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

Diabetic Kidney Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01752985
• Other study ID #: CV202-010
• Secondary ID: 2012-005093-54
• Status: Terminated
• Phase: Phase 2
• Start date: March 18, 2013
• Est. completion date: June 30, 2015

Study information

• Verified date: July 2019
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 319
• Est. completion date: June 30, 2015
• Est. primary completion date: June 30, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Kidney Disease
• Diabetic Nephropathies
• Kidney Diseases

Intervention

Drug:
• BMS-813160

• Placebo matching with BMS-813160

Locations

Country	Name	City	State
Canada	Aggarwal And Associates	Brampton	Ontario
Canada	Clinical Research Solutions, Inc	Kitchener	Ontario
Canada	Centre De Recherche Clinique De Laval	Laval	Quebec
Canada	Local Institution	Montreal	Quebec
Canada	Recherche Gcp Research	Montreal	Quebec
Canada	Eastern Health Sciences Center	St. John's	Newfoundland and Labrador
Canada	Lmc Diabetes & Endocrinology (Thornhill)	Thornhill	Ontario
Canada	Lmc Diabetes & Endocrinology (Bayview)	Toronto	Ontario
Canada	Health Sciences Centre Diabetes Research Centre	Winnipeg	Manitoba
Denmark	Local Institution	Frederiksberg
Denmark	Local Institution	Gentofte
Denmark	Local Institution	Hillerod
Denmark	Local Institution	Holstebro
France	Local Institution	Amiens Cedex 1
France	Local Institution	Grenoble Cedex 9
France	Local Institution	Nantes Cedex 1
France	Local Institution	Paris
France	Local Institution	Poitiers Cedex
France	Local Institution	Tours Cedex 09
United States	Albany Medical College	Albany	New York
United States	The Endocrine Group Llp	Albany	New York
United States	Emory University School Of Medicine	Atlanta	Georgia
United States	Uab Hospital	Birmingham	Alabama
United States	Univ Of Al At Birmingham	Birmingham	Alabama
United States	Medispect Medical Research, Llc	Boone	North Carolina
United States	Burke Internal Medicine And Research	Burke	Virginia
United States	Metrolina Internal Medicine	Charlotte	North Carolina
United States	Virginia Endocrinology Research	Chesapeake	Virginia
United States	John H. Stroger, Jr. Hospital Of Cook County	Chicago	Illinois
United States	Ohio State University Medical Center	Columbus	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	All Medical Research, Llc	Cooper City	Florida
United States	Duke University	Durham	North Carolina
United States	Doctors Hospital At Renaissance	Edinburg	Texas
United States	Research By Design, Llc	Evergreen Park	Illinois
United States	Nephrology Associates	Flushing	New York
United States	San Antonio Military Medical Center	Fort Sam Houston	Texas
United States	San Antonio Military Medical Center	Fort Sam Houston	Texas
United States	International Research Associates, Llc	Hialeah	Florida
United States	Piedmont Health Grp, Llc-Twr Pt Res Ctr	Hodges	South Carolina
United States	Academic Medical Research Institute	Los Angeles	California
United States	Ucla	Los Angeles	California
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Paramount Medical Research & Consulting, Llc	Middleburg Heights	Ohio
United States	Southern Nh Diab And Endo	Nashua	New Hampshire
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Providence Clinical Research	North Hollywood	California
United States	Diabetes Medical Center Of California	Northridge	California
United States	Va Nebraska-Western Iowa Health Care System (Nwihcs)	Omaha	Nebraska
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Akdhc Medical Research Services Llc	Phoenix	Arizona
United States	Mcguire Va Medical Center	Richmond	Virginia
United States	Endocrine Research Solutions, Inc.	Roswell	Georgia
United States	St Louis Center Clinl Res	Saint Louis	Missouri
United States	St. Louis Center For Clinical Research	Saint Louis	Missouri
United States	Northeast Clinical Research Of San Antonio, Llc	Schertz	Texas
United States	Genesis Clinical Research, Inc.	Tampa	Florida
United States	Premier Research, Inc.	Trenton	New Jersey
United States	Diablo Clinical Research, Inc.	Walnut Creek	California
United States	George Washington University Medical Faculty Associates	Washington	District of Columbia
United States	Physician Research, Inc.	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Weeks 2, 4, 8, 12, and 16 (Follow-up)
Secondary	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.	From the date of subject's written consent until 30 days post discontinuation of dosing, assessed up to 26 months
Secondary	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).	Baseline up to Week 16
Secondary	Trough Observed Plasma Concentration (Ctrough) of BMS-813160	Ctrough is the minimum estimated plasma concentration at steady state.	Pre-dose at Week 2, 4, 8, 12 and 0.5, 1, 2, 4, and 6 hours post-dose at Week 12
Secondary	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.	Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Week 12
Secondary	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).	Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Week 12
Secondary	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.	Baseline, Weeks 2, 4, 8 and 12

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