A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled With Diet and Exercise
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT00528372
Collaborator
Bristol-Myers Squibb (Industry)
1,067
78
9
34
13.7
0.4
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1067 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, 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 as Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise
Study Start Date
:
Sep 1, 2007
Actual Primary Completion Date
:
Feb 1, 2009
Actual Study Completion Date
:
Jul 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group 1: Dapagliflozin, 2.5 mg AM Participants with hemoglobin A1c (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. |
Drug: Dapagliflozin
Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks
Other Names:
Drug: Metformin
Other Names:
|
| Experimental: Group 1: Dapagliflozin, 10 mg AM Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. |
Drug: Dapagliflozin
Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks
Other Names:
Drug: Metformin
Other Names:
|
| Experimental: Group 1: Dapagliflozin 2.5 mg PM Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. |
Drug: Dapagliflozin
Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks
Other Names:
Drug: Metformin
Other Names:
|
| Experimental: Group 1: Dapagliflozin, 5 mg PM Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. |
Drug: Dapagliflozin
Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks
Other Names:
Drug: Metformin
Other Names:
|
| Experimental: Group 1: Dapagliflozin, 10 mg PM Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. |
Drug: Dapagliflozin
Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks
Other Names:
Drug: Metformin
Other Names:
|
| Experimental: Group 2: Dapagliflozin, 5 mg AM Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. |
Drug: Dapagliflozin
Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks
Other Names:
Drug: Metformin
Other Names:
|
| Experimental: Group 2: Dapagliflozin, 10 mg AM Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. |
Drug: Dapagliflozin
Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks
Other Names:
Drug: Metformin
Other Names:
|
| Experimental: Group 1: Dapagliflozin placebo AM & PM Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. |
Drug: Dapagliflozin placebo
Tablets, oral, 0 mg, once daily in the morning or evening for up to 102 weeks
Drug: Metformin
Other Names:
|
| Experimental: Group 1: Dapaglifozon, 5 mg AM Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. |
Drug: Dapagliflozin
Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks
Other Names:
Drug: Metformin
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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 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 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 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 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 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 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 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 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 77 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 43rd Medical Associates, P.C. | Phoenix | Arizona | United States | 85051 |
| 2 | Clin Res Advantage, Inc/East Valley Family Physicians, Plc | Tempe | Arizona | United States | 85282 |
| 3 | Clinical Research Advantage, Inc | Tempe | Arizona | United States | 85282 |
| 4 | Valley Research | Fresno | California | United States | 93720 |
| 5 | Cherlin, Richard | Los Gatos | California | United States | 95032 |
| 6 | Ritchken & First M.D.'S | San Diego | California | United States | 92117 |
| 7 | Torrance Clinical Research | Torrance | California | United States | 90717 |
| 8 | Aurora Family Medicine Center, P.C. | Aurora | Colorado | United States | 80012 |
| 9 | Expresscare Clinical Research | Colorado Springs | Colorado | United States | 80909 |
| 10 | Center For Internal Medicine | Denver | Colorado | United States | 80209 |
| 11 | Denver Internal Medicine Group | Denver | Colorado | United States | 80209 |
| 12 | Central Florida Clinical Trials | Altamonte Springs | Florida | United States | 32701 |
| 13 | Family Care Associates | Chipley | Florida | United States | 32428 |
| 14 | Westside Center For Clinical Research | Jacksonville | Florida | United States | 32205 |
| 15 | Panhandle Family Care Associates | Marianna | Florida | United States | 32446 |
| 16 | Louisiana Heart Center | Slidell | Louisiana | United States | 70458 |
| 17 | Jackson, Danny W. | Rolling Fork | Mississippi | United States | 39159 |
| 18 | Woodlake Research | Chesterfield | Missouri | United States | 63017 |
| 19 | Nevada Alliance Against Diabetes | Las Vegas | Nevada | United States | 89101 |
| 20 | Slocum-Dickson Medical Group, Pllc | New Hartford | New York | United States | 13413 |
| 21 | Internist Associates Of Central New York, P. C. | Syracuse | New York | United States | 13210 |
| 22 | Southgate Medical Group | West Seneca | New York | United States | 14224 |
| 23 | Providence Health Partners | Dayton | Ohio | United States | 45439 |
| 24 | Newark Physician Associates | Newark | Ohio | United States | 43055 |
| 25 | Physician Research, Inc. | Zanesville | Ohio | United States | 43701 |
| 26 | Gilbert Medical Research, Llc | Bethany | Oklahoma | United States | 73008 |
| 27 | Integris Family Care Yukon | Yukon | Oklahoma | United States | 73109 |
| 28 | Banksville Medical, Pc | Pittsburgh | Pennsylvania | United States | 15216 |
| 29 | Southeastern Research Associates, Inc. | Taylors | South Carolina | United States | 29687 |
| 30 | Holston Medical Group | Kingsport | Tennessee | United States | 37660 |
| 31 | Village Family Practice | Houston | Texas | United States | 77024 |
| 32 | Abbott Clinical Research Group, Inc. | San Antonio | Texas | United States | 78224 |
| 33 | Sam Clinical Research Center | San Antonio | Texas | United States | 78229 |
| 34 | Taylor/Wade Medical | Bountiful | Utah | United States | 84010 |
| 35 | Optimum Clinical Research, Inc. | Salt Lake City | Utah | United States | 84102 |
| 36 | J. Lewis Research, Inc | Salt Lake City | Utah | United States | 84121 |
| 37 | Tidewater Integrated Medical Research | Virginia Beach | Virginia | United States | 23454 |
| 38 | William L. Gray, Md | Spokane | Washington | United States | 99216 |
| 39 | Local Institution | Calgary | Alberta | Canada | T2R 0X7 |
| 40 | Local Institution | Kelowna | British Columbia | Canada | V1Y 2H4 |
| 41 | Local Institution | Winnipeg | Manitoba | Canada | R3E 3P4 |
| 42 | Local Institution | Bathurst | New Brunswick | Canada | E2A 4X7 |
| 43 | Local Institution | Moncton | New Brunswick | Canada | E1G 1A7 |
| 44 | Local Institution | Mount Pearl | Newfoundland and Labrador | Canada | A1N 1W7 |
| 45 | Local Institution | St-John | Newfoundland and Labrador | Canada | A1E 2E2 |
| 46 | Local Institution | St. John'S | Newfoundland and Labrador | Canada | A1A 3R5 |
| 47 | Local Institution | Oakville | Ontario | Canada | L6H 3P1 |
| 48 | Local Institution | Sarnia | Ontario | Canada | N7T 4X3 |
| 49 | Local Institution | Thornhill | Ontario | Canada | L4J 8L7 |
| 50 | Local Institution | Toronto | Ontario | Canada | M4R 2G4 |
| 51 | Local Institution | Toronto | Ontario | Canada | M9W 4L6 |
| 52 | Local Institution | Charlottetown | Prince Edward Island | Canada | C1A 5Y9 |
| 53 | Local Institution | Drummondville | Quebec | Canada | J2B 7T1 |
| 54 | Local Institution | Granby | Quebec | Canada | J2G 8Z9 |
| 55 | Local Institution | L'Ancienne Lorette | Quebec | Canada | G2E 2X1 |
| 56 | Local Institution | Mirabel | Quebec | Canada | J7J 2K8 |
| 57 | Local Institution | St-Leonard | Quebec | Canada | H1S 3A9 |
| 58 | Local Institution | Saskatoon | Saskatchewan | Canada | S7K 3H3 |
| 59 | Local Institution | Saskatoon | Saskatchewan | Canada | S7K 7H9 |
| 60 | Local Institution | Tijuana | Baja California | Mexico | 22320 |
| 61 | Local Institution | Guadalajara | Distrito Federal | Mexico | 44670 |
| 62 | Local Institution | Mexico, D. F. | Distrito Federal | Mexico | 06726 |
| 63 | Local Institution | Guadalajara | Jalisco | Mexico | 44100 |
| 64 | Local Institution | Guadalajara | Jalisco | Mexico | 44600 |
| 65 | Local Institution | Guadalajara | Jalisco | Mexico | 44680 |
| 66 | Local Institution | Morelia | Michioacan | Mexico | 58070 |
| 67 | Local Institution | Monterrey | Nuevo Leon | Mexico | 64060 |
| 68 | Local Institution | Monterrrey | Nuevo Leon | Mexico | 64700 |
| 69 | Local Institution | Merida | Yucatan | Mexico | 97070 |
| 70 | Local Institution | Aguascalientes | Mexico | 20230 | |
| 71 | Local Institution | Durango | Mexico | 34000 | |
| 72 | Local Institution | Kursk | Russian Federation | 305035 | |
| 73 | Local Institution | Moscow | Russian Federation | 115093 | |
| 74 | Local Institution | Saint-Petersburg | Russian Federation | 191015 | |
| 75 | Local Institution | Smolensk | Russian Federation | 214019 | |
| 76 | Local Institution | St. Petersburg | Russian Federation | 195257 | |
| 77 | Local Institution | St.Petersburg | Russian Federation | 195112 | |
| 78 | Local Institution | Yaroslaval | Russian Federation | 150003 |
Sponsors and Collaborators
- AstraZeneca
- Bristol-Myers Squibb
Investigators
- Study Director: Anna Maria Langkilde, AstraZeneca
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00528372
Other Study ID Numbers:
- MB102-013 LT
First Posted:
Sep 12, 2007
Last Update Posted:
Oct 20, 2015
Last Verified:
Sep 1, 2015
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Of 1067 participants enrolled, 558 received treatment in the Short-term Period. Of those 558 participants, 469 entered the Long-term Period. |
| Arm/Group Title | Group 1: Dapagliflozin Placebo | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM | Group 2: Dapagliflozin, 5 mg AM | Group 2: Dapagliflozin, 10 mg AM |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Period Title: Short-term (ST) Period (Day 1-Week 24) | |||||||||
| STARTED | 75 | 65 | 64 | 70 | 67 | 68 | 76 | 34 | 39 |
| COMPLETED | 63 | 60 | 52 | 57 | 58 | 57 | 65 | 28 | 34 |
| NOT COMPLETED | 12 | 5 | 12 | 13 | 9 | 11 | 11 | 6 | 5 |
| Period Title: Short-term (ST) Period (Day 1-Week 24) | |||||||||
| STARTED | 62 | 59 | 51 | 56 | 58 | 57 | 65 | 28 | 33 |
| COMPLETED | 42 | 40 | 43 | 42 | 37 | 42 | 48 | 22 | 27 |
| NOT COMPLETED | 20 | 19 | 8 | 14 | 21 | 15 | 17 | 6 | 6 |
Baseline Characteristics
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM | Group 2: Dapagliflozin, 5 mg AM | Group 2: Dapagliflozin, 10 mg AM | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Total of all reporting groups |
| Overall Participants | 75 | 65 | 64 | 70 | 67 | 68 | 76 | 34 | 39 | 558 |
| Age, Customized (Number) [Number] | ||||||||||
| <65 years |
66
88%
|
54
83.1%
|
54
84.4%
|
66
94.3%
|
52
77.6%
|
53
77.9%
|
72
94.7%
|
34
100%
|
36
92.3%
|
487
87.3%
|
| ≥65 and <75 |
8
10.7%
|
11
16.9%
|
10
15.6%
|
4
5.7%
|
15
22.4%
|
12
17.6%
|
4
5.3%
|
0
0%
|
2
5.1%
|
66
11.8%
|
| ≥75 |
1
1.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
4.4%
|
0
0%
|
0
0%
|
1
2.6%
|
5
0.9%
|
| Sex: Female, Male (Count of Participants) | ||||||||||
| Female |
44
58.7%
|
29
44.6%
|
33
51.6%
|
36
51.4%
|
38
56.7%
|
39
57.4%
|
37
48.7%
|
10
29.4%
|
16
41%
|
282
50.5%
|
| Male |
31
41.3%
|
36
55.4%
|
31
48.4%
|
34
48.6%
|
29
43.3%
|
29
42.6%
|
39
51.3%
|
24
70.6%
|
23
59%
|
276
49.5%
|
| Race/Ethnicity, Customized (Number) [Number] | ||||||||||
| White |
71
94.7%
|
63
96.9%
|
61
95.3%
|
63
90%
|
65
97%
|
65
95.6%
|
72
94.7%
|
31
91.2%
|
38
97.4%
|
529
94.8%
|
| Black/African American |
2
2.7%
|
0
0%
|
1
1.6%
|
2
2.9%
|
1
1.5%
|
1
1.5%
|
2
2.6%
|
1
2.9%
|
0
0%
|
10
1.8%
|
| American Indian/Alaskan Native |
0
0%
|
0
0%
|
0
0%
|
1
1.4%
|
0
0%
|
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
2
0.4%
|
| Asian |
2
2.7%
|
2
3.1%
|
1
1.6%
|
3
4.3%
|
1
1.5%
|
0
0%
|
1
1.3%
|
1
2.9%
|
1
2.6%
|
12
2.2%
|
| Native Hawaiian/Other Pacific Islanders |
0
0%
|
0
0%
|
0
0%
|
1
1.4%
|
0
0%
|
0
0%
|
1
1.3%
|
1
2.9%
|
0
0%
|
3
0.5%
|
| Other |
0
0%
|
0
0%
|
1
1.6%
|
0
0%
|
0
0%
|
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
2
0.4%
|
| Not reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1C (HbA1c) (Last Observation Carried Forward [LOCF]): Group 1 |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 24 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with nonmissing baseline and Week 24 LOCF values |
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 72 | 64 | 61 | 65 | 62 | 63 | 73 |
| Mean (Standard Error) [Percent] |
-0.23
(0.1044)
|
-0.58
(0.1107)
|
-0.77
(0.1134)
|
-0.89
(0.1099)
|
-0.83
(0.1125)
|
-0.79
(0.1117)
|
-0.79
(0.1037)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0207 |
| Comments | Tested at alpha=0.019, applying the Dunnett adjustment | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.35 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1522 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | Tested at alpha=0.019, applying the Dunnett adjustment | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | -0.54 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1541 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Tested at alpha=0.019, applying the Dunnett adjustment | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | -0.66 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1518 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -0.61 | |
| Confidence Interval |
(2-Sided) 95% -0.91 to -0.30 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1536 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -0.56 | |
| Confidence Interval |
(2-Sided) 95% -0.86 to -0.26 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1527 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -0.56 | |
| Confidence Interval |
(2-Sided) 95% -0.85 to -0.27 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1474 |
|
| Estimation Comments | ||
| Title | Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 1 |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 24 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with nonmissing baseline and Week 24 LOCF values |
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 75 | 65 | 64 | 70 | 67 | 66 | 73 |
| Mean (Standard Error) [mg/dL] |
-4.1
(3.906)
|
-15.2
(4.196)
|
-24.1
(4.298)
|
-28.8
(4.046)
|
-25.6
(4.132)
|
-27.3
(4.170)
|
-29.6
(3.964)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -11.1 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.734 |
|
| Estimation Comments | Week 24 | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | Statistically significant according to hierarchical testing procedure (p<0.05) | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -19.9 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.806 |
|
| Estimation Comments | Week 24 | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Statistically significant according to hierarchical testing procedure (p<0.05) | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -24.7 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.626 |
|
| Estimation Comments | Week 24 | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -21.5 | |
| Confidence Interval |
(2-Sided) 95% -32.6 to -10.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.686 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -23.3 | |
| Confidence Interval |
(2-Sided) 95% -34.4 to -12.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.711 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -25.5 | |
| Confidence Interval |
(2-Sided) 95% -36.4 to -14.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 5.567 |
|
| Estimation Comments | ||
| Title | Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 2 |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 24 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with HbA1c ≥10.1% and ≤12% at enrollment and nonmissing baseline and Week 24 LOCF values |
| Arm/Group Title | Group 2: Dapagliflozin, 5 mg AM | Group 2: Dapagliflozin, 10 mg AM |
|---|---|---|
| Arm/Group Description | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 25 | 32 |
| Mean (Standard Deviation) [mg/dL] |
-77.
