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

Phase 2

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Hydrochlorothiazide; Drug: Dapagliflozin; Drug: Placebo

• Registration Number: NCT00976495
• Lead Sponsor: AstraZeneca

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-09-11
• Study First Submitted QC: 2009-09-11
• Study First Posted: 2009-09-14
• Study Start: 2009-10
• Primary Completion: 2010-11
• Study Completion: 2010-11
• Disposition First Submitted: 2012-03-24
• Disposition First Submitted QC: 2014-06-06
• Disposition First Posted: 2014-06-18
• Results First Submitted: 2016-09-30
• Status Verified: 2017-01
• Results First Submitted QC: 2017-01-18
• Last Update Submitted: 2017-01-18
• Results First Posted: 2017-03-08
• Last Update Posted: 2017-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 154

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dapagliflozin	Placebo	-
Hydrochlorothiazide	Hydrochlorothiazide	-
Dapagliflozin	Dapagliflozin	-

Primary Outcome Measures

Name	Time	Method
Adjusted Percent Change From Baseline in Glomerular Filtration Rate (GFR) at Week 12 (Modified Last Observation Carried Forward [MLOCF])	From Baseline to Week 12	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.

Secondary Outcome Measures

Name	Time	Method
Adjusted Mean Change From Baseline in Daytime (0900 to 2100 Hours) Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF])	From Baseline to Week 12	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.
Adjusted Mean Change From Baseline in Nighttime (0100 to 0600 Hours) Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF])	From Baseline to Week 12	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.
Adjusted Mean Change From Baseline in 24-Hour Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF])	From Baseline to Week 12	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.

Trial Locations

Locations (10)

Prism Research; 🇺🇸 St. Paul, Minnesota, United States

Memorial Hospital Of Rhode Island; 🇺🇸 Pawtucket, Rhode Island, United States

Local Institution; 🇳🇱 Groningen, Netherlands

Torrance Clinical Research; 🇺🇸 Lomita, California, United States

Advanced Clinical Res Inst; 🇺🇸 Anaheim, California, United States

Elite Research Institute; 🇺🇸 Miami, Florida, United States

Compass Research, Llc; 🇺🇸 Orlando, Florida, United States

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States

University Of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Zablocki Veterans Affairs Medical Center; 🇺🇸 Milwaukee, Wisconsin, United States