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

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Combination With Metformin in Asian Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone

The purpose of this clinical research study is to learn if BMS-512148 (Dapagliflozin) can help reduce the blood sugar levels in Asian patients with Type 2 Diabetes who are not well controlled on metformin alone. The safety of this treatment will also be studied.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Dapagliflozin; Drug: Metformin; Drug: Dapagliflozin Placebo; Drug: Pioglitazone

• Study Type: Interventional
• Enrollment (Actual): 1484
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Xi'An, China, 710032
    • Local Institution
  • Anhui
    • Hefei, Anhui, China, 230022
      • Local Institution
  • Beijing
    • Beijing, Beijing, China, 100730
      • Local Institution
    • Beijing, Beijing, China, 100001
      • Local Institution
    • Beijing, Beijing, China, 100044
      • Local Institution
    • Beijing, Beijing, China, 100029
      • Local Institution
    • Beijing, Beijing, China, 100700
      • Local Institution
  • Chongqing
    • Chongqing, Chongqing, China, 400016
      • Local Institution
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Local Institution
  • Heilongjiang
    • Haerbin, Heilongjiang, China, 150001
      • Local Institution
  • Hunan
    • Changsha, Hunan, China, 410008
      • Local Institution
    • Changsha, Hunan, China, 410000
      • Local Institution
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Local Institution
    • Nanjing, Jiangsu, China, 210006
      • Local Institution
    • Wuxi, Jiangsu, China, 214023
      • Local Institution
  • Jilin
    • Changchun, Jilin, China, 130041
      • Local Institution
  • Liaoning
    • Shenyang, Liaoning, China, 110003
      • Local Institution
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Local Institution
    • Shanghai, Shanghai, China, 200003
      • Local Institution
    • Shanghai, Shanghai, China, 200065
      • Local Institution
  • Sichuan
    • Chengdu, Sichuan, China, 610070
      • Local Institution
    • Chongqing, Sichuan, China, 400010
      • Local Institution
  • Tianjin
    • Tianjin, Tianjin, China, 300211
      • Local Institution
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Local Institution
• India
  • Bangalore, India, 560092
    • Local Institution
  • Jaipur, India, 302023
    • Local Institution
  • Vellore, Tamilnadu, India, 632004
    • Local Institution
  • Karnataka
    • Bangalore, Karnataka, India, 560 043
      • Local Institution
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India, 452010
      • Local Institution
• Korea, Republic of
  • Busan, Korea, Republic of, 614-735
    • Local Institution
  • Seoul, Korea, Republic of, 120-752
    • Local Institution
  • Seoul, Korea, Republic of, 137-040
    • Local Institution
  • Nowon-Gu
    • Seoul, Nowon-Gu, Korea, Republic of, 139-711
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females, 18 to 77 years old, with type 2 diabetes and with inadequate glycemic control
• Drug naive or treated with anti-diabetic medication for < 24 weeks
• C-peptide ≥ 1.0 ng/mL
• Body Mass Index ≤ 45.0 kg/m²

Exclusion Criteria:

• AST and/or ALT > 3 times ULN
• Serum total bilirubin > 2 mg/dL
• Serum creatinine ≥ 1.50 mg/dL for men or ≥ 1.40 mg/dL for women
• Creatine kinase ≥ 3 times ULN
• Symptoms of severely uncontrolled diabetes
• Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 2	Drug: Dapagliflozin; Tablets, Oral, 5 mg, Once daily, 24 weeks; Other Names: BMS-512148; Drug: Dapagliflozin; Tablets, Oral, 10 mg, Once daily, 24 weeks; Other Names: BMS-512148; Drug: Metformin; Tablets, Oral, 1500-3000 mg, Twice daily, 24 weeks; Other Names: Glucophage®; Drug: Dapagliflozin Placebo; Tablets, Oral, 0 mg, Once daily, 24 weeks; Drug: Pioglitazone; Tablets, Oral, 15-45 mg (as needed for rescue based on protocol specific criteria), Up to 20 weeks
Experimental: Group 1	Drug: Dapagliflozin; Tablets, Oral, 5 mg, Once daily, 24 weeks; Other Names: BMS-512148; Drug: Dapagliflozin; Tablets, Oral, 10 mg, Once daily, 24 weeks; Other Names: BMS-512148; Drug: Metformin; Tablets, Oral, 1500-3000 mg, Twice daily, 24 weeks; Other Names: Glucophage®; Drug: Dapagliflozin Placebo; Tablets, Oral, 0 mg, Once daily, 24 weeks; Drug: Pioglitazone; Tablets, Oral, 15-45 mg (as needed for rescue based on protocol specific criteria), Up to 20 weeks
Experimental: Group 3	Drug: Metformin; Tablets, Oral, 1500-3000 mg, Twice daily, 24 weeks; Other Names: Glucophage®; Drug: Dapagliflozin Placebo; Tablets, Oral, 0 mg, Once daily, 24 weeks; Drug: Pioglitazone; Tablets, Oral, 15-45 mg (as needed for rescue based on protocol specific criteria), Up to 20 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF])	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.	From Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 of the double-blind period.	From Baseline to Week 24
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 in the double-blind period.	From Baseline to Week 24
Adjusted Mean Change From Baseline in 2-hour Post Meal Glucose (PMG) (mg/dL) at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Post Meal Glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. PMG measurements were obtained on Day 1 and week 24 in the double-blind period.	From Baseline to Week 24
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using 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. HbA1c was measured as a percent of hemoglobin. Percentage of participants were estimated by modified logistic regression model, adjusted for baseline HbA1c.	From Baseline to Week 24

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: AstraZeneca, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• Publication

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: March 26, 2010
• First Submitted That Met QC Criteria: March 26, 2010
• First Posted (Estimate): March 30, 2010

Study Record Updates

• Last Update Posted (Actual): September 11, 2017
• Last Update Submitted That Met QC Criteria: September 4, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Metformin; Pioglitazone
• Other Study ID Numbers: MB102-055