Study of Dapagliflozin in Combination With Metformin XR to Initiate the Treatment of Type 2 Diabetes

A Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin 10 mg in Combination With Metformin as Initial Therapy as Compared With Dapagliflozin 10 mg Monotherapy and Metformin Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control

The primary purpose of this study is to compare the change from baseline in hemoglobin A1C achieved with dapagliflozin 10 mg in combination with metformin XR as compared with metformin XR monotherapy and compared with Dapagliflozin monotherapy, after 24 weeks of oral administration of double-blind treatment. The safety of treatment with dapagliflozin will also be assessed in this study

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Metformin XR; Drug: Metformin XR; Drug: metformin HCl Modified Release matching Placebo; Drug: dapagliflozin matching Placebo

• Study Type: Interventional
• Enrollment (Actual): 1093
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Jaipur, India, 302001
    • Local Institution
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500034
      • Local Institution
  • Chennai
    • Aminjikarai, Chennai, India, 600029
      • Local Institution
  • Karnal
    • Haryana, Karnal, India, 132001
      • Local Institution
  • Karnataka
    • Bangalore, Karnataka, India, 560054
      • Local Institution
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India, 452010
      • Local Institution
  • Maharashtra
    • Nagpur, Maharashtra, India, 440010
      • Local Institution
    • Nagpur, Maharashtra, India, 440012
      • Local Institution
  • Tamilnadu
    • Chennai, Tamilnadu, India, 600020
      • Local Institution
  • Uttar Pradesh
    • Ghaziabad, Uttar Pradesh, India, 201002
      • Local Institution
• Korea, Republic of
  • Daegu, Korea, Republic of, 700-721
    • Local Institution
  • Incheon, Korea, Republic of, 405-760
    • Local Institution
  • Seoul, Korea, Republic of, 137040
    • Local Institution
  • Gyeonggi-Do
    • Bucheon, Gyeonggi-Do, Korea, Republic of, 420-717
      • Local Institution
    • Goyang-Si, Gyeonggi-Do, Korea, Republic of, 410773
      • Local Institution
    • Guri-Si, Gyeonggi-Do, Korea, Republic of, 471-701
      • Local Institution
    • Sungnam, Gyeonggi-Do, Korea, Republic of, 463-070
      • Local Institution
• Mexico
  • Aguascalientes, Mexico, 20230
    • Local Institution
  • Durango, Mexico, 34000
    • Local Institution
  • Veracruz, Mexico, CP 91910
    • Local Institution
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44100
      • Local Institution
    • Guadalajara, Jalisco, Mexico, CP 44650
      • Local Institution
    • Guadalajara, Jalisco, Mexico, CP 44670
      • Local Institution
  • Michioacan
    • Morelia, Michioacan, Mexico, 58070
      • Local Institution
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62448
      • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Local Institution
    • Monterrey, Nuevo Leon, Mexico, 64000
      • Local Institution
  • Yucatan
    • Merida, Yucatan, Mexico, 97070
      • Local Institution
• Puerto Rico
  • Fajardo, Puerto Rico, 00738
    • Local Institution
  • Ponce, Puerto Rico, 00716
    • Local Institution
  • Ponce, Puerto Rico, 00717
    • Local Institution
  • San Juan, Puerto Rico, 00909
    • Local Institution
  • San Juan, Puerto Rico, 00920
    • Local Institution
  • San Juan, Puerto Rico, 00926
    • Local Institution
• Russian Federation
  • Ekaterinaburg, Russian Federation, 620043
