A Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin 10 mg in Combination With Metformin as Initial Therapy as Compared With Dapagliflozin 10 mg Monotherapy and Metformin Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control
Overview
- Phase
- Phase 3
- Intervention
- Dapagliflozin
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- AstraZeneca
- Enrollment
- 1093
- Locations
- 64
- Primary Endpoint
- Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 (Last Observation Carried Forward) - Randomized Treated Participants
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The primary purpose of this study is to compare the change from baseline in hemoglobin A1C achieved with dapagliflozin 10 mg in combination with metformin XR as compared with metformin XR monotherapy and compared with Dapagliflozin monotherapy, after 24 weeks of oral administration of double-blind treatment. The safety of treatment with dapagliflozin will also be assessed in this study
Investigators
Eligibility Criteria
Inclusion Criteria
- •Treatment naive males and females, \>= 18 years old and
- •\<= 77 years old, with type 2 diabetes mellitus
- •Subjects must have central laboratory pre-randomization hemoglobin A1C \>= 7.5 and \<= 12.0%
- •C-peptide \>= 1.0 ng/mL (0.34 nmol/L)
- •Body Mass Index \<= 45 kg/m2
- •Must be able to perform self monitoring of blood glucose
Exclusion Criteria
- •aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>3X\*upper limit of normal (ULN)
- •Serum Total bilirubin \>2 mg/dL (34.2 µmol/L)
- •Creatinine kinase \>3\*ULN
- •Serum creatinine \>= 1.50 mg/dL (133 µmol/L) for male subjects, \>= 1.40 mg/dL (124 µmol/L) for female subjects
- •Calcium value outside of the central laboratory normal reference range
- •Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases
- •Urine albumin:creatinine ratio (UACR) \>1800 mg/g (203.4 mg/mmol Cr)
- •Severe uncontrolled hypertension defined as systolic blood pressure (SBP) \>=180 mmHg and/or diastolic blood pressure (DBP) \>=110 mmHg
- •Hemoglobin \>=11.0 g/dL (110 g/L) for men; hemoglobin \>=10.0 g/dL (100 g/L) for women
- •Positive for hepatitis B surface antigen
Arms & Interventions
Dapagliflozin + Metformin XR
Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Intervention: Dapagliflozin
Dapagliflozin + Metformin XR
Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks Metformin XR: Tablets, Oral, up to 2000 mg, once daily, 24 weeks
Intervention: Metformin XR
Dapagliflozin + Placebo
Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks. Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.
Intervention: Dapagliflozin
Dapagliflozin + Placebo
Dapagliflozin: Tablets, Oral, 10 mg, once daily, 24 weeks. Placebo: Metformin HCl Modified Release matching placebo tablets, once daily, 24 weeks.
Intervention: metformin HCl Modified Release matching Placebo
Metformin XR + Placebo
Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks
Intervention: Metformin XR
Metformin XR + Placebo
Metformin XR: Tablets, Oral, 500 mg up to 2000 mg, once daily 24 weeks Placebo: Dapagliflozin matching placebo tablets once daily, 24 weeks
Intervention: dapagliflozin matching Placebo
Outcomes
Primary Outcomes
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24 (Last Observation Carried Forward) - Randomized Treated Participants
Time Frame: Week 24
Adjusted mean change in HbA1c from baseline at Week 24 (or the last post-baseline measurement prior to Week 24 if no Week 24 assessment was available, ie, last observation carried forward (LOCF) was determined. HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the Qualification and Lead-In Periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the Double-Blind Period.
Secondary Outcomes
- Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (LOCF) - Randomized, Treated Participants(Week 24)
- Percent Adjusted for Baseline HbA1c of Participants Achieving a Therapeutic Glycemic Response at Week 24 (LOCF) - Randomized, Treated Participants(Week 24)
- Adjusted Mean Change From Baseline in HbA1C at Week 24 (LOCF) in Participants Whose Baseline HbA1C Category ≥9.0%(Week 24)
- The Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (LOCF) - Randomized, Treated Participants(Week 24)
- Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Discontinuation Due to AEs, During the 12 Week Double Blind Period, Including Data After Rescue - All Treated Participants(Day 1 of Double Blind Period to end of Week 24 Plus 30 days)
- Number of Participants With Adverse Events of Special Interest During the 12 Week Double Blind Period - All Treated Participants(Baseline to last dose plus 4 days in 12 Week Double Blind Period)
- Mean Change From Baseline in Seated Systolic and Diastolic Blood Pressure at Week 24 - Treated Participants(Week 24)
- Mean Change From Baseline in Seated Heart Rate at Week 24 - Randomized, Treated Participants(Week 24)
- Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 24 (LOCF) - Randomized, Treated Participants(Week 24)
- Number of Participants With Marked Laboratory Abnormalities (Not Including Liver Function) in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants(Baseline to Week 24/end of treatment plus 4 days)
- Number of Participants With Marked Laboratory Abnormalities in Liver Function in 24 Week Double Blind Treatment Period, Including Data After Rescue - Randomized, Treated Participants(Baseline to Week 24/end of treatment plus 30 days)