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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Metformin; Drug: Dapagliflozin; Drug: Dapagliflozin placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 1067
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2R 0X7
      • Local Institution
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 2H4
      • Local Institution
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
      • Local Institution
  • New Brunswick
    • Bathurst, New Brunswick, Canada, E2A 4X7
      • Local Institution
    • Moncton, New Brunswick, Canada, E1G 1A7
      • Local Institution
  • Newfoundland and Labrador
    • Mount Pearl, Newfoundland and Labrador, Canada, A1N 1W7
      • Local Institution
    • St-John, Newfoundland and Labrador, Canada, A1E 2E2
      • Local Institution
    • St. John'S, Newfoundland and Labrador, Canada, A1A 3R5
      • Local Institution
  • Ontario
    • Oakville, Ontario, Canada, L6H 3P1
      • Local Institution
    • Sarnia, Ontario, Canada, N7T 4X3
      • Local Institution
    • Thornhill, Ontario, Canada, L4J 8L7
      • Local Institution
    • Toronto, Ontario, Canada, M4R 2G4
      • Local Institution
    • Toronto, Ontario, Canada, M9W 4L6
      • Local Institution
  • Prince Edward Island
    • Charlottetown, Prince Edward Island, Canada, C1A 5Y9
      • Local Institution
  • Quebec
    • Drummondville, Quebec, Canada, J2B 7T1
      • Local Institution
    • Granby, Quebec, Canada, J2G 8Z9
      • Local Institution
    • L'Ancienne Lorette, Quebec, Canada, G2E 2X1
      • Local Institution
    • Mirabel, Quebec, Canada, J7J 2K8
      • Local Institution
    • St-Leonard, Quebec, Canada, H1S 3A9
      • Local Institution
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 3H3
      • Local Institution
    • Saskatoon, Saskatchewan, Canada, S7K 7H9
      • Local Institution
• Mexico
  • Aguascalientes, Mexico, 20230
    • Local Institution
  • Durango, Mexico, 34000
    • Local Institution
  • Baja California
    • Tijuana, Baja California, Mexico, 22320
      • Local Institution
  • Distrito Federal
    • Guadalajara, Distrito Federal, Mexico, 44670
      • Local Institution
    • Mexico, D. F., Distrito Federal, Mexico, 06726
      • Local Institution
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44100
      • Local Institution
    • Guadalajara, Jalisco, Mexico, 44600
      • Local Institution
    • Guadalajara, Jalisco, Mexico, 44680
      • Local Institution
  • Michioacan
    • Morelia, Michioacan, Mexico, 58070
      • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64060
      • Local Institution
    • Monterrrey, Nuevo Leon, Mexico, 64700
      • Local Institution
  • Yucatan
    • Merida, Yucatan, Mexico, 97070
      • Local Institution
• Russian Federation
  • Kursk, Russian Federation, 305035
    • Local Institution
  • Moscow, Russian Federation, 115093
    • Local Institution
  • Saint-Petersburg, Russian Federation, 191015
    • Local Institution
  • Smolensk, Russian Federation, 214019
    • Local Institution
  • St. Petersburg, Russian Federation, 195257
    • Local Institution
  • St.Petersburg, Russian Federation, 195112
    • Local Institution
  • Yaroslaval, Russian Federation, 150003
    • Local Institution
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85051
      • 43rd Medical Associates, P.C.
    • Tempe, Arizona, United States, 85282
      • Clinical Research Advantage, Inc
    • Tempe, Arizona, United States, 85282
      • Clin Res Advantage, Inc/East Valley Family Physicians, Plc
  • California
    • Fresno, California, United States, 93720
      • Valley Research
    • Los Gatos, California, United States, 95032
      • Cherlin, Richard
    • San Diego, California, United States, 92117
      • Ritchken & First M.D.'S
    • Torrance, California, United States, 90717
      • Torrance Clinical Research
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Aurora Family Medicine Center, P.C.
    • Colorado Springs, Colorado, United States, 80909
      • Expresscare Clinical Research
    • Denver, Colorado, United States, 80209
      • Denver Internal Medicine Group
    • Denver, Colorado, United States, 80209
      • Center For Internal Medicine
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Central Florida Clinical Trials
    • Chipley, Florida, United States, 32428
      • Family Care Associates
    • Jacksonville, Florida, United States, 32205
      • Westside Center for Clinical Research
    • Marianna, Florida, United States, 32446
      • Panhandle Family Care Associates
  • Louisiana
    • Slidell, Louisiana, United States, 70458
      • Louisiana Heart Center
  • Mississippi
    • Rolling Fork, Mississippi, United States, 39159
      • Jackson, Danny W.
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Woodlake Research
  • Nevada
    • Las Vegas, Nevada, United States, 89101
      • Nevada Alliance Against Diabetes
  • New York
    • New Hartford, New York, United States, 13413
      • Slocum-Dickson Medical Group, Pllc
    • Syracuse, New York, United States, 13210
      • Internist Associates Of Central New York, P. C.
    • West Seneca, New York, United States, 14224
      • Southgate Medical Group
  • Ohio
    • Dayton, Ohio, United States, 45439
      • Providence Health Partners
    • Newark, Ohio, United States, 43055
      • Newark Physician Associates
    • Zanesville, Ohio, United States, 43701
      • Physician Research, Inc.
  • Oklahoma
    • Bethany, Oklahoma, United States, 73008
      • Gilbert Medical Research, Llc
    • Yukon, Oklahoma, United States, 73109
      • Integris Family Care Yukon
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15216
      • Banksville Medical, Pc
  • South Carolina
    • Taylors, South Carolina, United States, 29687
      • Southeastern Research Associates, Inc.
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
  • Texas
    • Houston, Texas, United States, 77024
      • Village Family Practice
    • San Antonio, Texas, United States, 78229
      • Sam Clinical Research Center
    • San Antonio, Texas, United States, 78224
      • Abbott Clinical Research Group, Inc.
  • Utah
    • Bountiful, Utah, United States, 84010
      • Taylor/Wade Medical
    • Salt Lake City, Utah, United States, 84102
      • Optimum Clinical Research, Inc.
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Tidewater Integrated Medical Research
  • Washington
    • Spokane, Washington, United States, 99216
      • William L. Gray, Md

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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

Key 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Metformin; Other Names: Tablets, 500-2000 mg, orally as needed in any arm for rescue, based on protocol specific criteria; Drug: Dapagliflozin; Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks; Other Names: BMS-512148
Experimental: 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.	Drug: Metformin; Other Names: Tablets, 500-2000 mg, orally as needed in any arm for rescue, based on protocol specific criteria; Drug: Dapagliflozin; Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks; Other Names: BMS-512148
Experimental: 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.	Drug: Metformin; Other Names: Tablets, 500-2000 mg, orally as needed in any arm for rescue, based on protocol specific criteria; Drug: Dapagliflozin; Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks; Other Names: BMS-512148
Experimental: 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.	Drug: Metformin; Other Names: Tablets, 500-2000 mg, orally as needed in any arm for rescue, based on protocol specific criteria; Drug: Dapagliflozin; Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks; Other Names: BMS-512148
Experimental: 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.	Drug: Metformin; Other Names: Tablets, 500-2000 mg, orally as needed in any arm for rescue, based on protocol specific criteria; Drug: Dapagliflozin; Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks; Other Names: BMS-512148
Experimental: 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.	Drug: Metformin; Other Names: Tablets, 500-2000 mg, orally as needed in any arm for rescue, based on protocol specific criteria; Drug: Dapagliflozin; Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks; Other Names: BMS-512148
Experimental: 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.	Drug: Metformin; Other Names: Tablets, 500-2000 mg, orally as needed in any arm for rescue, based on protocol specific criteria; Drug: Dapagliflozin; Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks; Other Names: BMS-512148
Experimental: 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.	Drug: Metformin; Other Names: Tablets, 500-2000 mg, orally as needed in any arm for rescue, based on protocol specific criteria; Drug: Dapagliflozin placebo; Tablets, oral, 0 mg, once daily in the morning or evening for up to 102 weeks
Experimental: 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.	Drug: Metformin; Other Names: Tablets, 500-2000 mg, orally as needed in any arm for rescue, based on protocol specific criteria; Drug: Dapagliflozin; Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks; Other Names: BMS-512148

