A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled With Diet and Exercise
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin as Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise
1 other identifier
interventional
1,067
4 countries
78
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 type-2-diabetes
Started Sep 2007
Longer than P75 for phase_3 type-2-diabetes
78 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2007
CompletedFirst Submitted
Initial submission to the registry
September 11, 2007
CompletedFirst Posted
Study publicly available on registry
September 12, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2010
CompletedResults Posted
Study results publicly available
May 14, 2014
CompletedOctober 20, 2015
September 1, 2015
1.4 years
September 11, 2007
February 6, 2014
September 30, 2015
Conditions
Outcome Measures
Primary Outcomes (2)
Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1C (HbA1c) (Last Observation Carried Forward [LOCF]): Group 1
HbA1c was measured 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. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Evening dosing groups were summarized as exploratory endpoints.
Baseline to Week 24 (end of Short-term Period)
Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) (Last Observation Carried Forward [LOCF]): Group 2
HbA1c was measured 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. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Group 2 (patients with enrollment baseline HbA1c \>10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included.
Baseline to Week 24 (end of Short-term Period)
Secondary Outcomes (15)
Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 1
Baseline to Week 24 (end of Short-term Period)
Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 2
Baseline to Week 24 (end of Short-term Period)
Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 1
From Baseline to Week 24 (end of Short-term Period)
Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 2
From Baseline to Week 24 (end of Short-term Period)
Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 1
Baseline to Week 1 (end of Short-term Period)
- +10 more secondary outcomes
Study Arms (9)
Group 1: Dapagliflozin, 2.5 mg AM
EXPERIMENTALParticipants with hemoglobin A1c (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks.
Group 1: Dapagliflozin, 10 mg AM
EXPERIMENTALParticipants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks.
Group 1: Dapagliflozin 2.5 mg PM
EXPERIMENTALParticipants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks.
Group 1: Dapagliflozin, 5 mg PM
EXPERIMENTALParticipants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks.
Group 1: Dapagliflozin, 10 mg PM
EXPERIMENTALParticipants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks.
Group 2: Dapagliflozin, 5 mg AM
EXPERIMENTALParticipants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks.
Group 2: Dapagliflozin, 10 mg AM
EXPERIMENTALParticipants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks.
Group 1: Dapagliflozin placebo AM & PM
EXPERIMENTALParticipants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks.
Group 1: Dapaglifozon, 5 mg AM
EXPERIMENTALParticipants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks.
Interventions
Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks
Tablets, oral, 0 mg, once daily in the morning or evening for up to 102 weeks
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Bristol-Myers Squibbcollaborator
Study Sites (78)
43rd Medical Associates, P.C.
Phoenix, Arizona, 85051, United States
Clin Res Advantage, Inc/East Valley Family Physicians, Plc
Tempe, Arizona, 85282, United States
Clinical Research Advantage, Inc
Tempe, Arizona, 85282, United States
Valley Research
Fresno, California, 93720, United States
Cherlin, Richard
Los Gatos, California, 95032, United States
Ritchken & First M.D.'S
San Diego, California, 92117, United States
Torrance Clinical Research
Torrance, California, 90717, United States
Aurora Family Medicine Center, P.C.
Aurora, Colorado, 80012, United States
Expresscare Clinical Research
Colorado Springs, Colorado, 80909, United States
Center For Internal Medicine
Denver, Colorado, 80209, United States
Denver Internal Medicine Group
Denver, Colorado, 80209, United States
Central Florida Clinical Trials
Altamonte Springs, Florida, 32701, United States
Family Care Associates
Chipley, Florida, 32428, United States
Westside Center For Clinical Research
Jacksonville, Florida, 32205, United States
Panhandle Family Care Associates
Marianna, Florida, 32446, United States
Louisiana Heart Center
Slidell, Louisiana, 70458, United States
Jackson, Danny W.
Rolling Fork, Mississippi, 39159, United States
Woodlake Research
Chesterfield, Missouri, 63017, United States
Nevada Alliance Against Diabetes
Las Vegas, Nevada, 89101, United States
Slocum-Dickson Medical Group, Pllc
New Hartford, New York, 13413, United States
Internist Associates Of Central New York, P. C.
Syracuse, New York, 13210, United States
Southgate Medical Group
West Seneca, New York, 14224, United States
Providence Health Partners
Dayton, Ohio, 45439, United States
Newark Physician Associates
Newark, Ohio, 43055, United States
Physician Research, Inc.
Zanesville, Ohio, 43701, United States
Gilbert Medical Research, Llc
Bethany, Oklahoma, 73008, United States
Integris Family Care Yukon
Yukon, Oklahoma, 73109, United States
Banksville Medical, Pc
Pittsburgh, Pennsylvania, 15216, United States
Southeastern Research Associates, Inc.
Taylors, South Carolina, 29687, United States
Holston Medical Group
Kingsport, Tennessee, 37660, United States
Village Family Practice
Houston, Texas, 77024, United States
Abbott Clinical Research Group, Inc.
San Antonio, Texas, 78224, United States
Sam Clinical Research Center
San Antonio, Texas, 78229, United States
Taylor/Wade Medical
Bountiful, Utah, 84010, United States
Optimum Clinical Research, Inc.
Salt Lake City, Utah, 84102, United States
J. Lewis Research, Inc
Salt Lake City, Utah, 84121, United States
Tidewater Integrated Medical Research
Virginia Beach, Virginia, 23454, United States
William L. Gray, Md
Spokane, Washington, 99216, United States
Local Institution
Calgary, Alberta, T2R 0X7, Canada
Local Institution
Kelowna, British Columbia, V1Y 2H4, Canada
Local Institution
Winnipeg, Manitoba, R3E 3P4, Canada
Local Institution
Bathurst, New Brunswick, E2A 4X7, Canada
Local Institution
Moncton, New Brunswick, E1G 1A7, Canada
Local Institution
Mount Pearl, Newfoundland and Labrador, A1N 1W7, Canada
Local Institution
St. John's, Newfoundland and Labrador, A1A 3R5, Canada
Local Institution
St. John's, Newfoundland and Labrador, A1E 2E2, Canada
Local Institution
Oakville, Ontario, L6H 3P1, Canada
Local Institution
Sarnia, Ontario, N7T 4X3, Canada
Local Institution
Thornhill, Ontario, L4J 8L7, Canada
Local Institution
Toronto, Ontario, M4R 2G4, Canada
Local Institution
Toronto, Ontario, M9W 4L6, Canada
Local Institution
Charlottetown, Prince Edward Island, C1A 5Y9, Canada
Local Institution
Drummondville, Quebec, J2B 7T1, Canada
Local Institution
Granby, Quebec, J2G 8Z9, Canada
Local Institution
L'Ancienne-Lorette, Quebec, G2E 2X1, Canada
Local Institution
Mirabel, Quebec, J7J 2K8, Canada
Local Institution
Saint-Léonard, Quebec, H1S 3A9, Canada
Local Institution
Saskatoon, Saskatchewan, S7K 3H3, Canada
Local Institution
Saskatoon, Saskatchewan, S7K 7H9, Canada
Local Institution
Aguascalientes, Aguascalientes, 20230, Mexico
Local Institution
Durango, Durango, 34000, Mexico
Local Institution
Tijuana, Estado de Baja California, 22320, Mexico
Local Institution
Guadalajara, Jalisco, 44100, Mexico
Local Institution
Guadalajara, Jalisco, 44600, Mexico
Local Institution
Guadalajara, Jalisco, 44680, Mexico
Local Institution
Guadalajara, Mexico City, 44670, Mexico
Local Institution
Mexico, D. F., Mexico City, 06726, Mexico
Local Institution
Morelia, Michioacan, 58070, Mexico
Local Institution
Monterrey, Nuevo León, 64060, Mexico
Local Institution
Monterrrey, Nuevo León, 64700, Mexico
Local Institution
Mérida, Yucatán, 97070, Mexico
Local Institution
Kursk, 305035, Russia
Local Institution
Moscow, 115093, Russia
Local Institution
Saint Petersburg, 191015, Russia
Local Institution
Saint Petersburg, 195112, Russia
Local Institution
Saint Petersburg, 195257, Russia
Local Institution
Smolensk, 214019, Russia
Local Institution
Yaroslaval, 150003, Russia
Related Publications (5)
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.
PMID: 20566676RESULTBailey 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.
PMID: 25381876RESULTNatale 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.
PMID: 38770818DERIVEDMellander 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.
PMID: 27461213DERIVEDKohan 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.
PMID: 26894924DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Group 2 (patients with enrollment baseline HbA1c \>10% and ≤2%) was an exploratory group, included to obtain initial efficacy and safety data. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.
Results Point of Contact
- Title
- Boaz Hirshberg
- Organization
- AstraZeneca Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Anna Maria Langkilde
AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 11, 2007
First Posted
September 12, 2007
Study Start
September 1, 2007
Primary Completion
February 1, 2009
Study Completion
July 1, 2010
Last Updated
October 20, 2015
Results First Posted
May 14, 2014
Record last verified: 2015-09