Clinical trial NCT00528372: A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled With Diet and Exercise
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2007-09-12
Enrollment: 1067
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 purpose of this clinical research study is to determine whether dapagliflozin can improve (decrease) blood glucose values in patients with Type 2 diabetes who have never been treated with medication or have been taking medication for less than 24 weeks since their original diabetes diagnosis. The safety of this treatment will also be studied.

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

Eligibility criteria: 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

Primary outcomes:
measure: Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1C (HbA1c) (Last Observation Carried Forward [LOCF]): Group 1
timeFrame: Baseline to Week 24 (end of Short-term Period)
measure: Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) (Last Observation Carried Forward [LOCF]): Group 2
timeFrame: Baseline to Week 24 (end of Short-term Period)
Secondary outcomes:
measure: Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 1
timeFrame: Baseline to Week 24 (end of Short-term Period)
measure: Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 2
timeFrame: Baseline to Week 24 (end of Short-term Period)
measure: Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 1
timeFrame: From Baseline to Week 24 (end of Short-term Period)
measure: Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 2
timeFrame: From Baseline to Week 24 (end of Short-term Period)
measure: Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 1
timeFrame: Baseline to Week 1 (end of Short-term Period)
measure: Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 2
timeFrame: Baseline to Week 1
measure: Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1c] <7.0%) at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: Baseline to Week 24 (end of Short-term Period)
measure: Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) in Patients With Baseline HbA1c ≥9.0% (Last Observation Carried Forward [LOCF])
timeFrame: Baseline to Week 24 (end of Short-term Period)
measure: 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])
timeFrame: Baseline to Week 24 (end of Short-term Period)
measure: Adjusted Percentage of Participants Who Achieved Hemoglobin A1c [HbA1c] ≤6.5% (Last Observation Carried Forward [LOCF])
timeFrame: Baseline to Week 24 (end of Short-term Period)
measure: 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)
timeFrame: Baseline to Week 24 (end of Short-term Period)
measure: 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)
timeFrame: Day 1 to Week 102 (end of Long-term Period) + 30 days
measure: Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Laboratory Abnormality (Short-term and Long-term Periods)
timeFrame: Baseline to Week 102 (end of Long-term Period)
measure: Number of Participants With Elevated Levels of Liver Enzymes on Laboratory Test Results (Short-term and Long-term Periods)
timeFrame: Day 1 to Week 102 (end of Long-term Period)
measure: Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Findings (Last Observation Carried Forward {LOCF])
timeFrame: Baseline to Week 24 (end of Short-term Period)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: 43rd Medical Associates, P.C.
state: Arizona
city: Tempe
country: United States
facility: Clin Res Advantage, Inc/East Valley Family Physicians, Plc
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Advantage, Inc
state: Arizona
city: Fresno
country: United States
facility: Valley Research
state: California
city: Los Gatos
country: United States
facility: Cherlin, Richard
state: California
city: San Diego
country: United States
facility: Ritchken & First M.D.'S
state: California
city: Torrance
country: United States
facility: Torrance Clinical Research
state: California
city: Aurora
country: United States
facility: Aurora Family Medicine Center, P.C.
state: Colorado
city: Colorado Springs
country: United States
facility: Expresscare Clinical Research
state: Colorado
city: Denver
country: United States
facility: Center For Internal Medicine
state: Colorado
city: Denver
country: United States
facility: Denver Internal Medicine Group
state: Colorado
city: Altamonte Springs
country: United States
facility: Central Florida Clinical Trials
state: Florida
city: Chipley
country: United States
facility: Family Care Associates
state: Florida
city: Jacksonville
country: United States
facility: Westside Center For Clinical Research
state: Florida
city: Marianna
country: United States
facility: Panhandle Family Care Associates
state: Florida
city: Slidell
country: United States
facility: Louisiana Heart Center
state: Louisiana
city: Rolling Fork
country: United States
facility: Jackson, Danny W.
state: Mississippi
city: Chesterfield
country: United States
facility: Woodlake Research
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Alliance Against Diabetes
state: Nevada
city: New Hartford
country: United States
facility: Slocum-Dickson Medical Group, Pllc
state: New York
city: Syracuse
country: United States
facility: Internist Associates Of Central New York, P. C.
state: New York
city: West Seneca
country: United States
facility: Southgate Medical Group
state: New York
city: Dayton
country: United States
facility: Providence Health Partners
state: Ohio
city: Newark
country: United States
facility: Newark Physician Associates
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: Yukon
country: United States
facility: Integris Family Care Yukon
state: Oklahoma
city: Pittsburgh
country: United States
facility: Banksville Medical, Pc
state: Pennsylvania
city: Taylors
country: United States
facility: Southeastern Research Associates, Inc.
state: South Carolina
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Houston
country: United States
facility: Village Family Practice
state: Texas
city: San Antonio
country: United States
facility: Abbott Clinical Research Group, Inc.
state: Texas
city: San Antonio
country: United States
facility: Sam Clinical Research Center
state: Texas
city: Bountiful
country: United States
facility: Taylor/Wade Medical
state: Utah
city: Salt Lake City
country: United States
facility: Optimum Clinical Research, Inc.
state: Utah
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc
state: Utah
city: Virginia Beach
country: United States
facility: Tidewater Integrated Medical Research
state: Virginia
city: Spokane
country: United States
facility: William L. Gray, Md
state: Washington
city: Calgary
country: Canada
facility: Local Institution
state: Alberta
city: Kelowna
country: Canada
facility: Local Institution
state: British Columbia
city: Winnipeg
country: Canada
facility: Local Institution
state: Manitoba
city: Bathurst
country: Canada
facility: Local Institution
state: New Brunswick
city: Moncton
country: Canada
facility: Local Institution
state: New Brunswick
city: Mount Pearl
country: Canada
facility: Local Institution
state: Newfoundland and Labrador
city: St-John
country: Canada
facility: Local Institution
state: Newfoundland and Labrador
city: St. John'S
country: Canada
facility: Local Institution
state: Newfoundland and Labrador
city: Oakville
country: Canada
facility: Local Institution
state: Ontario
city: Sarnia
country: Canada
facility: Local Institution
state: Ontario
city: Thornhill
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Charlottetown
country: Canada
facility: Local Institution
state: Prince Edward Island
city: Drummondville
country: Canada
facility: Local Institution
state: Quebec
city: Granby
country: Canada
facility: Local Institution
state: Quebec
city: L'Ancienne Lorette
country: Canada
facility: Local Institution
state: Quebec
city: Mirabel
country: Canada
facility: Local Institution
state: Quebec
city: St-Leonard
country: Canada
facility: Local Institution
state: Quebec
city: Saskatoon
country: Canada
facility: Local Institution
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Local Institution
state: Saskatchewan
city: Tijuana
country: Mexico
facility: Local Institution
state: Baja California
city: Guadalajara
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico, D. F.
country: Mexico
facility: Local Institution
state: Distrito Federal
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: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrrey
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: Kursk
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Saint-Petersburg
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: Yaroslaval
country: Russian Federation
facility: Local Institution
Study officials:
affiliation: AstraZeneca
name: Anna Maria Langkilde
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
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.