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 1	Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized in secondary efficacy analyses. Data after rescue medication were 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, glucose levels were recorded from the last postbaseline measurement prior to Week 24. For rescued participants, measurements obtained after initiation of rescue medication was not considered in calculating the endpoint.	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	Group 2 was an exploratory group, included to obtain initial efficacy and safety data. No comparator arm was included. Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Data after rescue medication were 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, glucose levels were recorded from the last postbaseline measurement prior to Week 24. For rescued participants, measurements obtained after initiation of rescue medication was not considered in calculating the endpoint.	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	Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. 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.	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	Secondary endpoints were tested using a 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.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.	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	Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured 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.	Baseline to Week 1 (end of Short-term Period)
Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 2	Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured 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.	Baseline to Week 1
Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1c] <7.0%) at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. 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. Thus, only key safety and efficacy analyses were performed for Group 2.	Baseline to Week 24 (end of Short-term Period)
Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) in Patients With Baseline HbA1c ≥9.0% (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. HbA1c was measured as % of hemoglobin by a central laboratory. The population included randomized patients who received treatment and had baseline HbA1c >9.0%. Data after rescue medication were excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of double-blind study drug. In cases where time of the first dose or 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 drug. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered exploratory, included to obtain initial data. No comparator arm was included. Thus, only key safety and efficacy analyses were performed in Group 2.	Baseline to Week 24 (end of Short-term Period)
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. 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. 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. Thus, only key safety and efficacy analyses were performed for Group 2.	Baseline to Week 24 (end of Short-term Period)
Adjusted Percentage of Participants Who Achieved Hemoglobin A1c [HbA1c] ≤6.5% (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. 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. Thus, only key safety and efficacy analyses were performed for Group 2.	Baseline to Week 24 (end of Short-term Period)
Adjusted Mean Change From Baseline to Week 24 in Total Body Weight in Patients With Baseline Body Mass Index ≥27 kg/m^2 (Last Observation Carried Forward)	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. 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. Thus, only key safety and efficacy analyses were performed for Group 2.	Baseline to Week 24 (end of Short-term Period)
Number of Participants With Adverse Events (AE), Hypoglycemia, Related AEs, Death as Outcome, Related Serious AEs (SAEs), SAEs and AEs Leading to Discontinuation, and Hypoglycemia Leading to Discontinuation (Short-term + Long-term Periods)	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or missing relationship to study drug. Includes non-SAEs and hypoglycemia with onset on or after the first date/time of double-blind treatment and on or prior to the last day of short-term plus long-term treatment plus 4 days. Includes SAEs with onset on or after the first date/time of double-blind treatment and on or prior to the last day of short-term plus long-term treatment plus 30 days.	Day 1 to Week 102 (end of Long-term Period) + 30 days
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Laboratory Abnormality (Short-term and Long-term Periods)	Baseline was defined as the last assessment prior to the start of the first dose of the double-blind study medication. Data included from baseline up to and including the last day of treatment plus 4 days. Data after rescue were also included. ULN=upper limit of normal; preRX=pretreatment. Phosphorus, inorganic (high) defined as >=5.6 mg/dL for ages 17-65 years or >=5.1 mg/dL for ages >=66.	Baseline to Week 102 (end of Long-term Period)
Number of Participants With Elevated Levels of Liver Enzymes on Laboratory Test Results (Short-term and Long-term Periods)	Data after rescue was included. AST=aspartate aminotransferase; ALT=alanine aminotransferase; ALP=alkaline phosphatase. 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. Thus, only key safety and efficacy analyses were performed for Group 2.	Day 1 to Week 102 (end of Long-term Period)
Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Findings (Last Observation Carried Forward {LOCF])	12-Lead ECGs were performed at entry into lead-in period Day -7 visit and Week 24/end of treatment visit (LOCF) on participants who were supine. ECGs were assessed by the investigator. Baseline was Day -7 for this parameter, and data after rescue were included.The Week 102 value is the last observation, regardless of rescue prior to Week 102 if no Week 102 measurement was available. 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. Thus, only key safety and efficacy analyses were performed for Group 2.	Baseline to Week 24 (end of Short-term Period)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Anna Maria Langkilde, AstraZeneca

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.
• 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.
• 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.

Helpful Links

• MB102013_Clinical_Study_Protocol

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: September 11, 2007
• First Submitted That Met QC Criteria: September 11, 2007
• First Posted (Estimate): September 12, 2007

Study Record Updates

• Last Update Posted (Estimate): October 20, 2015
• Last Update Submitted That Met QC Criteria: September 30, 2015
• Last Verified: September 1, 2015

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: MB102-013 LT