A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled on Metformin Alone

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00528879
First received: September 11, 2007
Last updated: May 13, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes
Drug: Dapagliflozin
Drug: Placebo
Drug: Metformin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Data after rescue medication was excluded from this analysis. Fasting plasma glucose 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.

  • Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    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. 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.

  • Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.

  • Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c ≥9.0% at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. HbA1c was measured as percent of hemoglobin by a central laboratory. The population included those randomized participants who received treatment and had a 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 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.

  • 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]) [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    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. 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.

  • 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]) [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted for baseline HbA1c. HbA1c was measured as percent of hemoglobin by a central laboratory. 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.

  • Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 1 ] [ Designated as safety issue: No ]
    Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. 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.

  • Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
    Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.


Other Outcome Measures:
  • 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 [ Time Frame: From Baseline to end of Long-term Period (Week 102) ] [ Designated as safety issue: Yes ]
    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. Events captured from baseline to last dose plus 4 days for AEs and plus 30 days for SAEs during the double-blind 12-week period. Data after rescue included.

  • Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality [ Time Frame: Day 1 to Week 102 ] [ Designated as safety issue: Yes ]
    BUN=blood urea nitrogen; preRX=pretreatment; ULN=upper limit of normal; AST=aspartate aminotransferase; ALT=alanine aminotransferase; ALP=alkaline phosphatase. Phosphorus, inorganic (low): ages 17-65 years, ≤1.8 mg/dL; ages≥66 years, ≤2.1 mg/dL. Phosphorus, inorganic (high): ages 17-65 years, ≥5.6 mg/dL; ages≥66 years, ≥5.6 mg/dL. Phosphorus, inorganic (low) ≤1.8 mg/dL if age 17-65 or ≤2.1 mg/dL if age ≥66. Calcium, total (high): ≥1 mg/dL from ULN and ≥0.5 mg/dL from preRx value.

  • Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) [ Time Frame: Baseline to Week 102 ] [ Designated as safety issue: Yes ]
    12-Lead electrocardiograms (ECGs) were performed at entry into lead-in period Day -7 visit and Week 24/dnd of treatment visit (LOCF) on participants who were supine. ECGs were assessed by the investigator. Baseline was Day -7 for this parameter. Data after rescue included.The Week 102 value is the last observation, regardless of rescue prior to Week 102 if no Week 102 measurement was available.

  • Mean Changes From Baseline in Seated Systolic Blood Pressure [ Time Frame: From Baseline to Week 102 ] [ Designated as safety issue: Yes ]
    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. 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.

  • Mean Changes From Baseline in Seated Diastolic Blood Pressure [ Time Frame: From Baseline to Week 102 ] [ Designated as safety issue: Yes ]
    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. 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.

  • Number of Participants With Orthostatic Hypotension [ Time Frame: From Baseline to Week 102 ] [ Designated as safety issue: Yes ]
    Orthostatic hypotension was defined as a decrease from supine to standing blood pressure of >20 mm Hg in systolic blood pressure or >10 mm Hg in diastolic blood pressure.


Enrollment: 915
Study Start Date: September 2007
Study Completion Date: May 2010
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo + Metformin
Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Drug: Placebo
Dapagliflozin-matching placebo administered as tablets orally once daily for up to 102 weeks
Drug: Metformin
Open-label metformin administered as ≥1500 mg per day for up to 102 weeks
Experimental: Dapagliflozin, 2.5 mg + Metformin
Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Drug: Dapagliflozin
Tablets administered orally as a 2.5-, 5-, or 10-mg dose once daily for up to 102 weeks
Other Name: BMS-512148
Drug: Metformin
Open-label metformin administered as ≥1500 mg per day for up to 102 weeks
Experimental: Dapagliflozin, 5 mg + Metformin
Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Drug: Dapagliflozin
Tablets administered orally as a 2.5-, 5-, or 10-mg dose once daily for up to 102 weeks
Other Name: BMS-512148
Drug: Metformin
Open-label metformin administered as ≥1500 mg per day for up to 102 weeks
Experimental: Dapagliflozin, 10 mg + Metformin
Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
Drug: Dapagliflozin
Tablets administered orally as a 2.5-, 5-, or 10-mg dose once daily for up to 102 weeks
Other Name: BMS-512148
Drug: Placebo
Dapagliflozin-matching placebo administered as tablets orally once daily for up to 102 weeks
Drug: Metformin
Open-label metformin administered as ≥1500 mg per day for up to 102 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 77 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00528879

  Hide Study Locations
Locations
United States, Arizona
Clinical Research Advantage / Desert Clinical Res, Llc
Tempe, Arizona, United States, 85282
United States, California
Medical Group Of Encino
Encino, California, United States, 91436
Valley Research
Fresno, California, United States, 93720
Randall Shue, D.O.
Los Angeles, California, United States, 90023
Diabetes Medical Center Of California
Northridge, California, United States, 91325
Ritchken & First M.D.'S
San Diego, California, United States, 92117
Encompass Clinical Research
Spring Valley, California, United States, 91978
Raikhel, Marina
Torrance, California, United States, 90505
United States, Colorado
Express Care Clinical Res
Colorado Springs, Colorado, United States, 80909
Denver Internal Medicine
Denver, Colorado, United States, 80209
New West Physicians
Golden, Colorado, United States, 80401
United States, Florida
Central Florida Clinical Trials, Inc.
Altamonte Springs, Florida, United States, 32701
Family Care Associates Of Nw Florida
Chipley, Florida, United States, 32428
United States, Minnesota
Health Partners Research Foundation
Minneapolis, Minnesota, United States, 56440
United States, Missouri
Woodlake Research
Chesterfield, Missouri, United States, 63017
United States, Nevada
Nevada Alliance Against Diabetes
Las Vegas, Nevada, United States, 89101
United States, North Carolina
Diabetes & Endocrinology Consultants, Pc
Morehead City, North Carolina, United States, 28557
United States, Ohio
Newark Physician Associates
Newark, Ohio, United States, 43055
United States, Oklahoma
Integris Family Care S. Penn
Oklahoma City, Oklahoma, United States, 73159
United States, Pennsylvania
Cumberland Valley Endocrinology Center, Llc
Carlisle, Pennsylvania, United States, 17013
Banksville Medical Pc
Pittsburgh, Pennsylvania, United States, 15216
United States, South Carolina
Palmetto Clinical Research
Summerville, South Carolina, United States, 29485
Southeastern Research Assoc
Taylors, South Carolina, United States, 29687
United States, Texas
Texas Center For Drug Development, P.A.
Houston, Texas, United States, 77081
S.A.M. Clinical Research Center
San Antonio, Texas, United States, 78229
Diabetes & Glandular Disease Research Associates, Inc.
San Antonio, Texas, United States, 78229
United States, Utah
Optimum Clinical Research
Salt Lake City, Utah, United States, 84102
United States, Washington
Office Of Dr. Gray
Spokane, Washington, United States, 99216
Argentina
Local Institution
Capital Federal, Buenos Aires, Argentina, 1429
Local Institution
Capital Federal, Buenos Aires, Argentina, C1425AGC
Local Institution
Capital Federal, Buenos Aires, Argentina, C1056ABJ
Local Institution
Capital Federal, Buenos Aires, Argentina, 1034
Local Institution
Ciudad Auton, Buenos Aires, Argentina, C1408INH
Local Institution
Ciudad Auton., Buenos Aires, Argentina, C1505CWB
Local Institution
Mar Del Plata, Buenos Aires, Argentina, 7600
Local Institution
Zarate, Buenos Aires, Argentina, 2800
Local Institution
Villa Carlos Paz, Cordoba, Argentina, 5152
Local Institution
Buenos Aires, Argentina, 1431
Local Institution
Cordoba, Argentina, 5000
Brazil
Local Institution
Fortaleza, Ceara, Brazil, 60021
Local Institution
Itajuba, Minas Gerais, Brazil, 37502
Local Institution
Belem, Para, Brazil, 66073
Local Institution
Caxias Do Sul, Rio Grande Do Sul, Brazil, 95070
Local Institution
Porto Alegre, Rio Grande Do Sul, Brazil, 90020090
Local Institution
Porto Alegre, Rio Grande Do Sul, Brazil, 90035
Local Institution
Marilia, Sao Paulo, Brazil, 17519
Local Institution
Rio De Janeiro, Brazil, 20211
Canada, Alberta
Local Institution
Calgary, Alberta, Canada, T2R 0X7
Canada, British Columbia
Local Institution
Kelowna, British Columbia, Canada, V1Y 2H4
Canada, Manitoba
Local Institution
Winnipeg, Manitoba, Canada, R3E 3P4
Canada, New Brunswick
Local Institution
Bathurst, New Brunswick, Canada, E2A 4X7
Canada, Newfoundland and Labrador
Local Institution
Mount Pearl, Newfoundland and Labrador, Canada, A1N 1W7
Local Institution
St-John, Newfoundland and Labrador, Canada, A1E 2E2
Canada, Ontario
Local Institution
Sarnia, Ontario, Canada, N7T 4X3
Local Institution
Thornhill, Ontario, Canada, L4J 8L7
Local Institution
Toronto, Ontario, Canada, M9W 4L6
Local Institution
Toronto, Ontario, Canada, M4R 2G4
Canada, Prince Edward Island
Local Institution
Charlottetown, Prince Edward Island, Canada, C1A 5Y9
Canada, Quebec
Local Institution
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
Canada, Saskatchewan
Local Institution
Saskatoon, Saskatchewan, Canada, S7K 7H9
Local Institution
Saskatoon, Saskatchewan, Canada, S7K 3H3
Mexico
Local Institution
Df, Distrito Federal, Mexico, 11800
Local Institution
Guadalajara, Distrito Federal, Mexico, 44670
Local Institution
Zapopan, Distrito Federal, Mexico, 45150
Local Institution
Guadalajara, Jalisco, Mexico, 44650
Local Institution
Guadalajara, Jalisco, Mexico, 44670
Local Institution
Monterrey, Nuevo Leon, Mexico, 64710
Local Institution
Monterrey, Nuevo Leon, Mexico, 64460
Local Institution
Monterrrey, Nuevo Leon, Mexico, 64700
Local Institution
Tampico, Tamaulipas, Mexico, 89109
Local Institution
Durango, Mexico, 64710
Sponsors and Collaborators
Bristol-Myers Squibb
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00528879     History of Changes
Other Study ID Numbers: MB102-014 LT
Study First Received: September 11, 2007
Results First Received: February 6, 2014
Last Updated: May 13, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administración Nacional de Medicamentos Alimentos y Tecnología Médica
Brazil: Ministério da Saúde and Agência Nacional de Vigilância Sanitária (National Health Surveillance Agency)
Canada: Health Canada
Mexico: Federal Commission for Protection Against Health Risks
Russia: Ministry of Public Health and Social Development of Russian Federation and Ethic Committee of Federal Supervision Service for Public Health and Social Affairs

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014