A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled With Diet and Exercise

NCT ID: NCT00528372

Last Updated: 2015-10-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1067 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2010-07-31

Brief Summary

The purpose of this clinical research study is to determine whether dapagliflozin can improve (decrease) blood glucose values in patients with Type 2 diabetes who have never been treated with medication or have been taking medication for less than 24 weeks since their original diabetes diagnosis. The safety of this treatment will also be studied.

Detailed Description

All eligible participants will receive single-blind placebo medication during the 2-week lead-in period. All participants may receive additional open-label treatment with metformin, 500-2000 mg, as needed for rescue, based on protocol specific criteria.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group 1: Dapagliflozin, 2.5 mg AM

Participants with hemoglobin A1c (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks.

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks

Metformin

Intervention Type: DRUG

Group 1: Dapagliflozin, 10 mg AM

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks.

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks

Metformin

Intervention Type: DRUG

Group 1: Dapagliflozin 2.5 mg PM

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks.

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks

Metformin

Intervention Type: DRUG

Group 1: Dapagliflozin, 5 mg PM

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks.

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks

Metformin

Intervention Type: DRUG

Group 1: Dapagliflozin, 10 mg PM

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks.

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks

Metformin

Intervention Type: DRUG

Group 2: Dapagliflozin, 5 mg AM

Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks.

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks

Metformin

Intervention Type: DRUG

Group 2: Dapagliflozin, 10 mg AM

Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks.

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks

Metformin

Intervention Type: DRUG

Group 1: Dapagliflozin placebo AM & PM

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks.

Group Type: EXPERIMENTAL

Dapagliflozin placebo

Intervention Type: DRUG

Tablets, oral, 0 mg, once daily in the morning or evening for up to 102 weeks

Metformin

Intervention Type: DRUG

Group 1: Dapaglifozon, 5 mg AM

Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks.

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks

Metformin

Intervention Type: DRUG

Interventions

Dapagliflozin

Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks

Intervention Type: DRUG

Dapagliflozin placebo

Tablets, oral, 0 mg, once daily in the morning or evening for up to 102 weeks

Intervention Type: DRUG

Metformin

Intervention Type: DRUG

Other Intervention Names

BMS-512148; Tablets, 500-2000 mg, orally as needed in any arm for rescue, based on protocol specific criteria

Eligibility Criteria

Inclusion Criteria

• Males and females, aged 18 to 77 years
• Type 2 diabetes with inadequate glycemic control, defined as: Group 1, hemoglobin A1c (HbA1c) ≥7% and ≤10%; Group 2, HbA1c ≥10.1% and ≤12.0%
• Drug naive, defined as never having received prescription medications for diabetes, having received prescription medications for diabetes for <24 weeks since the original diagnosis
• C-peptide ≥1.0 ng/mL at enrollment
• Body Mass Index ≤ 45.0 kg/m^2 at enrollment

Exclusion Criteria

• Urine albumin:creatinine ratio >1,800 mg/g
• Aspartate aminotransferase >3*upper limit of normal (ULN)
• Alanine aminotransferase >3*ULN
• Serum total bilirubin >2*ULN
• Serum creatinine ≥1.5 mg/dL for men; ≥1.4 mg/dLfor women
• Calcium value outside of the central laboratory normal reference range
• Positive hepatitis B surface antigen
• Positive anti-hepatitis C virus antibody
• Hemoglobin ≤11 g/dL for men; hemoglobin ≤10 g/dL for women
• Creatine kinase >3*ULN
• Abnormal free T4 values
• History of diabetes insipidus
• Symptoms of poorly controlled diabetes, including marked polyuria and polydipsia with greater than 10% weight loss in the 3 months prior to enrollment
• History of diabetic ketoacidosis or hyperosmolar nonketotic coma
• Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg
• Any of the following within 6 months of enrollment: Myocardial infarction, cardiac surgery or revascularization, unstable angina, unstable congestive heart failure (CHF), CHF New York Heart Association Class III or IV status, transient ischemic attack or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia
• History of unstable or rapidly progressing renal disease
• Conditions of congenital renal glucosuria
• Significant hepatic disease, including chronic active hepatitis and/or severe hepatic insufficiency
• Documented history of hepatotoxicity with any medication
• Documented history of severe hepatobiliary disease
• History of hemoglobinopathy, with the exception of sickle cell trait, thalassemia minor, or chronic or recurrent hemolysis
• Donation of blood or blood products to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of >400 mL of blood during the 6 weeks prior to enrollment
• Malignancy (with the exception of treated basal cell or treated squamous cell carcinoma) within 5 years of enrollment visit
• Known immunocompromised status, including individuals who had undergone organ transplantation or who had positive HIV results
• Administration of any antidiabetic therapy for more than 14 days (consecutive or not) during the 12 weeks prior to enrollment
• Administration of any antidiabetic therapy, other than any previously specified, at any dose, at any time during the 4 weeks prior to enrollment
• Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for >4 weeks within 3 months prior to enrollment
• History of bariatric surgery or lap-band procedure
• Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, and/or phendimetrazine, within 30 days of enrollment

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 77 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anna Maria Langkilde

Role: STUDY_DIRECTOR

AstraZeneca

Locations

43rd Medical Associates, P.C.

Phoenix, Arizona, United States

Clin Res Advantage, Inc/East Valley Family Physicians, Plc

Tempe, Arizona, United States

Clinical Research Advantage, Inc

Tempe, Arizona, United States

Valley Research

Fresno, California, United States

Cherlin, Richard

Los Gatos, California, United States

Ritchken & First M.D.'S

San Diego, California, United States

Torrance Clinical Research

Torrance, California, United States

Aurora Family Medicine Center, P.C.

Aurora, Colorado, United States

Expresscare Clinical Research

Colorado Springs, Colorado, United States

Center For Internal Medicine

Denver, Colorado, United States

Denver Internal Medicine Group

Denver, Colorado, United States

Central Florida Clinical Trials

Altamonte Springs, Florida, United States

Family Care Associates

Chipley, Florida, United States

Westside Center For Clinical Research

Jacksonville, Florida, United States

Panhandle Family Care Associates

Marianna, Florida, United States

Louisiana Heart Center

Slidell, Louisiana, United States

Jackson, Danny W.

Rolling Fork, Mississippi, United States

Woodlake Research

Chesterfield, Missouri, United States

Nevada Alliance Against Diabetes

Las Vegas, Nevada, United States

Slocum-Dickson Medical Group, Pllc

New Hartford, New York, United States

Internist Associates Of Central New York, P. C.

Syracuse, New York, United States

Southgate Medical Group

West Seneca, New York, United States

Providence Health Partners

Dayton, Ohio, United States

Newark Physician Associates

Newark, Ohio, United States

Physician Research, Inc.

Zanesville, Ohio, United States

Gilbert Medical Research, Llc

Bethany, Oklahoma, United States

Integris Family Care Yukon

Yukon, Oklahoma, United States

Banksville Medical, Pc

Pittsburgh, Pennsylvania, United States

Southeastern Research Associates, Inc.

Taylors, South Carolina, United States

Holston Medical Group

Kingsport, Tennessee, United States

Village Family Practice

Houston, Texas, United States

Abbott Clinical Research Group, Inc.

San Antonio, Texas, United States

Sam Clinical Research Center

San Antonio, Texas, United States

Taylor/Wade Medical

Bountiful, Utah, United States

Optimum Clinical Research, Inc.

Salt Lake City, Utah, United States

J. Lewis Research, Inc

Salt Lake City, Utah, United States

Tidewater Integrated Medical Research

Virginia Beach, Virginia, United States

William L. Gray, Md

Spokane, Washington, United States

Local Institution

Calgary, Alberta, Canada

Local Institution

Kelowna, British Columbia, Canada

Local Institution

Winnipeg, Manitoba, Canada

Local Institution

Bathurst, New Brunswick, Canada

Local Institution

Moncton, New Brunswick, Canada

Local Institution

Mount Pearl, Newfoundland and Labrador, Canada

Local Institution

St. John's, Newfoundland and Labrador, Canada

Local Institution

St. John's, Newfoundland and Labrador, Canada

Local Institution

Oakville, Ontario, Canada

Local Institution

Sarnia, Ontario, Canada

Local Institution

Thornhill, Ontario, Canada

Local Institution

Toronto, Ontario, Canada

Local Institution

Toronto, Ontario, Canada

Local Institution

Charlottetown, Prince Edward Island, Canada

Local Institution

Drummondville, Quebec, Canada

Local Institution

Granby, Quebec, Canada

Local Institution

L'Ancienne-Lorette, Quebec, Canada

Local Institution

Mirabel, Quebec, Canada

Local Institution

Saint-Léonard, Quebec, Canada

Local Institution

Saskatoon, Saskatchewan, Canada

Local Institution

Saskatoon, Saskatchewan, Canada

Local Institution

Aguascalientes, Aguascalientes, Mexico

Local Institution

Durango, Durango, Mexico

Local Institution

Tijuana, Estado de Baja California, Mexico

Local Institution

Guadalajara, Jalisco, Mexico

Local Institution

Guadalajara, Jalisco, Mexico

Local Institution

Guadalajara, Jalisco, Mexico

Local Institution

Guadalajara, Mexico City, Mexico

Local Institution

Mexico, D. F., Mexico City, Mexico

Local Institution

Morelia, Michioacan, Mexico

Local Institution

Monterrey, Nuevo León, Mexico

Local Institution

Monterrrey, Nuevo León, Mexico

Local Institution

Mérida, Yucatán, Mexico

Local Institution

Kursk, , Russia

Local Institution

Moscow, , Russia

Local Institution

Saint Petersburg, , Russia

Local Institution

Saint Petersburg, , Russia

Local Institution

Saint Petersburg, , Russia

Local Institution

Smolensk, , Russia

Local Institution

Yaroslaval, , Russia

Countries

United States; Canada; Mexico; Russia

References

Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010 Oct;33(10):2217-24. doi: 10.2337/dc10-0612. Epub 2010 Jun 21.

Reference Type: RESULT

PMID: 20566676 (View on PubMed)

Bailey CJ, Morales Villegas EC, Woo V, Tang W, Ptaszynska A, List JF. Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes: a randomized double-blind placebo-controlled 102-week trial. Diabet Med. 2015 Apr;32(4):531-41. doi: 10.1111/dme.12624. Epub 2014 Nov 22.

Reference Type: RESULT

PMID: 25381876 (View on PubMed)

Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

Reference Type: DERIVED

PMID: 38770818 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27461213 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26894924 (View on PubMed)

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3672&filename=MB102013_Clinical_Study_Protocol_Redacted.pdf

MB102013\_Clinical\_Study\_Protocol

Other Identifiers

MB102-013 LT

Identifier Type: -

Identifier Source: org_study_id