    • Local Institution
  • Kemerovo, Russian Federation, 650029
    • Local Institution
  • Krasnoyarsk, Russian Federation, 660022
    • Local Institution
  • Moscov, Russian Federation, 119048
    • Local Institution
  • Moscow, Russian Federation, 105229
    • Local Institution
  • Moscow, Russian Federation, 125299
    • Local Institution
  • Moscow, Russian Federation, 140091
    • Local Institution
  • Nizhniy Novgorod, Russian Federation, 603126
    • Local Institution
  • Nizhniy Novgorod, Russian Federation, 603018
    • Local Institution
  • Novosibirsk, Russian Federation, 630091
    • Local Institution
  • Novosibirsk, Russian Federation, 630117
    • Local Institution
  • Saint Petersburg, Russian Federation, 194044
    • Local Institution
  • Saint-Petersburg, Russian Federation, 190068
    • Local Institution
  • Samara, Russian Federation, 443067
    • Local Institution
  • Saratov, Russian Federation, 410028
    • Local Institution
  • Smolensk, Russian Federation, 214018
    • Local Institution
  • St. Petersburg, Russian Federation, 191015
    • Local Institution
  • St. Petersburg, Russian Federation, 193312
    • Local Institution
  • St.Petersburg, Russian Federation, 191186
    • Local Institution
  • Tyumen, Russian Federation, 625023
    • Local Institution
  • Vladimir, Russian Federation, 600023
    • Local Institution
  • Volgograd, Russian Federation, 400001
    • Local Institution
  • Voronezh, Russian Federation, 394018
    • Local Institution
  • Yaroslavl, Russian Federation, 150003
    • Local Institution
  • Yaroslavl, Russian Federation, 150023
    • Local Institution
• United States
  • Alabama
    • Ozark, Alabama, United States, 36360
      • International Institute Of Clinical Research
  • Arizona
    • Tempe, Arizona, United States, 85282
      • Clinical Research Advantage, Inc.
    • Tempe, Arizona, United States, 85282
      • Clinical Research Advantage, Inc./Mesa Family Med Ctr, Pc
  • California
    • Concord, California, United States, 94520
      • John Muir Physician Network Clinical Research Center
    • Encinitas, California, United States, 92024
      • Encompass Clinical Research-North Coast
    • Fountain Valley, California, United States, 92708
      • Southland Clinical Research Center, Inc.
    • Fresno, California, United States, 93720
      • Valley Research
    • Huntington Park, California, United States, 90255
      • Del Rosario Medical Clinic, Inc.
    • Irvine, California, United States, 92618
      • Irvine Center for Clinical Research, Inc.
    • Redlands, California, United States, 92373
      • Pacific Sleep Medicine Services (Avastra Clinical Trials)
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Lynn Institute Of The Rockies
    • Denver, Colorado, United States, 80239
      • Radiant Research, Inc.
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Therapeutics Corporation
    • Miami, Florida, United States, 33145
      • NextPhase Clinical Trials, Inc.
    • Miami, Florida, United States, 33156
      • Baptist Diabetes Associates
    • W Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute, Inc.
  • Georgia
    • Hartwell, Georgia, United States, 30643
      • Lake Hartwell Family Medicine
    • Perry, Georgia, United States, 31069
      • Middle Georgia Drug Study Center, Llc
  • Idaho
    • Boise, Idaho, United States, 83704
      • Northwest Clinical Trials
  • Illinois
    • Addison, Illinois, United States, 60101
      • Provident Clinical Research
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center
    • Vernon Hills, Illinois, United States, 60061
      • Deerbrook Medical Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Physicians Research Group
  • Michigan
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Research Institute
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
      • Olive Branch Family Medical Center
  • New York
    • New York, New York, United States, 10019
      • Clinilabs, Inc.
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • Metrolina Medical Research
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Salisbury, North Carolina, United States, 28144
      • Crescent Medical Research
  • Ohio
    • Canal Fulton, Ohio, United States, 44614
      • Community Health Care, Inc.
    • Gallipolis, Ohio, United States, 45631
      • Holzer Clinic, Inc
    • Kettering, Ohio, United States, 45429
      • Wells Institute for Health Awareness
    • Newark, Ohio, United States, 43055
      • Newark Physician Associates
    • Perrysburg, Ohio, United States, 43551
      • Daniel G. Williams, Md
    • Zanesville, Ohio, United States, 43701
      • Physician Research, Inc.
  • Oklahoma
    • Bethany, Oklahoma, United States, 73008
      • Gilbert Medical Research, Llc
    • Tulsa, Oklahoma, United States, 74104
      • Tulsa Clinical Research, LLC
    • Yukon, Oklahoma, United States, 73099
      • Integris Family Care Yukon
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Williamette Valley Clinical Studies
  • Pennsylvania
    • Dingmans Ferry, Pennsylvania, United States, 18328
      • Dingmans Medical
    • Fleetwood, Pennsylvania, United States, 19522
      • Integrated Medical Group Pc/Fleetwood Clinical Research
    • Shippensburg, Pennsylvania, United States, 17257
      • Wellmon Family Practice
  • Rhode Island
    • E. Providence, Rhode Island, United States, 02914
      • Safe Harbor Clinical Research
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Southeastern Research Associates, Inc.
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Holston Medical Group
    • Fayetteville, Tennessee, United States, 37334
      • Parkway Medical Group
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
    • Memphis, Tennessee, United States, 38125
      • Southwind Medical Specialists
  • Texas
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes & Endocrine Center
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development
    • Houston, Texas, United States, 77004
      • Endocrine Associates
    • Houston, Texas, United States, 77024
      • Village Family Practice
    • Houston, Texas, United States, 77036
      • Juno Research, LLC.
    • Houston, Texas, United States, 77074
      • Non-Invasive Cardiovascular, Pa
    • Houston, Texas, United States, 77081
      • Excel Clinical Research
    • Midland, Texas, United States, 79707
      • Midland Clinical Research Center
    • New Braunfels, Texas, United States, 78130
      • Hill Country Medical Associates
    • San Antonio, Texas, United States, 78229
      • S.A.M. Clinical Research Center
    • San Antonio, Texas, United States, 78229
      • Covenant Clinical Research, Pa
  • Utah
    • Midvale, Utah, United States, 84047
      • Avastra Clinical Trials
  • Virginia
    • Falls Church, Virginia, United States, 22044
      • Seven Corners Medical Center
    • Virginia Beach, Virginia, United States, 23454
      • Tidewater Integrated Medical Research
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Treatment naive males and females, >= 18 years old and

<= 77 years old, with type 2 diabetes mellitus

• Subjects must have central laboratory pre-randomization hemoglobin A1C >= 7.5 and <= 12.0%
• C-peptide >= 1.0 ng/mL (0.34 nmol/L)
• Body Mass Index <= 45 kg/m2
• Must be able to perform self monitoring of blood glucose

Exclusion Criteria:

• aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3X*upper limit of normal (ULN)
• Serum Total bilirubin >2 mg/dL (34.2 µmol/L)
• Creatinine kinase >3*ULN
• Serum creatinine >= 1.50 mg/dL (133 µmol/L) for male subjects, >= 1.40 mg/dL (124 µmol/L) for female subjects
• Calcium value outside of the central laboratory normal reference range
• Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases
• Urine albumin:creatinine ratio (UACR) >1800 mg/g (203.4 mg/mmol Cr)
• Severe uncontrolled hypertension defined as systolic blood pressure (SBP) >=180 mmHg and/or diastolic blood pressure (DBP) >=110 mmHg
• Hemoglobin >=11.0 g/dL (110 g/L) for men; hemoglobin >=10.0 g/dL (100 g/L) for women
• Positive for hepatitis B surface antigen
• Positive for anti-hepatitis C virus antibody
• History of diabetes insipidus
• History of diabetic ketoacidosis or hyperosmolar nonketotic coma
• Symptoms of poorly controlled diabetes that would preclude participation in this trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin + Metformin XR; Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks	Drug: Dapagliflozin; Tablets, Oral, 10 mg, once daily, 24 weeks; Other Names: Farxiga™; Drug: Metformin XR; Tablets, Oral, up to 2000 mg, once daily, 24 weeks; Other Names: Glucophage®; Drug: Metformin XR; Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks; Other Names: Glucophage®
Experimental: Dapagliflozin + Placebo; Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks. Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.	Drug: Dapagliflozin; Tablets, Oral, 10 mg, once daily, 24 weeks; Other Names: Farxiga™; Drug: metformin HCl Modified Release matching Placebo; Tablets
Active Comparator: Metformin XR + Placebo; Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks	Drug: Metformin XR; Tablets, Oral, up to 2000 mg, once daily, 24 weeks; Other Names: Glucophage®; Drug: Metformin XR; Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks; Other Names: Glucophage®; Drug: dapagliflozin matching Placebo; Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 (Last Observation Carried Forward) - Randomized Treated Participants	Adjusted mean change in HbA1c from baseline at Week 24 (or the last post-baseline measurement prior to Week 24 if no Week 24 assessment was available, ie, last observation carried forward (LOCF) was determined. 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.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (LOCF) - Randomized, Treated Participants	Data after rescue medication was excluded from this analysis. FPG 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, 3, 4, 6, 8, 12, 16, 20, and 24 of the Double-Blind Period.	Week 24
Percent Adjusted for Baseline HbA1c of Participants Achieving a Therapeutic Glycemic Response at Week 24 (LOCF) - Randomized, Treated Participants	Therapeutic glycemic response was defined as HbA1c less than 7.0%. n=Number of participants with HBA1c less than (<) 7 % at Week 24, last observation carried forward (LOCF) while N=number of randomized participants with non-missing baseline and Week 24 (LOCF) values. Percent=n/N and was adjusted for Baseline HbA1c. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.	Week 24
Adjusted Mean Change From Baseline in HbA1C at Week 24 (LOCF) in Participants Whose Baseline HbA1C Category ≥9.0%	HbA1c was measured as percent of hemoglobin by a central laboratory. The population included those randomized, treated participants whose Baseline HbA1c was greater than, equal to (>=) 9.0%. 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.	Week 24
The Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (LOCF) - Randomized, Treated Participants	Adjusted mean change from baseline in total body weight at Week 24 (or the last post-baseline 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 was measured in kilograms (kg). Body weight measurements were obtained during the Qualification and Lead-In Periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the Double-Blind Period.	Week 24
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Discontinuation Due to AEs, During the 12 Week Double Blind Period, Including Data After Rescue - All Treated Participants	Medical Dictionary for Regulatory Activities (MedDRA), version 12.1 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. Treatment-related=having certain, probable, possible, or missing relationship to study drug as per the investigator. Events captured from baseline to last dose plus 4 days for AEs, plus 30 days for SAEs during the Double Blind 12 Week Period. Data after rescue included.	Day 1 of Double Blind Period to end of Week 24 Plus 30 days