(53.39)
|
-84.3
(61.01)
|
| Title | Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 1 |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to Week 24 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with nonmissing baseline and Week 24 values |
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 75 | 65 | 62 | 69 | 67 | 66 | 74 |
| Mean (Standard Error) [Kilograms] |
-2.19
(0.4297)
|
-3.25
(0.4615)
|
-2.83
(0.4731)
|
-3.16
(0.4493)
|
-3.82
(0.4548)
|
-3.55
(0.4582)
|
-3.05
(0.4329)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.06 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6307 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3101 |
| Comments | Tested following a sequential testing procedure at alpha=0.05. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.65 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6388 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1189 |
| Comments | Tested following a sequential testing procedure at alpha=0.05. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.97 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6223 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -1.63 | |
| Confidence Interval |
(2-Sided) 95% -2.86 to -0.41 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6254 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -1.36 | |
| Confidence Interval |
(2-Sided) 95% -2.60 to -0.13 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6279 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -0.87 | |
| Confidence Interval |
(2-Sided) 95% -2.06 to 0.33 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6103 |
|
| Estimation Comments | ||
| Title | Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 2 |
|---|---|
| Description | 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. |
| Time Frame | From Baseline to Week 24 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with HbA1c ≥10.1% and ≤12% at enrollment nonmissing baseline and Week 24 LOCF values. |
| Arm/Group Title | Group 2: Dapagliflozin, 5 mg AM | Group 2: Dapagliflozin, 10 mg AM |
|---|---|---|
| Arm/Group Description | Participants with hemoglobin A1c (HbA1c) ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 34 | 37 |
| Mean (Standard Deviation) [Kilograms] |
-2.06
(3.437)
|
-1.90
(3.539)
|
| Title | Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 1 |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 1 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with nonmissing baseline and Week 24 LOCF values |
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 71 | 57 | 56 | 65 | 48 | 54 | 60 |
| Mean (Standard Error) [mg/dL] |
-2.4
(2.885)
|
-2.9
(3.219)
|
-16.4
(3.248)
|
-16.1
(3.016)
|
-14.4
(3.086)
|
-18.6
(3.219)
|
-20.3
(3.088)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.4 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.324 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -13.9 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.342 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -13.6 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.176 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -12.0 | |
| Confidence Interval |
(2-Sided) 95% -20.3 to -3.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.223 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -16.2 | |
| Confidence Interval |
(2-Sided) 95% -24.7 to -7.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.321 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -17.9 | |
| Confidence Interval |
(2-Sided) 95% -26.2 to -9.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 4.228 |
|
| Estimation Comments | ||
| Title | Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 2 |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with HbA1c ≥10.1% and ≤12% at enrollment with nonmissing baseline and Week 24 LOCF values |
| Arm/Group Title | Group 2: Dapagliflozin, 5 mg AM | Group 2: Dapagliflozin, 10 mg AM |
|---|---|---|
| Arm/Group Description | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 34 | 37 |
| Mean (Standard Deviation) [mg/dL] |
-54.3
(41.9)
|
-74.3
(51.09)
|
| Title | Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1c] <7.0%) at Week 24 (Last Observation Carried Forward [LOCF]) |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 24 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who had nonmissing baseline and Week 24 LOCF values |
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 72 | 64 | 61 | 65 | 62 | 63 | 73 |
| Number [Percentage of participants] |
31.6
42.1%
|
41.3
63.5%
|
44.2
69.1%
|
50.8
72.6%
|
51.4
76.7%
|
44.0
64.7%
|
51.6
67.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage difference |
| Estimated Value | 9.7 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage difference |
| Estimated Value | 12.6 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage difference |
| Estimated Value | 19.2 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percent difference from placebo |
| Estimated Value | 19.8 | |
| Confidence Interval |
(2-Sided) 95% 4.9 to 34.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percent difference from placebo |
| Estimated Value | 12.4 | |
| Confidence Interval |
(2-Sided) 95% -2.5 to 27.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percent difference from placebo |
| Estimated Value | 19.9 | |
| Confidence Interval |
(2-Sided) 95% 5.3 to 34.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) in Patients With Baseline HbA1c ≥9.0% (Last Observation Carried Forward [LOCF]) |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 24 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with nonmissing baseline and Week24 LOCF values. |
