrition & Preventive Medicine, Pllc

🇺🇸

Charlotte, North Carolina, United States

Randall Shue, D.O.

🇺🇸

Los Angeles, California, United States

Iicr

🇺🇸

Ozark, Alabama, United States

Clinical Innovations, Inc.

🇺🇸

Costa Mesa, California, United States

Banksville Medical, Pc

🇺🇸

Pittsburgh, Pennsylvania, United States

Holston Medical Group

🇺🇸

Kingsport, Tennessee, United States

Pinnacle Research Group, Llc

🇺🇸

Anniston, Alabama, United States

Northstate Clinical Research

🇺🇸

Lenoir, North Carolina, United States

Clinical Research Advantage Inc / Desert Clinical Res, Llc

🇺🇸

Tempe, Arizona, United States

Sierra Clinical Research

🇺🇸

Roseville, California, United States

Torrance Clinical Research

🇺🇸

Lomita, California, United States

Clinical Therapeutics Corporation

🇺🇸

Coral Gables, Florida, United States

Olive Branch Family Medical Center

🇺🇸

Olive Branch, Mississippi, United States

Danny W. Jackson P.A.

🇺🇸

Rolling Fork, Mississippi, United States

Physician Research, Inc.

🇺🇸

Zanesville, Ohio, United States

Professional Research Network Of Kansas

🇺🇸

Wichita, Kansas, United States

Diabetes Medical Center Of California

🇺🇸

Northridge, California, United States

Marin Endocrine Care And Research, Inc.

🇺🇸

Greenbrae, California, United States

Suncoast Clinical Res Inc.

🇺🇸

New Port Richey, Florida, United States

Health First Clinical Research Group, Inc.

🇺🇸

Chipley, Florida, United States

Westside Center For Clinical Research

🇺🇸

Jacksonville, Florida, United States

Cedar Crosse Research Center

🇺🇸

Chicago, Illinois, United States

Stone Mountain Clinical Research

🇺🇸

Stone Mountain, Georgia, United States

Northwest Indiana Center For Clinical Research

🇺🇸

Valparaiso, Indiana, United States

Physicians Research Center

🇺🇸

Toms River, New Jersey, United States

New Hanover Medical Research

🇺🇸

Wilmington, North Carolina, United States

Providence Health Partners - Center For Clinical Research

🇺🇸

Dayton, Ohio, United States

Tidewater Integrated Medical Research

🇺🇸

Virginia Beach, Virginia, United States

Local Institution

🇨🇳

Taipei, Taiwan

43rd Medical Associates, P.C.

🇺🇸

Phoenix, Arizona, United States

Ritchken & First M.D.'S

🇺🇸

San Diego, California, United States

Aurora Family Medicine Center, P.C.

🇺🇸

Aurora, Colorado, United States

Denver Internal Medicine

🇺🇸

Denver, Colorado, United States

Baptist Diabetes Associates, Pa

🇺🇸

Miami, Florida, United States

Village Family Practice

🇺🇸

Houston, Texas, United States

Office Of Dr. Michelle Zaniewski Singh

🇺🇸

Houston, Texas, United States

Diabetes & Glandular Disease Research Assoc,, Inc.

🇺🇸

San Antonio, Texas, United States

Association Of International Professionals

🇺🇸

Las Vegas, Nevada, United States

Central Florida Clinical Trials

🇺🇸

Altamonte Springs, Florida, United States

Brookside Family Practice & Pediatrics

🇺🇸

Pottstown, Pennsylvania, United States

Finger Lakes Clinical Research

🇺🇸

Rochester, New York, United States

Panhandle Family Care Associates

🇺🇸

Marianna, Florida, United States

Metrolina Internal Medicine

🇺🇸

Charlotte, North Carolina, United States

Family Medical Associates

🇺🇸

Levittown, Pennsylvania, United States

William L. Gray, Md

🇺🇸

Spokane, Washington, United States

Columbia Clinical Research, Inc.

🇺🇸

Columbia, South Carolina, United States

Southeastern Research Associates, Inc.

🇺🇸

Taylors, South Carolina, United States

Desert Medical Advances

🇺🇸

Palm Desert, California, United States

Avastra Clinical Trials

🇺🇸

Redlands, California, United States

Encompass Clinical Research

🇺🇸

Spring Valley, California, United States

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