A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled With Diet and Exercise
- Conditions
- Type 2 Diabetes
- Interventions
- Registration Number
- NCT00528372
- Lead Sponsor
- AstraZeneca
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1067
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1: Dapagliflozin, 2.5 mg AM Metformin Participants with hemoglobin A1c (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Group 1: Dapagliflozin, 10 mg AM Metformin Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Group 1: Dapagliflozin 2.5 mg PM Dapagliflozin Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Group 1: Dapagliflozin, 10 mg PM Dapagliflozin Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Group 2: Dapagliflozin, 5 mg AM Metformin Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Group 1: Dapagliflozin placebo AM & PM Dapagliflozin placebo Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Group 1: Dapagliflozin, 2.5 mg AM Dapagliflozin Participants with hemoglobin A1c (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Group 1: Dapagliflozin, 10 mg AM Dapagliflozin Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Group 1: Dapagliflozin 2.5 mg PM Metformin Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Group 1: Dapagliflozin, 5 mg PM Dapagliflozin Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Group 1: Dapagliflozin, 5 mg PM Metformin Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Group 1: Dapagliflozin, 10 mg PM Metformin Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Group 2: Dapagliflozin, 5 mg AM Dapagliflozin Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Group 2: Dapagliflozin, 10 mg AM Dapagliflozin Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Group 1: Dapagliflozin placebo AM & PM Metformin Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Group 1: Dapaglifozon, 5 mg AM Dapagliflozin Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Group 2: Dapagliflozin, 10 mg AM Metformin Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Group 1: Dapaglifozon, 5 mg AM Metformin Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks.
- Primary Outcome Measures
Name Time Method Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1C (HbA1c) (Last Observation Carried Forward [LOCF]): Group 1 Baseline to Week 24 (end of Short-term Period) HbA1c was measured 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. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Evening dosing groups were summarized as exploratory endpoints.
Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) (Last Observation Carried Forward [LOCF]): Group 2 Baseline to Week 24 (end of Short-term Period) HbA1c was measured 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. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Group 2 (patients with enrollment baseline HbA1c \>10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included.
- Secondary Outcome Measures
Name Time Method Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Laboratory Abnormality (Short-term and Long-term Periods) Baseline to Week 102 (end of Long-term Period) Baseline was defined as the last assessment prior to the start of the first dose of the double-blind study medication. Data included from baseline up to and including the last day of treatment plus 4 days. Data after rescue were also included. ULN=upper limit of normal; preRX=pretreatment. Phosphorus, inorganic (high) defined as \>=5.6 mg/dL for ages 17-65 years or \>=5.1 mg/dL for ages \>=66.
Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 1 From Baseline to Week 24 (end of Short-term Period) Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. 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.
Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 2 From Baseline to Week 24 (end of Short-term Period) Secondary endpoints were tested using a 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.Group 2 (patients with enrollment baseline HbA1c \>10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included.
Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 1 Baseline to Week 24 (end of Short-term Period) Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized in secondary efficacy analyses. 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. If no Week 24 assessment was available, glucose levels were recorded from the last postbaseline measurement prior to Week 24. For rescued participants, measurements obtained after initiation of rescue medication was not considered in calculating the endpoint.
Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Findings (Last Observation Carried Forward {LOCF]) Baseline to Week 24 (end of Short-term Period) 12-Lead ECGs were performed at entry into lead-in period Day -7 visit and Week 24/end of treatment visit (LOCF) on participants who were supine. ECGs were assessed by the investigator. Baseline was Day -7 for this parameter, and data after rescue were included.The Week 102 value is the last observation, regardless of rescue prior to Week 102 if no Week 102 measurement was available. Group 2 (patients with enrollment baseline HbA1c \>10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.
Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 1 Baseline to Week 1 (end of Short-term Period) Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. 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 Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) in Patients With Baseline HbA1c ≥9.0% (Last Observation Carried Forward [LOCF]) Baseline to Week 24 (end of Short-term Period) Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. HbA1c was measured as % of hemoglobin by a central laboratory. The population included randomized patients who received treatment and had 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 double-blind study drug. In cases where time of the first dose or 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 drug. Group 2 (patients with enrollment baseline HbA1c \>10% and ≤2%) was considered exploratory, included to obtain initial data. No comparator arm was included. Thus, only key safety and efficacy analyses were performed in Group 2.
Adjusted Percentage of Participants Who Achieved Hemoglobin A1c [HbA1c] ≤6.5% (Last Observation Carried Forward [LOCF]) Baseline to Week 24 (end of Short-term Period) Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. Group 2 (patients with enrollment baseline HbA1c \>10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.
Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 2 Baseline to Week 24 (end of Short-term Period) Group 2 was an exploratory group, included to obtain initial efficacy and safety data. No comparator arm was included. Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. 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. If no Week 24 assessment was available, glucose levels were recorded from the last postbaseline measurement prior to Week 24. For rescued participants, measurements obtained after initiation of rescue medication was not considered in calculating the endpoint.
Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 2 Baseline to Week 1 Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. 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 a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1c] <7.0%) at Week 24 (Last Observation Carried Forward [LOCF]) Baseline to Week 24 (end of Short-term Period) Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Therapeutic glycemic response is defined as HbA1c \<7.0%. Data after rescue medication was excluded from this analysis. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. Group 2 (patients with enrollment baseline HbA1c \>10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.
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]) Baseline to Week 24 (end of Short-term Period) Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. 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. Group 2 (patients with enrollment baseline HbA1c \>10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.
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) Baseline to Week 24 (end of Short-term Period) 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. Group 2 (patients with enrollment baseline HbA1c \>10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.
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) Day 1 to Week 102 (end of Long-term Period) + 30 days 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. Includes non-SAEs and hypoglycemia with onset on or after the first date/time of double-blind treatment and on or prior to the last day of short-term plus long-term treatment plus 4 days. Includes SAEs with onset on or after the first date/time of double-blind treatment and on or prior to the last day of short-term plus long-term treatment plus 30 days.
Number of Participants With Elevated Levels of Liver Enzymes on Laboratory Test Results (Short-term and Long-term Periods) Day 1 to Week 102 (end of Long-term Period) Data after rescue was included. AST=aspartate aminotransferase; ALT=alanine aminotransferase; ALP=alkaline phosphatase. Group 2 (patients with enrollment baseline HbA1c \>10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.
Trial Locations
- Locations (39)
Banksville Medical, Pc
🇺🇸Pittsburgh, Pennsylvania, United States
Ritchken & First M.D.'S
🇺🇸San Diego, California, United States
Village Family Practice
🇺🇸Houston, Texas, United States
Expresscare Clinical Research
🇺🇸Colorado Springs, Colorado, United States
Abbott Clinical Research Group, Inc.
🇺🇸San Antonio, Texas, United States
Sam Clinical Research Center
🇺🇸San Antonio, Texas, United States
Optimum Clinical Research, Inc.
🇺🇸Salt Lake City, Utah, United States
J. Lewis Research, Inc
🇺🇸Salt Lake City, Utah, United States
Family Care Associates
🇺🇸Chipley, Florida, United States
Southeastern Research Associates, Inc.
🇺🇸Taylors, South Carolina, United States
Clinical Research Advantage, Inc
🇺🇸Tempe, Arizona, United States
43rd Medical Associates, P.C.
🇺🇸Phoenix, Arizona, United States
Valley Research
🇺🇸Fresno, California, United States
Woodlake Research
🇺🇸Chesterfield, Missouri, United States
Cherlin, Richard
🇺🇸Los Gatos, California, United States
Nevada Alliance Against Diabetes
🇺🇸Las Vegas, Nevada, United States
Central Florida Clinical Trials
🇺🇸Altamonte Springs, Florida, United States
Providence Health Partners
🇺🇸Dayton, Ohio, United States
Holston Medical Group
🇺🇸Kingsport, Tennessee, United States
William L. Gray, Md
🇺🇸Spokane, Washington, United States
Taylor/Wade Medical
🇺🇸Bountiful, Utah, United States
Gilbert Medical Research, Llc
🇺🇸Bethany, Oklahoma, United States
Local Institution
🇷🇺Yaroslaval, Russian Federation
Aurora Family Medicine Center, P.C.
🇺🇸Aurora, Colorado, United States
Center For Internal Medicine
🇺🇸Denver, Colorado, United States
Denver Internal Medicine Group
🇺🇸Denver, Colorado, United States
Tidewater Integrated Medical Research
🇺🇸Virginia Beach, Virginia, United States
Internist Associates Of Central New York, P. C.
🇺🇸Syracuse, New York, United States
Torrance Clinical Research
🇺🇸Torrance, California, United States
Southgate Medical Group
🇺🇸West Seneca, New York, United States
Integris Family Care Yukon
🇺🇸Yukon, Oklahoma, United States
Newark Physician Associates
🇺🇸Newark, Ohio, United States
Slocum-Dickson Medical Group, Pllc
🇺🇸New Hartford, New York, United States
Physician Research, Inc.
🇺🇸Zanesville, Ohio, United States
Westside Center For Clinical Research
🇺🇸Jacksonville, Florida, United States
Louisiana Heart Center
🇺🇸Slidell, Louisiana, United States
Clin Res Advantage, Inc/East Valley Family Physicians, Plc
🇺🇸Tempe, Arizona, United States
Jackson, Danny W.
🇺🇸Rolling Fork, Mississippi, United States
Panhandle Family Care Associates
🇺🇸Marianna, Florida, United States