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapaglifozon, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with hemoglobin A1c (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks.Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 5 | 8 | 9 | 14 | 11 | 8 | 12 |
| Mean (Standard Error) [Percent] |
0.19
(0.5473)
|
-1.26
(0.4327)
|
-2.00
(0.4079)
|
-2.04
(0.3307)
|
-1.35
(0.3710)
|
-1.53
(0.4416)
|
-1.21
(0.3643)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.45 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6979 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.19 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6828 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.23 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6404 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -1.55 | |
| Confidence Interval |
(2-Sided) 95% -3.33 to -0.42 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7394 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -1.27 | |
| Confidence Interval |
(2-Sided) 95% -2.69 to 0.16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7257 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -0.87 | |
| Confidence Interval |
(2-Sided) 95% -2.06 to 0.33 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6103 |
|
| Estimation Comments | ||
| Title | 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]) |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 24 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with baseline BMI ≥27 kg/m^2 and nonmissing baseline and Week 24 LOCF values |
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 58 | 53 | 53 | 59 | 48 | 54 | 60 |
| Mean (Standard Error) [Percent] |
-0.21
(0.1210)
|
-0.58
(0.1265)
|
-0.73
(0.1267)
|
-0.88
(0.1201)
|
-0.81
(0.1329)
|
-0.76
(0.1255)
|
-0.80
(0.1194)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.37 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1750 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.52 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1750 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.67 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1708 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -0.60 | |
| Confidence Interval |
(2-Sided) 95% -0.95 to -0.25 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1798 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -0.55 | |
| Confidence Interval |
(2-Sided) 95% -0.89 to -0.21 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1741 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -0.58 | |
| Confidence Interval |
(2-Sided) 95% -0.92 to -0.25 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1704 |
|
| Estimation Comments | ||
| Title | Adjusted Percentage of Participants Who Achieved Hemoglobin A1c [HbA1c] ≤6.5% (Last Observation Carried Forward [LOCF]) |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 24 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with HbA1c values at both baseline and Week 24 (LOCF) |
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 11 | 17 | 17 | 14 | 62 | 63 | 73 |
| Number [Percentage of participants] |
14.5
19.3%
|
27.2
41.8%
|
26.6
41.6%
|
23.1
33%
|
33.4
49.9%
|
25.8
37.9%
|
26.0
34.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 12.6 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.526 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 12.1 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.761 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 8.6 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.334 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percent difference from placebo |
| Estimated Value | 18.8 | |
| Confidence Interval |
(2-Sided) 95% 5.5 to 32.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percent difference from placebo |
| Estimated Value | 11.3 | |
| Confidence Interval |
(2-Sided) 95% -1.8 to 24.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percent difference from placebo |
| Estimated Value | 11.4 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 23.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 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) |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 24 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with baseline BMI ≥27 kg/m^2 and nonmissing baseline and Week 24 values |
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 60 | 54 | 54 | 63 | 53 | 57 | 61 |
| Mean (Standard Error) [Kilograms] |
-2.43
(0.5063)
|
-3.43
(0.5341)
|
-2.91
(0.5357)
|
-3.39
(0.4945)
|
-4.30
(0.5388)
|
-3.70
(0.5199)
|
-3.39
(0.5027)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.00 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7360 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.48 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7371 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg AM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.96 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7078 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 2.5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -1.87 | |
| Confidence Interval |
(2-Sided) 95% -3.33 to -0.42 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7394 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 5 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -1.27 | |
| Confidence Interval |
(2-Sided) 95% -2.69 to 0.16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7257 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Dapagliflozin Placebo AM & PM, Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference from placebo |
| Estimated Value | -0.97 | |
| Confidence Interval |
() 95% -2.37 to 0.44 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7135 |
|
| Estimation Comments | ||
| Title | 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) |
|---|---|
| Description | 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. |
