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Study to Evaluate the Effects of BMS-813160 on Protein Loss in the Urine of Subjects With Type 2 Diabetes and Diabetic Kidney Disease

Primary Purpose

Diabetic Kidney Disease

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BMS-813160
Placebo matching with BMS-813160
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Kidney Disease

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Clinical diagnosis of type 2 diabetes mellitus with macroalbuminuria (UACR between 200 and 3500 mg/g)
  • Background angiotensin converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) therapy

Exclusion Criteria:

  • Clinical diagnosis of type 1 diabetes
  • Unstable cardiovascular, metabolic, or other chronic disease status
  • Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2
  • High risk of infection or immune compromise
  • Clinically significant ECG conduction abnormalities
  • Drugs with significant potential to affect BMS-813160 exposure

Sites / Locations

  • Uab Hospital
  • Univ Of Al At Birmingham
  • Akdhc Medical Research Services Llc
  • Academic Medical Research Institute
  • Ucla
  • Providence Clinical Research
  • Diabetes Medical Center Of California
  • Diablo Clinical Research, Inc.
  • George Washington University Medical Faculty Associates
  • All Medical Research, Llc
  • International Research Associates, Llc
  • Genesis Clinical Research, Inc.
  • Emory University School Of Medicine
  • Endocrine Research Solutions, Inc.
  • John H. Stroger, Jr. Hospital Of Cook County
  • Research By Design, Llc
  • St Louis Center Clinl Res
  • St. Louis Center For Clinical Research
  • Va Nebraska-Western Iowa Health Care System (Nwihcs)
  • Southern Nh Diab And Endo
  • Premier Research, Inc.
  • Albany Medical College
  • The Endocrine Group Llp
  • Nephrology Associates
  • Medispect Medical Research, Llc
  • Metrolina Internal Medicine
  • Duke University
  • Ohio State University Medical Center
  • The Ohio State University Wexner Medical Center
  • Paramount Medical Research & Consulting, Llc
  • Physician Research, Inc.
  • Thomas Jefferson University
  • Piedmont Health Grp, Llc-Twr Pt Res Ctr
  • Vanderbilt University Medical Center
  • Vanderbilt University Medical Center
  • Doctors Hospital At Renaissance
  • San Antonio Military Medical Center
  • San Antonio Military Medical Center
  • Northeast Clinical Research Of San Antonio, Llc
  • Burke Internal Medicine And Research
  • Virginia Endocrinology Research
  • Manassas Clinical Research Center
  • Mcguire Va Medical Center
  • Health Sciences Centre Diabetes Research Centre
  • Eastern Health Sciences Center
  • Aggarwal And Associates
  • Clinical Research Solutions, Inc
  • Lmc Diabetes & Endocrinology (Thornhill)
  • Lmc Diabetes & Endocrinology (Bayview)
  • Centre De Recherche Clinique De Laval
  • Recherche Gcp Research
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Arm A: BMS-813160 150 mg & Placebo matching with BMS-813160

Arm B: BMS-813160 300 mg

Arm C: Placebo matching with BMS-813160

Arm Description

BMS-813160 150 mg capsules by mouth in AM and Placebo matching with BMS-813160 in PM for 12 weeks

BMS-813160 300 mg capsules by mouth twice daily for 12 weeks

Placebo matching with BMS-813160 0 mg capsules by mouth twice daily for 12 weeks

Outcomes

Primary Outcome Measures

Percent Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) Across 12 Weeks of Treatment With BMS-813160
The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples. UACR was calculated as the geometric mean of two first-morning void urine UACR measurements with samples collected on two separate occasions within a 4-day period.

Secondary Outcome Measures

Number of Participants With Serious Adverse Events (SAEs), Who Died and With Other (Not Including Serious) Adverse Events
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, or a congenital anomaly, or a medically important event.
Number of Participants With Out-of-Range Electrocardiogram (ECG) Interval
12-lead ECGs were performed before and 1 hour after dosing at Weeks 0, 2 and 4. ECGs were recorded after the participant has been supine for at least 5 minutes. The PR interval was defined as the beginning of the P wave to the beginning of the QRS complex, and represents the time taken by electrical impulse to travel from the sinus node through the atrioventricular (AV) node. The QRS complex represented the rapid depolarization of the right and left ventricles. The QT interval was defined as the time from the start of the Q wave to the end of the T wave, and represents the time taken for ventricular depolarization and repolarization. Participants were evaluated for abnormal ECG intervals. Criteria's for abnormality were PR >200, QRS >120, QT >500, QTcF >450, Change From Baseline >30 milliseconds (msec).
Trough Observed Plasma Concentration (Ctrough) of BMS-813160
Ctrough is the minimum estimated plasma concentration at steady state.
Area Under The Plasma Concentration-Time Curve From Time Zero to 6 Hours Post-Dose [AUC(0-6 h)]
AUC(0-6 h) is the area under the plasma concentration-time curve from pre-dose (0 h) to 6 h post-dose.
Renal Clearance (CLr) of BMS-813160
CLr was calculated by dividing the total amount excreted in the urine from 0 to 6 hours by the area under the plasma concentration-time curve from time zero extrapolated to infinite time. The renal function was classified based on estimated glomerular filtration rate as normal (>=90 mL/min/1.73 m^2), mildly impaired (60-89 mL/min/1.73 m^2), moderately impaired stage 3A (45-59 mL/min/1.73 m^2), and moderately impaired stage 3B (30-44 L/min/1.73 m^2).
Dose-Response Relationship Using Change in Baseline Urinary Albumin-to-Creatinine Ratio (UACR) Across 12 Weeks of Treatment
The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples. UACR was calculated as the geometric mean of two first-morning void urine UACR measurements with samples collected on two separate occasions within a 4-day period. The effect of BMS-813160 on urinary albumin excretion as measured by UACR values in participants with diabetic kidney disease after 12 weeks of treatment was assessed. The model included treatment group as a main effect, and the log of baseline UACR values, as well as baseline values of eGFR, blood pressure, blood glucose and lipid levels, as covariates.

Full Information

First Posted
December 17, 2012
Last Updated
July 26, 2019
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT01752985
Brief Title
Study to Evaluate the Effects of BMS-813160 on Protein Loss in the Urine of Subjects With Type 2 Diabetes and Diabetic Kidney Disease
Official Title
A Double-Blind, Placebo-Controlled, Randomized, Two-stage, Parallel-Group, Adaptive Design Phase 2a Study to Evaluate the Effects of BMS-813160 in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (DKD) Who Have Residual Macroalbuminuria Despite Treatment With an Inhibitor of the Renin-Angiotensin System
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Terminated
Why Stopped
Business objectives have changed
Study Start Date
March 18, 2013 (Actual)
Primary Completion Date
June 30, 2015 (Actual)
Study Completion Date
June 30, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine whether BMS-813160 will reduce the amount of protein loss in the urine of subjects with type 2 diabetes and diabetic kidney disease

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
319 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: BMS-813160 150 mg & Placebo matching with BMS-813160
Arm Type
Experimental
Arm Description
BMS-813160 150 mg capsules by mouth in AM and Placebo matching with BMS-813160 in PM for 12 weeks
Arm Title
Arm B: BMS-813160 300 mg
Arm Type
Experimental
Arm Description
BMS-813160 300 mg capsules by mouth twice daily for 12 weeks
Arm Title
Arm C: Placebo matching with BMS-813160
Arm Type
Placebo Comparator
Arm Description
Placebo matching with BMS-813160 0 mg capsules by mouth twice daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
BMS-813160
Intervention Type
Drug
Intervention Name(s)
Placebo matching with BMS-813160
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) Across 12 Weeks of Treatment With BMS-813160
Description
The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples. UACR was calculated as the geometric mean of two first-morning void urine UACR measurements with samples collected on two separate occasions within a 4-day period.
Time Frame
Baseline, Weeks 2, 4, 8, 12, and 16 (Follow-up)
Secondary Outcome Measure Information:
Title
Number of Participants With Serious Adverse Events (SAEs), Who Died and With Other (Not Including Serious) Adverse Events
Description
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, or a congenital anomaly, or a medically important event.
Time Frame
From the date of subject's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Title
Number of Participants With Out-of-Range Electrocardiogram (ECG) Interval
Description
12-lead ECGs were performed before and 1 hour after dosing at Weeks 0, 2 and 4. ECGs were recorded after the participant has been supine for at least 5 minutes. The PR interval was defined as the beginning of the P wave to the beginning of the QRS complex, and represents the time taken by electrical impulse to travel from the sinus node through the atrioventricular (AV) node. The QRS complex represented the rapid depolarization of the right and left ventricles. The QT interval was defined as the time from the start of the Q wave to the end of the T wave, and represents the time taken for ventricular depolarization and repolarization. Participants were evaluated for abnormal ECG intervals. Criteria's for abnormality were PR >200, QRS >120, QT >500, QTcF >450, Change From Baseline >30 milliseconds (msec).
Time Frame
Baseline up to Week 16
Title
Trough Observed Plasma Concentration (Ctrough) of BMS-813160
Description
Ctrough is the minimum estimated plasma concentration at steady state.
Time Frame
Pre-dose at Week 2, 4, 8, 12 and 0.5, 1, 2, 4, and 6 hours post-dose at Week 12
Title
Area Under The Plasma Concentration-Time Curve From Time Zero to 6 Hours Post-Dose [AUC(0-6 h)]
Description
AUC(0-6 h) is the area under the plasma concentration-time curve from pre-dose (0 h) to 6 h post-dose.
Time Frame
Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Week 12
Title
Renal Clearance (CLr) of BMS-813160
Description
CLr was calculated by dividing the total amount excreted in the urine from 0 to 6 hours by the area under the plasma concentration-time curve from time zero extrapolated to infinite time. The renal function was classified based on estimated glomerular filtration rate as normal (>=90 mL/min/1.73 m^2), mildly impaired (60-89 mL/min/1.73 m^2), moderately impaired stage 3A (45-59 mL/min/1.73 m^2), and moderately impaired stage 3B (30-44 L/min/1.73 m^2).
Time Frame
Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Week 12
Title
Dose-Response Relationship Using Change in Baseline Urinary Albumin-to-Creatinine Ratio (UACR) Across 12 Weeks of Treatment
Description
The presence of albumin in the urine (macroalbuminuria) is a marker of kidney disease. Albumin and creatinine concentrations were obtained from spot urine samples. UACR was calculated as the geometric mean of two first-morning void urine UACR measurements with samples collected on two separate occasions within a 4-day period. The effect of BMS-813160 on urinary albumin excretion as measured by UACR values in participants with diabetic kidney disease after 12 weeks of treatment was assessed. The model included treatment group as a main effect, and the log of baseline UACR values, as well as baseline values of eGFR, blood pressure, blood glucose and lipid levels, as covariates.
Time Frame
Baseline, Weeks 2, 4, 8 and 12

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Clinical diagnosis of type 2 diabetes mellitus with macroalbuminuria (UACR between 200 and 3500 mg/g) Background angiotensin converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) therapy Exclusion Criteria: Clinical diagnosis of type 1 diabetes Unstable cardiovascular, metabolic, or other chronic disease status Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 High risk of infection or immune compromise Clinically significant ECG conduction abnormalities Drugs with significant potential to affect BMS-813160 exposure
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
Uab Hospital
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Univ Of Al At Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Akdhc Medical Research Services Llc
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85012
Country
United States
Facility Name
Academic Medical Research Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90022
Country
United States
Facility Name
Ucla
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
Providence Clinical Research
City
North Hollywood
State/Province
California
ZIP/Postal Code
91606
Country
United States
Facility Name
Diabetes Medical Center Of California
City
Northridge
State/Province
California
ZIP/Postal Code
91325
Country
United States
Facility Name
Diablo Clinical Research, Inc.
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
George Washington University Medical Faculty Associates
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
All Medical Research, Llc
City
Cooper City
State/Province
Florida
ZIP/Postal Code
33024
Country
United States
Facility Name
International Research Associates, Llc
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
Genesis Clinical Research, Inc.
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
Facility Name
Emory University School Of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Endocrine Research Solutions, Inc.
City
Roswell
State/Province
Georgia
ZIP/Postal Code
30076
Country
United States
Facility Name
John H. Stroger, Jr. Hospital Of Cook County
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Research By Design, Llc
City
Evergreen Park
State/Province
Illinois
ZIP/Postal Code
60805
Country
United States
Facility Name
St Louis Center Clinl Res
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63128
Country
United States
Facility Name
St. Louis Center For Clinical Research
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63128
Country
United States
Facility Name
Va Nebraska-Western Iowa Health Care System (Nwihcs)
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68105
Country
United States
Facility Name
Southern Nh Diab And Endo
City
Nashua
State/Province
New Hampshire
ZIP/Postal Code
03063
Country
United States
Facility Name
Premier Research, Inc.
City
Trenton
State/Province
New Jersey
ZIP/Postal Code
08611
Country
United States
Facility Name
Albany Medical College
City
Albany
State/Province
New York
ZIP/Postal Code
12206
Country
United States
Facility Name
The Endocrine Group Llp
City
Albany
State/Province
New York
ZIP/Postal Code
12206
Country
United States
Facility Name
Nephrology Associates
City
Flushing
State/Province
New York
ZIP/Postal Code
11355
Country
United States
Facility Name
Medispect Medical Research, Llc
City
Boone
State/Province
North Carolina
ZIP/Postal Code
28607
Country
United States
Facility Name
Metrolina Internal Medicine
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
The Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Paramount Medical Research & Consulting, Llc
City
Middleburg Heights
State/Province
Ohio
ZIP/Postal Code
44130
Country
United States
Facility Name
Physician Research, Inc.
City
Zanesville
State/Province
Ohio
ZIP/Postal Code
43701
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Piedmont Health Grp, Llc-Twr Pt Res Ctr
City
Hodges
State/Province
South Carolina
ZIP/Postal Code
29653
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-1371
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Doctors Hospital At Renaissance
City
Edinburg
State/Province
Texas
ZIP/Postal Code
78539
Country
United States
Facility Name
San Antonio Military Medical Center
City
Fort Sam Houston
State/Province
Texas
ZIP/Postal Code
78234-6200
Country
United States
Facility Name
San Antonio Military Medical Center
City
Fort Sam Houston
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
Facility Name
Northeast Clinical Research Of San Antonio, Llc
City
Schertz
State/Province
Texas
ZIP/Postal Code
78154
Country
United States
Facility Name
Burke Internal Medicine And Research
City
Burke
State/Province
Virginia
ZIP/Postal Code
22015
Country
United States
Facility Name
Virginia Endocrinology Research
City
Chesapeake
State/Province
Virginia
ZIP/Postal Code
23321
Country
United States
Facility Name
Manassas Clinical Research Center
City
Manassas
State/Province
Virginia
ZIP/Postal Code
20110
Country
United States
Facility Name
Mcguire Va Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
Health Sciences Centre Diabetes Research Centre
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3A 1R9
Country
Canada
Facility Name
Eastern Health Sciences Center
City
St. John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1B 3V6
Country
Canada
Facility Name
Aggarwal And Associates
City
Brampton
State/Province
Ontario
ZIP/Postal Code
L6T 0G1
Country
Canada
Facility Name
Clinical Research Solutions, Inc
City
Kitchener
State/Province
Ontario
ZIP/Postal Code
N2H 5Z8
Country
Canada
Facility Name
Lmc Diabetes & Endocrinology (Thornhill)
City
Thornhill
State/Province
Ontario
ZIP/Postal Code
L4J 8L7
Country
Canada
Facility Name
Lmc Diabetes & Endocrinology (Bayview)
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4G 3E8
Country
Canada
Facility Name
Centre De Recherche Clinique De Laval
City
Laval
State/Province
Quebec
ZIP/Postal Code
H7T 2P5
Country
Canada
Facility Name
Recherche Gcp Research
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2R 1V6
Country
Canada
Facility Name
Local Institution
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Local Institution
City
Frederiksberg
ZIP/Postal Code
2000
Country
Denmark
Facility Name
Local Institution
City
Gentofte
ZIP/Postal Code
2820
Country
Denmark
Facility Name
Local Institution
City
Hillerod
ZIP/Postal Code
3400
Country
Denmark
Facility Name
Local Institution
City
Holstebro
ZIP/Postal Code
7500
Country
Denmark
Facility Name
Local Institution
City
Amiens Cedex 1
ZIP/Postal Code
80054
Country
France
Facility Name
Local Institution
City
Grenoble Cedex 9
ZIP/Postal Code
F38043
Country
France
Facility Name
Local Institution
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Local Institution
City
Paris
ZIP/Postal Code
75877
Country
France
Facility Name
Local Institution
City
Poitiers Cedex
ZIP/Postal Code
86021
Country
France
Facility Name
Local Institution
City
Tours Cedex 09
ZIP/Postal Code
37044
Country
France

12. IPD Sharing Statement

Links:
URL
http://bms.com/studyconnect/Pages/home.aspx
Description
BMS Clinical Trial Patient Recruiting

Learn more about this trial

Study to Evaluate the Effects of BMS-813160 on Protein Loss in the Urine of Subjects With Type 2 Diabetes and Diabetic Kidney Disease

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