Number of Participants With Adverse Events of Special Interest During the 12 Week Double Blind Period - All Treated Participants	Participants with AEs of hypoglycemia, cardiac/vascular disorders, renal impairment or failure, volume depletion (hypotension/dehydration/hypovolemia), fractures, urinary stones, and other reports suggestive of genital infection or urinary tract infection (UTI) were summarized using MedDRA version 13.0. Data after rescue included for all special AEs except hypoglycemia (excluded data after rescue). Major hypoglycemic episode: symptomatic requiring 3rd party assistance due to severe impairment in consciousness or behavior with a glucose value < 54 mg/dL and prompt recovery after glucose/glucagon; Minor: either symptomatic with glucose measurement < 63 mg/dL, regardless of need for 3rd party assistance, or asymptomatic with glucose < 63 mg/dL that does not qualify as major; Other: suggestive but not meeting criteria for major or minor.	Baseline to last dose plus 4 days in 12 Week Double Blind Period
Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure at Week 24 - Treated Participants	Measurements were taken during the Qualification and Lead-In Periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 in the Double Blind Period. Blood pressure values were obtained: after the participant was seated quietly for 5 minutes; at least 8 hours after the last ingestion of caffeine, alcohol, or nicotine; and in the same arm (right or left) consistently through out the study. Systolic and Diastolic pressures were measured in millimeters of mercury (mmHg). Data after rescue were also included. 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.	Week 24
Mean Change From Baseline in Seated Heart Rate at Week 24 - Randomized, Treated Participants	Measurements were taken during the Qualification and Lead-In Periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 in the Double Blind Period. Heart rate values were obtained: after the participant was seated quietly for 5 minutes; at least 8 hours after the last ingestion of caffeine, alcohol, or nicotine; and in the same arm (right or left) consistently throughout the study. Heart rate was measured in beats per minute (bpm). Data after rescue were also included. 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.	Week 24
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 24 (LOCF) - Randomized, Treated Participants	12-Lead electrocardiograms (ECGs) were performed at entry into Lead-In Period Day -7 visit and Week 24/End of treatment visit (last observation carried forward) on participants who were supine. ECGs were assessed by the investigator. Baseline (BL) was Day -7 for this parameter. Data after rescue included.	Week 24
Number of Participants With Marked Laboratory Abnormalities (Not Including Liver Function) in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants	Laboratory samples: Qualification and Lead-In Periods, Day 1, Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of Double-Blind Period. Baseline (BL)=last assessment prior to start of first dose of double-blind study medication. Data after rescue included. Pretreatment (PreRX); grams per deciliter (g/dL); upper limit of normal (ULN); milliequivalent per liter (mEq/L); Units per liter (U/L), blood urea nitrogen (BUN). Marked abnormality Low (High) defined: hemoglobin <6 (>18 females or >20 males) g/dL; hematocrit <20% ( >55% females or >60% males); creatinine (>=1.5*preRX, >=2.5 mg/dL); glucose <54 (>350) mg/dL; creatine kinase (>5*ULN);calcium <7.5 (>=1 mg/dL from ULN and >= 0.5mg/dL from PreRX); sodium <130 or < 120 male/female (>150 mEq/L; potassium <=2.5 (>=6.0) mEq/L; bicarbonate <= 13 mEq/L; inorganic phosphorus: <=1.8 if age 17-65 or <=2.1 if age >=66, (>=5.6 if age 17-65 or >=5.1) mg/dL if age >=66; albumin <=2 (>6) g/dL; urine albumin(alb) / creatinine (creat) ratio (>1800 mg/g)	Baseline to Week 24/end of treatment plus 4 days
Number of Participants With Marked Laboratory Abnormalities in Liver Function in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants	Safety laboratory measurements were obtained during the Qualification and Lead-In Periods and on Day 1 of the Double-Blind Period and at Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24. BL was defined as the last assessment prior to the start of the first dose of the double-blind study medication. Data included from BL up to and including the last day of treatment plus 30 days. Liver function abnormality criteria: FDA Guidance for Industry: Premarketing Clinical Evaluation (July 2009). Data after rescue was also included. Abbreviations: Pretreatment (PreRX), upper limit of normal (ULN); greater than (>) less than (<); Units per liter (U/L), alanine aminotransferase (ALT); aspartate aminotransferase (AST); alkaline phosphatase (ALP). Marked abnormality Low (High) defined: ALP, AST and ALT (>3*ULN); bilirubin (>2*ULN if PreRX <= ULN; >3*ULN if PreRX > ULN); AST or ALT plus (+) bilirubin elevation: AST or ALT >3*ULN and bilirubin >1.5*ULN within 14 days on or after ALT elevation.	Baseline to Week 24/end of treatment plus 30 days

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: March 10, 2009
• First Submitted That Met QC Criteria: March 10, 2009
• First Posted (Estimate): March 11, 2009

Study Record Updates

• Last Update Posted (Estimate): July 7, 2016
• Last Update Submitted That Met QC Criteria: May 30, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Dapagliflozin; Diabetes Mellitus; Metformin; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Pharmacologic Actions; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hypoglycemic Agents
• 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: MB102-034; Eudract #: 2008-007548-33