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

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

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

Study Overview

• Status: Terminated
• Conditions: Diabetic Kidney Disease
• Intervention / Treatment: Drug: BMS-813160; Drug: Placebo matching with BMS-813160

• Study Type: Interventional
• Enrollment (Actual): 319
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Centre Diabetes Research Centre
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Eastern Health Sciences Center
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal And Associates
    • Kitchener, Ontario, Canada, N2H 5Z8
      • Clinical Research Solutions, Inc
    • Thornhill, Ontario, Canada, L4J 8L7
      • Lmc Diabetes & Endocrinology (Thornhill)
    • Toronto, Ontario, Canada, M4G 3E8
      • Lmc Diabetes & Endocrinology (Bayview)
  • Quebec
    • Laval, Quebec, Canada, H7T 2P5
      • Centre de Recherche Clinique de Laval
    • Montreal, Quebec, Canada, H3T 1E2
      • Local Institution
    • Montreal, Quebec, Canada, H2R 1V6
      • Recherche GCP Research
• Denmark
  • Frederiksberg, Denmark, 2000
    • Local Institution
  • Gentofte, Denmark, 2820
    • Local Institution
  • Hillerod, Denmark, 3400
    • Local Institution
  • Holstebro, Denmark, 7500
    • Local Institution
• France
  • Amiens Cedex 1, France, 80054
    • Local Institution
  • Grenoble Cedex 9, France, F38043
    • Local Institution
  • Nantes Cedex 1, France, 44093
    • Local Institution
  • Paris, France, 75877
    • Local Institution
  • Poitiers Cedex, France, 86021
    • Local Institution
  • Tours Cedex 09, France, 37044
    • Local Institution
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB Hospital
    • Birmingham, Alabama, United States, 35294
      • Univ Of Al At Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Akdhc Medical Research Services Llc
  • California
    • Los Angeles, California, United States, 90022
      • Academic Medical Research Institute
    • Los Angeles, California, United States, 90025
      • UCLA
    • North Hollywood, California, United States, 91606
      • Providence Clinical Research
    • Northridge, California, United States, 91325
      • Diabetes Medical Center of California
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University Medical Faculty Associates
  • Florida
    • Cooper City, Florida, United States, 33024
      • ALL Medical Research, LLC
    • Hialeah, Florida, United States, 33012
      • International Research Associates, LLC
    • Tampa, Florida, United States, 33614
      • Genesis Clinical Research, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University School of Medicine
    • Roswell, Georgia, United States, 30076
      • Endocrine Research Solutions, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60612
      • John H. Stroger, Jr. Hospital of Cook County
    • Evergreen Park, Illinois, United States, 60805
      • Research by Design, LLC
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • St. Louis Center for Clinical Research
    • Saint Louis, Missouri, United States, 63128
      • St Louis Center Clinl Res
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • Va Nebraska-Western Iowa Health Care System (Nwihcs)
  • New Hampshire
    • Nashua, New Hampshire, United States, 03063
      • Southern Nh Diab And Endo
  • New Jersey
    • Trenton, New Jersey, United States, 08611
      • Premier Research, Inc.
  • New York
    • Albany, New York, United States, 12206
      • Albany Medical College
    • Albany, New York, United States, 12206
      • The Endocrine Group Llp
    • Flushing, New York, United States, 11355
      • Nephrology Associates
  • North Carolina
    • Boone, North Carolina, United States, 28607
      • Medispect Medical Research, Llc
    • Charlotte, North Carolina, United States, 28204
      • Metrolina Internal Medicine
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
    • Middleburg Heights, Ohio, United States, 44130
      • Paramount Medical Research & Consulting, LLC
    • Zanesville, Ohio, United States, 43701
      • Physician Research, Inc.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Hodges, South Carolina, United States, 29653
      • Piedmont Health Grp, Llc-Twr Pt Res Ctr
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37232-1371
      • Vanderbilt University Medical Center
  • Texas
    • Edinburg, Texas, United States, 78539
      • Doctors Hospital at Renaissance
    • Fort Sam Houston, Texas, United States, 78234
      • San Antonio Military Medical Center
    • Fort Sam Houston, Texas, United States, 78234-6200
      • San Antonio Military Medical Center
    • Schertz, Texas, United States, 78154
      • Northeast Clinical Research of San Antonio, LLC
  • Virginia
    • Burke, Virginia, United States, 22015
      • Burke Internal Medicine and Research
    • Chesapeake, Virginia, United States, 23321
      • Virginia Endocrinology Research
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center
    • Richmond, Virginia, United States, 23249
      • McGuire VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: BMS-813160 150 mg & Placebo matching with BMS-813160; BMS-813160 150 mg capsules by mouth in AM and Placebo matching with BMS-813160 in PM for 12 weeks	Drug: BMS-813160; Drug: Placebo matching with BMS-813160
Experimental: Arm B: BMS-813160 300 mg; BMS-813160 300 mg capsules by mouth twice daily for 12 weeks	Drug: BMS-813160
Placebo Comparator: Arm C: Placebo matching with BMS-813160; Placebo matching with BMS-813160 0 mg capsules by mouth twice daily for 12 weeks	Drug: Placebo matching with BMS-813160

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2013
• Primary Completion (Actual): June 30, 2015
• Study Completion (Actual): June 30, 2015

Study Registration Dates

• First Submitted: December 17, 2012
• First Submitted That Met QC Criteria: December 17, 2012
• First Posted (Estimate): December 19, 2012

Study Record Updates

• Last Update Posted (Actual): July 30, 2019
• Last Update Submitted That Met QC Criteria: July 26, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: CV202-010; 2012-005093-54 (EudraCT Number)