Clinical trial NCT00528879: A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled on Metformin Alone
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Keywords: Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2007-09-12
Enrollment: 915
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 learn whether dapagliflozin can help reduce blood sugar levels in participants with Type 2 diabetes that is not well controlled on metformin alone. The safety of this treatment will also be studied.


Eligibility criteria: Key Inclusion Criteria

* Males and females, 18 to 77 years old, with type 2 diabetes and inadequate glycemic control
* Participants who have been receiving metformin at a total daily dose ≥1500 mg per day for at least 8 weeks
* C-peptide ≥1.0 ng/mL
* Body mass index ≤45.0 kg/m\^2
* Serum creatinine level \<1.50 mg/dL for men or \<1.40 mg/dL for women.

Key Exclusion Criteria

* Aspartate aminotransferase and/or alanine aminotransferase level \>3.0 times the upper limit of normal
* Serum total bilirubin level \>2 mg/dL
* Creatinine kinase level \>3 times upper limit of normal
* Symptoms of severely uncontrolled diabetes
* Serum creatinine level ≥1.50 mg/dL for men or ≥1.40 mg/dL for women
* Currently unstable or serious cardiovascular, renal, hepatic, hematologic, oncologic, endocrine, psychiatric, or rheumatic diseases

Primary outcomes:
measure: Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
Secondary outcomes:
measure: Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
measure: Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c ≥9.0% at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Change From Baseline in Total Body Weight at Week 24 in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 1
measure: Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [LOCF])
timeFrame: From Baseline to Week 24
Other outcomes:
measure: Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation
timeFrame: From Baseline to end of Long-term Period (Week 102)
measure: Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality
timeFrame: Day 1 to Week 102
measure: Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])
timeFrame: Baseline to Week 102
measure: Mean Changes From Baseline in Seated Systolic Blood Pressure
timeFrame: From Baseline to Week 102
measure: Mean Changes From Baseline in Seated Diastolic Blood Pressure
timeFrame: From Baseline to Week 102
measure: Number of Participants With Orthostatic Hypotension
timeFrame: From Baseline to Week 102
Locations:
city: Tempe
country: United States
facility: Clinical Research Advantage / Desert Clinical Res, Llc
state: Arizona
city: Encino
country: United States
facility: Medical Group Of Encino
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: Los Angeles
country: United States
facility: Randall Shue, D.O.
state: California
city: Northridge
country: United States
facility: Diabetes Medical Center Of California
state: California
city: San Diego
country: United States
facility: Ritchken & First M.D.'S
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Torrance
country: United States
facility: Raikhel, Marina
state: California
city: Colorado Springs
country: United States
facility: Express Care Clinical Res
state: Colorado
city: Denver
country: United States
facility: Denver Internal Medicine
state: Colorado
city: Golden
country: United States
facility: New West Physicians
state: Colorado
city: Altamonte Springs
country: United States
facility: Central Florida Clinical Trials, Inc.
state: Florida
city: Chipley
country: United States
facility: Family Care Associates Of Nw Florida
state: Florida
city: Minneapolis
country: United States
facility: Health Partners Research Foundation
state: Minnesota
city: Chesterfield
country: United States
facility: Woodlake Research
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Alliance Against Diabetes
state: Nevada
city: Morehead City
country: United States
facility: Diabetes & Endocrinology Consultants, Pc
state: North Carolina
city: Newark
country: United States
facility: Newark Physician Associates
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Family Care S. Penn
state: Oklahoma
city: Carlisle
country: United States
facility: Cumberland Valley Endocrinology Center, Llc
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Banksville Medical Pc
state: Pennsylvania
city: Summerville
country: United States
facility: Palmetto Clinical Research
state: South Carolina
city: Taylors
country: United States
facility: Southeastern Research Assoc
state: South Carolina
city: Houston
country: United States
facility: Texas Center For Drug Development, P.A.
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Research Associates, Inc.
state: Texas
city: San Antonio
country: United States
facility: S.A.M. Clinical Research Center
state: Texas
city: Salt Lake City
country: United States
facility: Optimum Clinical Research
state: Utah
city: Spokane
country: United States
facility: Office Of Dr. Gray
state: Washington
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Ciudad Auton.
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Ciudad Auton
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Mar Del Plata
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Zarate
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Villa Carlos Paz
country: Argentina
facility: Local Institution
state: Cordoba
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Local Institution
city: Fortaleza
country: Brazil
facility: Local Institution
state: Ceara
city: Itajuba
country: Brazil
facility: Local Institution
state: Minas Gerais
city: Belem
country: Brazil
facility: Local Institution
state: Para
city: Caxias Do Sul
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Marilia
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Rio De Janeiro
country: Brazil
facility: Local Institution
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: Mount Pearl
country: Canada
facility: Local Institution
state: Newfoundland and Labrador
city: St-John
country: Canada
facility: Local Institution
state: Newfoundland and Labrador
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: Df
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Zapopan
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: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Tampico
country: Mexico
facility: Local Institution
state: Tamaulipas
city: Durango
country: Mexico
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Shah M, Stolbov L, Yakovleva T, Tang W, Sokolov V, Penland RC, Boulton D, Parkinson J. A model-based approach to investigating the relationship between glucose-insulin dynamics and dapagliflozin treatment effect in patients with type 2 diabetes. Diabetes Obes Metab. 2021 Apr;23(4):991-1000. doi: 10.1111/dom.14305. Epub 2021 Jan 25.
citation: Bailey CJ, Del Prato S, Wei C, Reyner D, Saraiva G. Durability of glycaemic control with dapagliflozin, an SGLT2 inhibitor, compared with saxagliptin, a DPP4 inhibitor, in patients with inadequately controlled type 2 diabetes. Diabetes Obes Metab. 2019 Nov;21(11):2564-2569. doi: 10.1111/dom.13841. Epub 2019 Aug 26.
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.
citation: Bailey CJ, Gross JL, Hennicken D, Iqbal N, Mansfield TA, List JF. Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial. BMC Med. 2013 Feb 20;11:43. doi: 10.1186/1741-7015-11-43.
citation: Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet. 2010 Jun 26;375(9733):2223-33. doi: 10.1016/S0140-6736(10)60407-2.