Clinical trial NCT00859898: Study of Dapagliflozin in Combination With Metformin XR to Initiate the Treatment of Type 2 Diabetes
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Dapagliflozin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2009-03-11
Enrollment: 1093
Sex: ALL
Minimum age (years): 18
Maximum age (years): 77
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 (Last Observation Carried Forward) - Randomized Treated Participants
timeFrame: Week 24
Secondary outcomes:
measure: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (LOCF) - Randomized, Treated Participants
timeFrame: Week 24
measure: Percent Adjusted for Baseline HbA1c of Participants Achieving a Therapeutic Glycemic Response at Week 24 (LOCF) - Randomized, Treated Participants
timeFrame: Week 24
measure: Adjusted Mean Change From Baseline in HbA1C at Week 24 (LOCF) in Participants Whose Baseline HbA1C Category ≥9.0%
timeFrame: Week 24
measure: The Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (LOCF) - Randomized, Treated Participants
timeFrame: Week 24
measure: 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
timeFrame: Day 1 of Double Blind Period to end of Week 24 Plus 30 days
measure: Number of Participants With Adverse Events of Special Interest During the 12 Week Double Blind Period - All Treated Participants
timeFrame: Baseline to last dose plus 4 days in 12 Week Double Blind Period
measure: Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure at Week 24 - Treated Participants
timeFrame: Week 24
measure: Mean Change From Baseline in Seated Heart Rate at Week 24 - Randomized, Treated Participants
timeFrame: Week 24
measure: Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 24 (LOCF) - Randomized, Treated Participants
timeFrame: Week 24
measure: 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
timeFrame: Baseline to Week 24/end of treatment plus 4 days
measure: Number of Participants With Marked Laboratory Abnormalities in Liver Function in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants
timeFrame: Baseline to Week 24/end of treatment plus 30 days
Other outcomes:
Locations:
city: Ozark
country: United States
facility: International Institute Of Clinical Research
state: Alabama
city: Tempe
country: United States
facility: Clinical Research Advantage, Inc./Mesa Family Med Ctr, Pc
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Advantage, Inc.
state: Arizona
city: Concord
country: United States
facility: John Muir Physician Network Clinical Research Center
state: California
city: Encinitas
country: United States
facility: Encompass Clinical Research-North Coast
state: California
city: Fountain Valley
country: United States
facility: Southland Clinical Research Center, Inc.
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: Huntington Park
country: United States
facility: Del Rosario Medical Clinic, Inc.
state: California
city: Irvine
country: United States
facility: Irvine Center For Clinical Research, Inc.
state: California
city: Redlands
country: United States
facility: Pacific Sleep Medicine Services (Avastra Clinical Trials)
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Colorado Springs
country: United States
facility: Lynn Institute Of The Rockies
state: Colorado
city: Denver
country: United States
facility: Radiant Research, Inc.
state: Colorado
city: Coral Gables
country: United States
facility: Clinical Therapeutics Corporation
state: Florida
city: Miami
country: United States
facility: Nextphase Clinical Trials, Inc.
state: Florida
city: Miami
country: United States
facility: Baptist Diabetes Associates
state: Florida
city: W Palm Beach
country: United States
facility: Metabolic Research Institute, Inc.
state: Florida
city: Hartwell
country: United States
facility: Lake Hartwell Family Medicine
state: Georgia
city: Perry
country: United States
facility: Middle Georgia Drug Study Center, Llc
state: Georgia
city: Boise
country: United States
facility: Northwest Clinical Trials
state: Idaho
city: Addison
country: United States
facility: Provident Clinical Research
state: Illinois
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Vernon Hills
country: United States
facility: Deerbrook Medical Associates
state: Illinois
city: Indianapolis
country: United States
facility: Physicians Research Group
state: Indiana
city: Kalamazoo
country: United States
facility: Borgess Research Institute
state: Michigan
city: Olive Branch
country: United States
facility: Olive Branch Family Medical Center
state: Mississippi
city: New York
country: United States
facility: Clinilabs, Inc.
state: New York
city: Charlotte
country: United States
facility: Metrolina Medical Research
state: North Carolina
city: Greensboro
country: United States
facility: Pharmquest
state: North Carolina
city: Salisbury
country: United States
facility: Crescent Medical Research
state: North Carolina
city: Canal Fulton
country: United States
facility: Community Health Care, Inc.
state: Ohio
city: Gallipolis
country: United States
facility: Holzer Clinic, Inc
state: Ohio
city: Kettering
country: United States
facility: Wells Institute For Health Awareness
state: Ohio
city: Newark
country: United States
facility: Newark Physician Associates
state: Ohio
city: Perrysburg
country: United States
facility: Daniel G. Williams, Md
state: Ohio
city: Zanesville
country: United States
facility: Physician Research, Inc.
state: Ohio
city: Bethany
country: United States
facility: Gilbert Medical Research, Llc
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Clinical Research, Llc
state: Oklahoma
city: Yukon
country: United States
facility: Integris Family Care Yukon
state: Oklahoma
city: Eugene
country: United States
facility: Williamette Valley Clinical Studies
state: Oregon
city: Dingmans Ferry
country: United States
facility: Dingmans Medical
state: Pennsylvania
city: Fleetwood
country: United States
facility: Integrated Medical Group Pc/Fleetwood Clinical Research
state: Pennsylvania
city: Shippensburg
country: United States
facility: Wellmon Family Practice
state: Pennsylvania
city: E. Providence
country: United States
facility: Safe Harbor Clinical Research
state: Rhode Island
city: Greenville
country: United States
facility: Southeastern Research Associates, Inc.
state: South Carolina
city: Bristol
country: United States
facility: Holston Medical Group
state: Tennessee
city: Fayetteville
country: United States
facility: Parkway Medical Group
state: Tennessee
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Memphis
country: United States
facility: Southwind Medical Specialists
state: Tennessee
city: Dallas
country: United States
facility: Dallas Diabetes & Endocrine Center
state: Texas
city: Houston
country: United States
facility: Endocrine Associates
state: Texas
city: Houston
country: United States
facility: Village Family Practice
state: Texas
city: Houston
country: United States
facility: Juno Research, Llc.
state: Texas
city: Houston
country: United States
facility: Non-Invasive Cardiovascular, Pa
state: Texas
city: Houston
country: United States
facility: Excel Clinical Research
state: Texas
city: Houston
country: United States
facility: Texas Center For Drug Development
state: Texas
city: Midland
country: United States
facility: Midland Clinical Research Center
state: Texas
city: New Braunfels
country: United States
facility: Hill Country Medical Associates
state: Texas
city: San Antonio
country: United States
facility: Covenant Clinical Research, Pa
state: Texas
city: San Antonio
country: United States
facility: S.A.M. Clinical Research Center
state: Texas
city: Midvale
country: United States
facility: Avastra Clinical Trials
state: Utah
city: Falls Church
country: United States
facility: Seven Corners Medical Center
state: Virginia
city: Virginia Beach
country: United States
facility: Tidewater Integrated Medical Research
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Hyderabad
country: India
facility: Local Institution
state: Andhra Pradesh
city: Aminjikarai
country: India
facility: Local Institution
state: Chennai
city: Haryana
country: India
facility: Local Institution
state: Karnal
city: Bangalore
country: India
facility: Local Institution
state: Karnataka
city: Indore
country: India
facility: Local Institution
state: Madhya Pradesh
city: Nagpur
country: India
facility: Local Institution
state: Maharashtra
city: Nagpur
country: India
facility: Local Institution
state: Maharashtra
city: Chennai
country: India
facility: Local Institution
state: Tamilnadu
city: Ghaziabad
country: India
facility: Local Institution
state: Uttar Pradesh
city: Jaipur
country: India
facility: Local Institution
city: Bucheon
country: Korea, Republic of
facility: Local Institution
state: Gyeonggi-Do
city: Goyang-Si
country: Korea, Republic of
facility: Local Institution
state: Gyeonggi-Do
city: Guri-Si
country: Korea, Republic of
facility: Local Institution
state: Gyeonggi-Do
city: Sungnam
country: Korea, Republic of
facility: Local Institution
state: Gyeonggi-Do
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Incheon
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Morelia
country: Mexico
facility: Local Institution
state: Michioacan
city: Cuernavaca
country: Mexico
facility: Local Institution
state: Morelos
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Merida
country: Mexico
facility: Local Institution
state: Yucatan
city: Aguascalientes
country: Mexico
facility: Local Institution
city: Durango
country: Mexico
facility: Local Institution
city: Veracruz
country: Mexico
facility: Local Institution
city: Fajardo
country: Puerto Rico
facility: Local Institution
city: Ponce
country: Puerto Rico
facility: Local Institution
city: Ponce
country: Puerto Rico
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Local Institution
city: Ekaterinaburg
country: Russian Federation
facility: Local Institution
city: Kemerovo
country: Russian Federation
facility: Local Institution
city: Krasnoyarsk
country: Russian Federation
facility: Local Institution
city: Moscov
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Nizhniy Novgorod
country: Russian Federation
facility: Local Institution
city: Nizhniy Novgorod
country: Russian Federation
facility: Local Institution
city: Novosibirsk
country: Russian Federation
facility: Local Institution
city: Novosibirsk
country: Russian Federation
facility: Local Institution
city: Saint Petersburg
country: Russian Federation
facility: Local Institution
city: Saint-Petersburg
country: Russian Federation
facility: Local Institution
city: Samara
country: Russian Federation
facility: Local Institution
city: Saratov
country: Russian Federation
facility: Local Institution
city: Smolensk
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St.Petersburg
country: Russian Federation
facility: Local Institution
city: Tyumen
country: Russian Federation
facility: Local Institution
city: Vladimir
country: Russian Federation
facility: Local Institution
city: Volgograd
country: Russian Federation
facility: Local Institution
city: Voronezh
country: Russian Federation
facility: Local Institution
city: Yaroslavl
country: Russian Federation
facility: Local Institution
city: Yaroslavl
country: Russian Federation
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Kohan DE, Fioretto P, Johnsson K, Parikh S, Ptaszynska A, Ying L. The effect of dapagliflozin on renal function in patients with type 2 diabetes. J Nephrol. 2016 Jun;29(3):391-400. doi: 10.1007/s40620-016-0261-1. Epub 2016 Feb 19.