| Time Frame | Day 1 to Week 102 (end of Long-term Period) + 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study medication |
| Arm/Group Title | Group 1: Dapagliflozin Placebo, AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM | Group 2: Dapagliflozin, 5 mg AM | Group 2: Dapagliflozin, 10 mg AM |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. In addition, during the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. In addition, during the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. In addition, during the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. In addition, during the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. In addition, during the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. In addition, during the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. In addition, during the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 75 | 65 | 64 | 70 | 67 | 68 | 76 | 34 | 39 |
| >=1 AE |
58
77.3%
|
48
73.8%
|
43
67.2%
|
56
80%
|
50
74.6%
|
50
73.5%
|
54
71.1%
|
29
85.3%
|
33
84.6%
|
| >=1 Hypoglycemia |
4
5.3%
|
3
4.6%
|
0
0%
|
3
4.3%
|
2
3%
|
0
0%
|
2
2.6%
|
1
2.9%
|
1
2.6%
|
| >=1 Related AEs |
15
20%
|
13
20%
|
10
15.6%
|
17
24.3%
|
19
28.4%
|
18
26.5%
|
21
27.6%
|
12
35.3%
|
10
25.6%
|
| Deaths |
0
0%
|
0
0%
|
0
0%
|
1
1.4%
|
1
1.5%
|
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
| SAEs |
5
6.7%
|
6
9.2%
|
4
6.3%
|
1
1.4%
|
7
10.4%
|
5
7.4%
|
3
3.9%
|
1
2.9%
|
0
0%
|
| >=1 related SAE |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| SAEs leading to discontinuation |
1
1.3%
|
0
0%
|
1
1.6%
|
0
0%
|
1
1.5%
|
2
2.9%
|
1
1.3%
|
0
0%
|
0
0%
|
| AE leading to discontinuation |
4
5.3%
|
4
6.2%
|
4
6.3%
|
5
7.1%
|
2
3%
|
6
8.8%
|
7
9.2%
|
0
0%
|
1
2.6%
|
| Hypoglycemia leading to discontinuation |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) (Last Observation Carried Forward [LOCF]): Group 2 |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 24 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants with HbA1c ≥10.1% and ≤12% at enrollment and nonmissing baseline and Week 24 LOCF values |
| Arm/Group Title | Group 2: Dapagliflozin, 5 mg AM | Group 2: Dapagliflozin, 10 mg AM |
|---|---|---|
| Arm/Group Description | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 25 | 32 |
| Mean (Standard Deviation) [Percent] |
-2.88
(1.406)
|
-2.66
(1.261)
|
| Title | Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Laboratory Abnormality (Short-term and Long-term Periods) |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 102 (end of Long-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study medication and with laboratory test results available |
| Arm/Group Title | Group 1: Dapagliflozin Placebo | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM | Group 2: Dapagliflozin, 5 mg AM | Group 2: Dapagliflozin, 10 mg AM |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, PM, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, PM, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, PM, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. | Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal. |
| Measure Participants | 75 | 65 | 62 | 70 | 67 | 66 | 73 | 34 | 39 |
| Hematocrit (>55%) |
0
0%
|
1
1.5%
|
0
0%
|
2
2.9%
|
2
3%
|
1
1.5%
|
4
5.3%
|
2
5.9%
|
4
10.3%
|
| Hematocrit (>60%) |
0
0%
|
0
0%
|
0
0%
|
1
1.4%
|
0
0%
|
0
0%
|
1
1.3%
|
0
0%
|
1
2.6%
|
| Hemoglobin (>18 g/dL) |
0
0%
|
3
4.6%
|
2
3.1%
|
4
5.7%
|
2
3%
|
1
1.5%
|
6
7.9%
|
3
8.8%
|
5
12.8%
|
| Glucose ( >350 mg/dL) |
2
2.7%
|
2
3.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Glucose (<54 mg/dL) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Creatine kinase (>5*ULN) |
1
1.3%
|
0
0%
|
0
0%
|
1
1.4%
|
1
1.5%
|
1
1.5%
|
2
2.6%
|
0
0%
|
0
0%
|
| Creatine kinase (>10*ULN) |
0
0%
|
0
0%
|
0
0%
|
1
1.4%
|
1
1.5%
|
1
1.5%
|
1
1.3%
|
0
0%
|
0
0%
|
| Calcium, total (<7.5 mg/dL) |
3
4%
|
0
0%
|
0
0%
|
0
0%
|
3
4.5%
|
2
2.9%
|
1
1.3%
|
0
0%
|
0
0%
|
| Bicarbonate (<=13 mEq/L) |
0
0%
|
0
0%
|
1
1.6%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Potassium, serum (>=6 mEqL) |
3
4%
|
1
1.5%
|
1
1.6%
|
2
2.9%
|
4
6%
|
1
1.5%
|
1
1.3%
|
1
2.9%
|
1
2.6%
|
| Sodium, serum (<130 mEq/L) |
1
1.3%
|
2
3.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.3%
|
0
0%
|
1
2.6%
|
| Sodium, serum (>150 mEq/L) |
1
1.3%
|
1
1.5%
|
0
0%
|
0
0%
|
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Phosphorus, inorganic (high) |
2
2.7%
|
0
0%
|
1
1.6%
|
0
0%
|
0
0%
|
3
4.4%
|
2
2.6%
|
0
0%
|
2
5.1%
|
| Albumin/creatinine ratio (>1800 mg/g) |
0
0%
|
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Creatinine (>=1.5 preRX creatinine) |
0
0%
|
1
1.5%
|
2
3.1%
|
1
1.4%
|
1
1.5%
|
1
1.5%
|
1
1.3%
|
1
2.9%
|
1
2.6%
|
| Title | Number of Participants With Elevated Levels of Liver Enzymes on Laboratory Test Results (Short-term and Long-term Periods) |
|---|---|
| Description | 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. |
| Time Frame | Day 1 to Week 102 (end of Long-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study medication and with laboratory test results available |
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, PM, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, PM, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. |
| Measure Participants | 75 | 65 | 64 | 70 | 67 | 68 | 76 |
| AST >3*ULN (n=75, 65, 62, 70, 67, 67, 74, 34, 37)) |
0
0%
|
1
1.5%
|
1
1.6%
|
0
0%
|
5
7.5%
|
1
1.5%
|
4
5.3%
|
| AST >5*ULN (n=75, 65, 62, 70, 67, 67, 74) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
3%
|
0
0%
|
0
0%
|
| ALT >3*ULN (n=75, 65, 62, 70, 67, 67, 74) |
1
1.3%
|
1
1.5%
|
2
3.1%
|
1
1.4%
|
0
0%
|
0
0%
|
0
0%
|
| ALT >5*ULN (n=75, 65, 62, 70, 67, 67, 74) |
0
0%
|
1
