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

September 11, 2007
May 13, 2014
September 2007
November 2008   (final data collection date for primary outcome measure)
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.
Change from baseline in hemoglobin A1C [ Time Frame: at Week 24 ]
Complete list of historical versions of study NCT00528879 on ClinicalTrials.gov Archive Site
  • 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.
  • Change from baseline in fasting plasma glucose [ Time Frame: at Week 24 ]
  • Proportion of subjects achieving a therapeutic glycemic response, defined as AIC < 7.0% [ Time Frame: at Week 24 ]
  • Change from baseline in total body weight [ Time Frame: at Week 24 ]
  • Change from baseline in fasting plasma glucose [ Time Frame: at Week 1 ]
  • 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.
Not Provided
 
A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled on Metformin Alone
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Type 2 Diabetes
  • 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
  • Placebo Comparator: Placebo + Metformin
    Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks
    Interventions:
    • Drug: Placebo
    • Drug: Metformin
  • 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
    Interventions:
    • Drug: Dapagliflozin
    • Drug: Metformin
  • 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
    Interventions:
    • Drug: Dapagliflozin
    • Drug: Metformin
  • 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
    Interventions:
    • Drug: Dapagliflozin
    • Drug: Placebo
    • Drug: Metformin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
915
May 2010
November 2008   (final data collection date for primary outcome measure)

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
Both
18 Years to 77 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Brazil,   Canada,   Mexico
 
NCT00528879
MB102-014 LT
No
Bristol-Myers Squibb
Bristol-Myers Squibb
AstraZeneca
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP