Clinical trial NCT00683878: Add-on to Thiazolidinedione (TZD) Failures
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Combination With Thiazolidinedione Therapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Thiazolidinedione Therapy Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Astra Zeneca, Bristol-Myers Squibb
First posted: 2008-05-26
Enrollment: 972
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
Secondary outcomes:
measure: Adjusted Mean Change From Baseline in 120-minute Post-challenge Plasma Glucose (PPG) (mg/dL) at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
measure: Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Change From Baseline in Waist Circumference (cm) at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
measure: 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])
timeFrame: From Baseline to Week 24
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, Llc
state: Alabama
city: Ozark
country: United States
facility: Iicr
state: Alabama
city: Phoenix
country: United States
facility: 43rd Medical Associates, P.C.
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Advantage Inc / Desert Clinical Res, Llc
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Advantage, Inc
state: Arizona
city: Little Rock
country: United States
facility: Little Rock Family Practice Clinic
state: Arkansas
city: Searcy
country: United States
facility: Searcy Medical Center
state: Arkansas
city: Costa Mesa
country: United States
facility: Clinical Innovations, Inc.
state: California
city: Greenbrae
country: United States
facility: Marin Endocrine Care And Research, Inc.
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research
state: California
city: Los Angeles
country: United States
facility: Randall Shue, D.O.
state: California
city: Northridge
country: United States
facility: Diabetes Medical Center Of California
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: Redlands
country: United States
facility: Avastra Clinical Trials
state: California
city: Roseville
country: United States
facility: Sierra Clinical Research
state: California
city: San Diego
country: United States
facility: Ritchken & First M.D.'S
state: California
city: Santa Ana
country: United States
facility: Advantage Clinical Research
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Tustin
country: United States
facility: Diabetes Research Center
state: California
city: Aurora
country: United States
facility: Aurora Family Medicine Center, P.C.
state: Colorado
city: Denver
country: United States
facility: Denver Internal Medicine
state: Colorado
city: Altamonte Springs
country: United States
facility: Central Florida Clinical Trials
state: Florida
city: Chipley
country: United States
facility: Health First Clinical Research Group, Inc.
state: Florida
city: Coral Gables
country: United States
facility: Clinical Therapeutics Corporation
state: Florida
city: Jacksonville
country: United States
facility: Westside Center For Clinical Research
state: Florida
city: Marianna
country: United States
facility: Panhandle Family Care Associates
state: Florida
city: Miami
country: United States
facility: Baptist Diabetes Associates, Pa
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Res Inc.
state: Florida
city: Stone Mountain
country: United States
facility: Stone Mountain Clinical Research
state: Georgia
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Valparaiso
country: United States
facility: Northwest Indiana Center For Clinical Research
state: Indiana
city: Wichita
country: United States
facility: Professional Research Network Of Kansas
state: Kansas
city: Grand Rapids
country: United States
facility: St. Mary'S Center For Diabetes And Endocrinology
state: Michigan
city: Jackson
country: United States
facility: Endocrine Research Associates
state: Mississippi
city: Olive Branch
country: United States
facility: Olive Branch Family Medical Center
state: Mississippi
city: Rolling Fork
country: United States
facility: Danny W. Jackson P.A.
state: Mississippi
city: Las Vegas
country: United States
facility: Association Of International Professionals
state: Nevada
city: Toms River
country: United States
facility: Physicians Research Center
state: New Jersey
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Charlotte
country: United States
facility: Metrolina Internal Medicine
state: North Carolina
city: Charlotte
country: United States
facility: The Center For Nutrition & Preventive Medicine, Pllc
state: North Carolina
city: Lenoir
country: United States
facility: Northstate Clinical Research
state: North Carolina
city: Wilmington
country: United States
facility: New Hanover Medical Research
state: North Carolina
city: Dayton
country: United States
facility: Providence Health Partners - Center For Clinical Research
state: Ohio
city: Zanesville
country: United States
facility: Physician Research, Inc.
state: Ohio
city: Levittown
country: United States
facility: Family Medical Associates
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Banksville Medical, Pc
state: Pennsylvania
city: Pottstown
country: United States
facility: Brookside Family Practice & Pediatrics
state: Pennsylvania
city: Columbia
country: United States
facility: Columbia Clinical Research, Inc.
state: South Carolina
city: Taylors
country: United States
facility: Southeastern Research Associates, Inc.
state: South Carolina
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Dallas
country: United States
facility: Dallas Diabetes & Endocrine Center
state: Texas
city: Houston
country: United States
facility: Village Family Practice
state: Texas
city: Houston
country: United States
facility: Office Of Dr. Michelle Zaniewski Singh
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Research Assoc,, Inc.
state: Texas
city: Virginia Beach
country: United States
facility: Tidewater Integrated Medical Research
state: Virginia
city: Spokane
country: United States
facility: William L. Gray, Md
state: Washington
city: Ciudad Auton
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Zarate
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Local Institution
city: Winnipeg
country: Canada
facility: Local Institution
state: Manitoba
city: Moncton
country: Canada
facility: Local Institution
state: New Brunswick
city: Mount Pearl
country: Canada
facility: Local Institution
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Local Institution
state: Nova Scotia
city: Sarnia
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Mirabel
country: Canada
facility: Local Institution
state: Quebec
city: Hariyana
country: India
facility: Local Institution
city: Mumbai
country: India
facility: Local Institution
city: Vellore
country: India
facility: Local Institution
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Zapopan
country: Mexico
facility: Local Institution
state: Jalisco
city: Monterrey, Nl
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Merida
country: Mexico
facility: Local Institution
state: Yucatan
city: Chihuahua
country: Mexico
facility: Local Institution
city: Veracruz
country: Mexico
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Cebu City
country: Philippines
facility: Local Institution
city: Manila
country: Philippines
facility: Local Institution
city: Pasig City
country: Philippines
facility: Local Institution
city: Ponce
country: Puerto Rico
facility: Local Institution
city: Changhua
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Shah M, Stolbov L, Yakovleva T, Tang W, Sokolov V, Penland RC, Boulton D, Parkinson J. A model-based approach to investigating the relationship between glucose-insulin dynamics and dapagliflozin treatment effect in patients with type 2 diabetes. Diabetes Obes Metab. 2021 Apr;23(4):991-1000. doi: 10.1111/dom.14305. Epub 2021 Jan 25.
citation: 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.
citation: Rosenstock J, Vico M, Wei L, Salsali A, List JF. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care. 2012 Jul;35(7):1473-8. doi: 10.2337/dc11-1693. Epub 2012 Mar 23.