1.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Bilirubin >1.5 ULN (n=75, 65, 62, 70, 67, 67, 74) |
2
2.7%
|
0
0%
|
1
1.6%
|
0
0%
|
2
3%
|
1
1.5%
|
0
0%
|
| Bilirubin >2*ULN (n=75, 65, 62, 70, 67, 67, 74) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.5%
|
0
0%
|
0
0%
|
| ALP >1.5*ULN (n=75, 65, 62, 70, 67, 67, 74) |
4
5.3%
|
3
4.6%
|
1
1.6%
|
1
1.4%
|
4
6%
|
3
4.4%
|
2
2.6%
|
| Title | Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Findings (Last Observation Carried Forward {LOCF]) |
|---|---|
| Description | 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. |
| Time Frame | Baseline to Week 24 (end of Short-term Period) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study medication and who had measurements available |
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. |
| Measure Participants | 75 | 65 | 64 | 70 | 67 | 68 | 76 |
| Baseline: Normal/Week 24: Normal |
38
50.7%
|
36
55.4%
|
32
50%
|
31
44.3%
|
33
49.3%
|
33
48.5%
|
35
46.1%
|
| Baseline: Normal/Week 24: Abnormal |
6
8%
|
3
4.6%
|
5
7.8%
|
1
1.4%
|
3
4.5%
|
6
8.8%
|
10
13.2%
|
| Baseline: Normal/Week 24: Not reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Baseline: Abnormal/Week 24: Normal |
5
6.7%
|
2
3.1%
|
3
4.7%
|
6
8.6%
|
4
6%
|
4
5.9%
|
10
13.2%
|
| Baseline: Abnormal/Week 24: Abnormal |
18
24%
|
17
26.2%
|
11
17.2%
|
17
24.3%
|
17
25.4%
|
14
20.6%
|
11
14.5%
|
| Baseline: Abnormal/Week 24: Not reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Baseline: Not reported/Week 24: Normal |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Basline: Not reported/Week 24: Abnormal |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Baseline: Not reported/Week 24: Not reported |
8
10.7%
|
7
10.8%
|
13
20.3%
|
15
21.4%
|
10
14.9%
|
11
16.2%
|
10
13.2%
|
Adverse Events
| Time Frame | Day 1 to Week 102 (end of Long-term Period) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||||||||||||
| Arm/Group Title | Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM | |||||||
| Arm/Group Description | Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. | |||||||
All Cause Mortality |
||||||||||||||
| Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||||
Serious Adverse Events |
||||||||||||||
| Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/75 (6.7%) | 6/65 (9.2%) | 4/64 (6.3%) | 1/70 (1.4%) | 7/67 (10.4%) | 5/68 (7.4%) | 3/76 (3.9%) | |||||||
| Cardiac disorders | ||||||||||||||
| Cardiac failure | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 1/67 (1.5%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Acute myocardial infarction | 0/75 (0%) | 0/65 (0%) | 1/64 (1.6%) | 0/70 (0%) | 1/67 (1.5%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Acute coronary syndrome | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 1/68 (1.5%) | 0/76 (0%) | |||||||
| Angina pectoris | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 2/68 (2.9%) | 0/76 (0%) | |||||||
| Atrial fibrillation | 1/75 (1.3%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Mitral valve incompetence | 1/75 (1.3%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Ear and labyrinth disorders | ||||||||||||||
| Vertigo | 1/75 (1.3%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Abdominal hernia | 0/75 (0%) | 1/65 (1.5%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Abdominal pain lower | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 1/76 (1.3%) | |||||||
| General disorders | ||||||||||||||
| Adverse drug reaction | 1/75 (1.3%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Chest pain | 1/75 (1.3%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Pneumonia | 1/75 (1.3%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 2/67 (3%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Influenza | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 2/67 (3%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Infective exacerbation of chronic obstructive airways disease | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 1/76 (1.3%) | |||||||
| Pilonidal cyst | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 1/67 (1.5%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Arthritis bacterial | 0/75 (0%) | 1/65 (1.5%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Staphylococcal infection | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 1/76 (1.3%) | |||||||
| Staphylococcal bacteraemia | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 1/76 (1.3%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Contusion | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 1/70 (1.4%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Investigations | ||||||||||||||
| Albumin urine present | 0/75 (0%) | 1/65 (1.5%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Urine albumin/creatinine ratio increased | 0/75 (0%) | 1/65 (1.5%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| Malignant melanoma | 1/75 (1.3%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 1/68 (1.5%) | 0/76 (0%) | |||||||
| Gastric cancer | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 1/68 (1.5%) | 0/76 (0%) | |||||||
| Breast cancer | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 1/67 (1.5%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Colon neoplasm | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 1/76 (1.3%) | |||||||
| Metastases to central nervous system | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 1/68 (1.5%) | 0/76 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Cerebrovascular accident | 0/75 (0%) | 1/65 (1.5%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Diabetic hyperosmolar coma | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 1/67 (1.5%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Pregnancy, puerperium and perinatal conditions | ||||||||||||||
| Abortion spontaneous | 0/75 (0%) | 0/65 (0%) | 1/64 (1.6%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Renal and urinary disorders | ||||||||||||||
| Renal failure acute | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 1/67 (1.5%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Glomerulonephritis acute | 0/75 (0%) | 0/65 (0%) | 1/64 (1.6%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Malacoplakia vesicae | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 1/67 (1.5%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Reproductive system and breast disorders | ||||||||||||||
| Benign prostatic hyperplasia | 0/75 (0%) | 1/65 (1.5%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Pulmonary arterial hypertension | 1/75 (1.3%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Pulmonary embolism | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 1/68 (1.5%) | 0/76 (0%) | |||||||
| Pulmonary mass | 0/75 (0%) | 0/65 (0%) | 1/64 (1.6%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Epistaxis | 1/75 (1.3%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Haemothorax | 0/75 (0%) | 1/65 (1.5%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Angioedema | 0/75 (0%) | 0/65 (0%) | 1/64 (1.6%) | 0/70 (0%) | 1/67 (1.5%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Vascular disorders | ||||||||||||||
| Femoral artery occlusion | 0/75 (0%) | 1/65 (1.5%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 0/68 (0%) | 0/76 (0%) | |||||||
| Venous thrombosis | 0/75 (0%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 0/67 (0%) | 1/68 (1.5%) | 0/76 (0%) | |||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||
| Group 1: Dapagliflozin Placebo AM & PM | Group 1: Dapagliflozin, 2.5 mg AM | Group 1: Dapagliflozin, 5 mg AM | Group 1: Dapagliflozin, 10 mg AM | Group 1: Dapagliflozin, 2.5 mg PM | Group 1: Dapagliflozin, 5 mg PM | Group 1: Dapagliflozin, 10 mg PM | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 40/75 (53.3%) | 40/65 (61.5%) | 33/64 (51.6%) | 41/70 (58.6%) | 38/67 (56.7%) | 39/68 (57.4%) | 39/76 (51.3%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Constipation | 1/75 (1.3%) | 2/65 (3.1%) | 1/64 (1.6%) | 1/70 (1.4%) | 4/67 (6%) | 2/68 (2.9%) | 2/76 (2.6%) | |||||||
| Diarrhoea | 5/75 (6.7%) | 6/65 (9.2%) | 2/64 (3.1%) | 4/70 (5.7%) | 4/67 (6%) | 7/68 (10.3%) | 6/76 (7.9%) | |||||||
| Abdominal pain | 2/75 (2.7%) | 0/65 (0%) | 0/64 (0%) | 0/70 (0%) | 6/67 (9%) | 4/68 (5.9%) | 2/76 (2.6%) | |||||||
| Nausea | 1/75 (1.3%) | 3/65 (4.6%) | 3/64 (4.7%) | 1/70 (1.4%) | 1/67 (1.5%) | 3/68 (4.4%) | 4/76 (5.3%) | |||||||
| Toothache | 0/75 (0%) | 4/65 (6.2%) | 0/64 (0%) | 1/70 (1.4%) | 4/67 (6%) | 1/68 (1.5%) | 1/76 (1.3%) | |||||||
| Gastritis | 3/75 (4%) | 1/65 (1.5%) | 0/64 (0%) | 1/70 (1.4%) | 2/67 (3%) | 3/68 (4.4%) | 4/76 (5.3%) | |||||||
| General disorders | ||||||||||||||
| Oedema peripheral | 2/75 (2.7%) | 1/65 (1.5%) | 2/64 (3.1%) | 1/70 (1.4%) | 2/67 (3%) | 3/68 (4.4%) | 6/76 (7.9%) | |||||||
| Infections and infestations | ||||||||||||||
| Bronchitis | 5/75 (6.7%) | 2/65 (3.1%) | 1/64 (1.6%) | 4/70 (5.7%) | 5/67 (7.5%) | 4/68 (5.9%) | 4/76 (5.3%) | |||||||
| Influenza | 3/75 (4%) | 7/65 (10.8%) | 5/64 (7.8%) | 5/70 (7.1%) | 1/67 (1.5%) | 6/68 (8.8%) | 5/76 (6.6%) | |||||||
| Pharyngitis | 6/75 (8%) | 1/65 (1.5%) | 6/64 (9.4%) | 5/70 (7.1%) | 6/67 (9%) | 1/68 (1.5%) | 4/76 (5.3%) | |||||||
| Upper respiratory tract infection | 4/75 (5.3%) | 4/65 (6.2%) | 1/64 (1.6%) | 5/70 (7.1%) | 3/67 (4.5%) | 2/68 (2.9%) | 9/76 (11.8%) | |||||||
| Urinary tract infection | 3/75 (4%) | 3/65 (4.6%) | 5/64 (7.8%) | 5/70 (7.1%) | 4/67 (6%) | 7/68 (10.3%) | 5/76 (6.6%) | |||||||
| Vulvovaginal mycotic infection | 0/75 (0%) | 1/65 (1.5%) | 0/64 (0%) | 4/70 (5.7%) | 2/67 (3%) | 1/68 (1.5%) | 1/76 (1.3%) | |||||||
| Gastroenteritis | 3/75 (4%) | 2/65 (3.1%) | 1/64 (1.6%) | 2/70 (2.9%) | 1/67 (1.5%) | 5/68 (7.4%) | 2/76 (2.6%) | |||||||
| Nasopharyngitis | 7/75 (9.3%) | 11/65 (16.9%) | 5/64 (7.8%) | 10/70 (14.3%) | 11/67 (16.4%) | 9/68 (13.2%) | 7/76 (9.2%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Back pain | 5/75 (6.7%) | 3/65 (4.6%) | 4/64 (6.3%) | 5/70 (7.1%) | 2/67 (3%) | 6/68 (8.8%) | 7/76 (9.2%) | |||||||
| Pain in extremity | 4/75 (5.3%) | 4/65 (6.2%) | 3/64 (4.7%) | 3/70 (4.3%) | 2/67 (3%) | 1/68 (1.5%) | 4/76 (5.3%) | |||||||
| Arthralgia | 3/75 (4%) | 6/65 (9.2%) | 5/64 (7.8%) | 6/70 (8.6%) | 3/67 (4.5%) | 8/68 (11.8%) | 6/76 (7.9%) | |||||||
| Myalgia | 2/75 (2.7%) | 2/65 (3.1%) | 2/64 (3.1%) | 2/70 (2.9%) | 4/67 (6%) | 3/68 (4.4%) | 0/76 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Dizziness | 2/75 (2.7%) | 3/65 (4.6%) | 1/64 (1.6%) | 2/70 (2.9%) | 6/67 (9%) | 4/68 (5.9%) | 3/76 (3.9%) | |||||||
| Headache | 9/75 (12%) | 6/65 (9.2%) | 5/64 (7.8%) | 6/70 (8.6%) | 4/67 (6%) | 11/68 (16.2%) | 10/76 (13.2%) | |||||||
| Psychiatric disorders | ||||||||||||||
| Insomnia | 2/75 (2.7%) | 1/65 (1.5%) | 0/64 (0%) | 1/70 (1.4%) | 0/67 (0%) | 0/68 (0%) | 4/76 (5.3%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Cough | 4/75 (5.3%) | 4/65 (6.2%) | 3/64 (4.7%) | 3/70 (4.3%) | 3/67 (4.5%) | 3/68 (4.4%) | 3/76 (3.9%) | |||||||
| Vascular disorders | ||||||||||||||
| Hypertension | 3/75 (4%) | 4/65 (6.2%) | 4/64 (6.3%) | 3/70 (4.3%) | 5/67 (7.5%) | 3/68 (4.4%) | 4/76 (5.3%) | |||||||
Limitations/Caveats
Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was an exploratory group, included to obtain initial efficacy and safety data. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
| Name/Title | Boaz Hirshberg |
|---|---|
| Organization | AstraZeneca Pharmaceuticals |
| Phone | |
| ClinicalTrialTransparency@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00528372
Other Study ID Numbers:
- MB102-013 LT
First Posted:
Sep 12, 2007
Last Update Posted:
Oct 20, 2015
Last Verified:
Sep 1, 2015