Effects of Dapagliflozin on Kidney Function (Glomerular Filtration Rate) in Subjects With Type 2 Diabetes

An Exploratory Phase 2 Study to Assess the Effect of Dapagliflozin on Glomerular Filtration Rate (GFR) in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic and Blood Pressure (BP) Control

The purpose of this study is to evaluate the effects of dapagliflozin on kidney function, as assessed by glomerular filtration rate.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: Dapagliflozin; Drug: Hydrochlorothiazide

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 3E8
      • Local Institution
  • Quebec
    • Laval, Quebec, Canada, H7T 2P5
      • Local Institution
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Local Institution
• United States
  • California
    • Anaheim, California, United States, 92801
      • Advanced Clinical Res Inst
    • Lomita, California, United States, 90717
      • Torrance Clinical Research
  • Florida
    • Miami, Florida, United States, 33169
      • Elite Research Institute
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • University of Michigan
  • Minnesota
    • St. Paul, Minnesota, United States, 55114
      • Prism Research
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Memorial Hospital of Rhode Island
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53295
      • Zablocki Veterans Affairs Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetes and inadequate glycemic control, defined as A1C ≥ 6.6 and ≤ 9.5%
• Stable dose of metformin AND/OR a sulfonylurea, for at least 4 weeks prior to the enrollment visit
• Inadequate blood pressure (BP) control, defined as systolic BP (SBP) ≥ 130 and < 165 mmHg, AND/OR diastolic BP (DBP) ≥ 80 and < 105 mmHg
• C-peptide ≥ 0.8 ng/mL
• Estimated GFR by the Modification of Diet in Renal Disease (MDRD) formula > 60 mL/min/1.73m² and < 150 mL/min/1.73m²
• Urine albumin:creatinine ratio (UACR) < 300 mg/g
• BMI ≤ 45.0 kg/m2

Exclusion Criteria:

• Administration of diuretics or other medication approved for the treatment of hypertension (with the exception of either ACEI or ARB), at any dose during the 12 weeks prior to the enrollment visit
• History of adverse reaction to radio-contrast dye
• Allergy or contraindication to use of thiazide diuretics
• Aspartate Aminotransferase (AST) > 3X Upper limit of normal (ULN)
• Alanine aminotransferase (ALT) > 3X ULN
• Serum Total Bilirubin > 1.5X ULN
• Serum Creatinine (Scr) ≥ 1.50 mg/dL (133 μmol/l) for men; SCr ≥ 1.40 mg/dL (124 μmol/l) for women
• Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncologic, endocrine, psychiatric, or rheumatic diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin	Drug: Placebo; Tablets, Oral, 0 mg, once daily, 12 weeks; Drug: Dapagliflozin; Tablets, Oral, 10 mg, once daily, 12 weeks; Other Names: BMS-512148
Active Comparator: Hydrochlorothiazide	Drug: Hydrochlorothiazide; Tablets, Oral, 25 mg, once daily, 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Percent Change From Baseline in Glomerular Filtration Rate (GFR) at Week 12 (Modified Last Observation Carried Forward [MLOCF])	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 12 measurement was available, the last available post-baseline measurement obtained on or after Day 23 was used regardless of rescue medication. Measurements were obtained during radomization visit, and Week 12 in the double-blind period by a central laboratory.	From Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline in 24-Hour Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF])	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. Measurements were obtained during lead-in, and Week 12 in the double-blind period.	From Baseline to Week 12
Adjusted Mean Change From Baseline in Daytime (0900 to 2100 Hours) Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF])	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. Measurements were obtained during lead-in, and Week 12 in the double-blind period.	From Baseline to Week 12
Adjusted Mean Change From Baseline in Nighttime (0100 to 0600 Hours) Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF])	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. Measurements were obtained during lead-in, and Week 12 in the double-blind period.	From Baseline to Week 12

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Publication
• MB102035_Redacted_CSR_synopsis

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: September 11, 2009
• First Submitted That Met QC Criteria: September 11, 2009
• First Posted (Estimate): September 14, 2009

Study Record Updates

• Last Update Posted (Actual): March 8, 2017
• Last Update Submitted That Met QC Criteria: January 18, 2017
• Last Verified: January 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; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium-Glucose Transporter 2 Inhibitors; Sodium Chloride Symporter Inhibitors; Dapagliflozin; Hydrochlorothiazide
• Other Study ID Numbers: MB102-035; EUDRACT #: 2009-010221-39