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

Back to results

Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Dapagliflozin

Placebo

Hydrochlorothiazide

About this trial

This is an interventional basic science trial for Type 2 Diabetes Mellitus

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Dapagliflozin

Hydrochlorothiazide

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT00976495

First Posted

September 11, 2009

Last Updated

January 18, 2017

Sponsor

AstraZeneca

Collaborators

Astra Zeneca, Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT00976495

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Completed

Study Start Date

October 2009 (undefined)

Primary Completion Date

November 2010 (Actual)

Study Completion Date

November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

Collaborators

Astra Zeneca, Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

154 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dapagliflozin

Arm Type

Experimental

Arm Title

Hydrochlorothiazide

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin

Other Intervention Name(s)

BMS-512148

Intervention Description

Tablets, Oral, 10 mg, once daily, 12 weeks

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Tablets, Oral, 0 mg, once daily, 12 weeks

Intervention Type

Drug

Intervention Name(s)

Hydrochlorothiazide

Intervention Description

Tablets, Oral, 25 mg, once daily, 12 weeks

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

From Baseline to Week 12

Secondary Outcome Measure Information:

Title

Adjusted Mean Change From Baseline in 24-Hour Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF])

Description

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.

Time Frame

From Baseline to Week 12

Title

Adjusted Mean Change From Baseline in Daytime (0900 to 2100 Hours) Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF])

Description

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.

Time Frame

From Baseline to Week 12

Title

Adjusted Mean Change From Baseline in Nighttime (0100 to 0600 Hours) Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF])

Description

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.

Time Frame

From Baseline to Week 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

Facility Information:

Facility Name

Advanced Clinical Res Inst

City

Anaheim

State/Province

California

ZIP/Postal Code

92801

Country

United States

Facility Name

Torrance Clinical Research

City

Lomita

State/Province

California

ZIP/Postal Code

90717

Country

United States

Facility Name

Elite Research Institute

City

Miami

State/Province

Florida

ZIP/Postal Code

33169

Country

United States

Facility Name

Compass Research, Llc

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

Orlando Clinical Research Center

City

Orlando

State/Province

Florida

ZIP/Postal Code

32809

Country

United States

Facility Name

University Of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48106

Country

United States

Facility Name

Prism Research

City

St. Paul

State/Province

Minnesota

ZIP/Postal Code

55114

Country

United States

Facility Name

Memorial Hospital Of Rhode Island

City

Pawtucket

State/Province

Rhode Island

ZIP/Postal Code

02860

Country

United States

Facility Name

Zablocki Veterans Affairs Medical Center

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53295

Country

United States

Facility Name

Local Institution

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M4G 3E8

Country

Canada

Facility Name

Local Institution

City

Laval

State/Province

Quebec

ZIP/Postal Code

H7T 2P5

Country

Canada

Facility Name

Local Institution

City

Groningen

ZIP/Postal Code

9713 GZ

Country

Netherlands

12. IPD Sharing Statement

Links:

URL

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906841/

Description

Publication

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3641&filename=MB102035_Redacted_CSR_synopsis.pdf

Description

MB102035_Redacted_CSR_synopsis

Type 2 Diabetes Mellitus

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial