Study to Evaluate the Effects of BMS-813160 on Protein Loss in the Urine of Subjects With Type 2 Diabetes and Diabetic Kidney Disease
- Conditions
- Diabetic Kidney Disease
- Interventions
- Drug: Placebo matching with BMS-813160
- Registration Number
- NCT01752985
- Lead Sponsor
- Bristol-Myers Squibb
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 319
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm C: Placebo matching with BMS-813160 Placebo matching with BMS-813160 Placebo matching with BMS-813160 0 mg capsules by mouth twice daily for 12 weeks Arm A: BMS-813160 150 mg & Placebo matching with BMS-813160 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 Arm B: BMS-813160 300 mg BMS-813160 BMS-813160 300 mg capsules by mouth twice daily for 12 weeks Arm A: BMS-813160 150 mg & Placebo matching with BMS-813160 BMS-813160 BMS-813160 150 mg capsules by mouth in AM and Placebo matching with BMS-813160 in PM for 12 weeks
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) Across 12 Weeks of Treatment With BMS-813160 Baseline, Weeks 2, 4, 8, 12, and 16 (Follow-up) 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
Name Time Method Number of Participants With Serious Adverse Events (SAEs), Who Died and With Other (Not Including Serious) Adverse Events From the date of subject's written consent until 30 days post discontinuation of dosing, assessed up to 26 months 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 Baseline up to Week 16 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).
Area Under The Plasma Concentration-Time Curve From Time Zero to 6 Hours Post-Dose [AUC(0-6 h)] Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Week 12 AUC(0-6 h) is the area under the plasma concentration-time curve from pre-dose (0 h) to 6 h post-dose.
Trough Observed Plasma Concentration (Ctrough) of BMS-813160 Pre-dose at Week 2, 4, 8, 12 and 0.5, 1, 2, 4, and 6 hours post-dose at Week 12 Ctrough is the minimum estimated plasma concentration at steady state.
Renal Clearance (CLr) of BMS-813160 Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Week 12 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 Baseline, Weeks 2, 4, 8 and 12 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.
Trial Locations
- Locations (50)
Academic Medical Research Institute
🇺🇸Los Angeles, California, United States
Recherche Gcp Research
🇨🇦Montreal, Quebec, Canada
Eastern Health Sciences Center
🇨🇦St. John's, Newfoundland and Labrador, Canada
Metrolina Internal Medicine
🇺🇸Charlotte, North Carolina, United States
Physician Research, Inc.
🇺🇸Zanesville, Ohio, United States
International Research Associates, Llc
🇺🇸Hialeah, Florida, United States
Nephrology Associates
🇺🇸Flushing, New York, United States
Diablo Clinical Research, Inc.
🇺🇸Walnut Creek, California, United States
All Medical Research, Llc
🇺🇸Cooper City, Florida, United States
Medispect Medical Research, Llc
🇺🇸Boone, North Carolina, United States
Emory University School Of Medicine
🇺🇸Atlanta, Georgia, United States
Endocrine Research Solutions, Inc.
🇺🇸Roswell, Georgia, United States
Albany Medical College
🇺🇸Albany, New York, United States
Doctors Hospital At Renaissance
🇺🇸Edinburg, Texas, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
The Endocrine Group Llp
🇺🇸Albany, New York, United States
Centre De Recherche Clinique De Laval
🇨🇦Laval, Quebec, Canada
Research By Design, Llc
🇺🇸Evergreen Park, Illinois, United States
St. Louis Center For Clinical Research
🇺🇸Saint Louis, Missouri, United States
Southern Nh Diab And Endo
🇺🇸Nashua, New Hampshire, United States
Lmc Diabetes & Endocrinology (Bayview)
🇨🇦Toronto, Ontario, Canada
John H. Stroger, Jr. Hospital Of Cook County
🇺🇸Chicago, Illinois, United States
Health Sciences Centre Diabetes Research Centre
🇨🇦Winnipeg, Manitoba, Canada
George Washington University Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
St Louis Center Clinl Res
🇺🇸Saint Louis, Missouri, United States
Premier Research, Inc.
🇺🇸Trenton, New Jersey, United States
Piedmont Health Grp, Llc-Twr Pt Res Ctr
🇺🇸Hodges, South Carolina, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Local Institution
🇫🇷Tours Cedex 09, France
Northeast Clinical Research Of San Antonio, Llc
🇺🇸Schertz, Texas, United States
Lmc Diabetes & Endocrinology (Thornhill)
🇨🇦Thornhill, Ontario, Canada
Virginia Endocrinology Research
🇺🇸Chesapeake, Virginia, United States
Clinical Research Solutions, Inc
🇨🇦Kitchener, Ontario, Canada
Aggarwal And Associates
🇨🇦Brampton, Ontario, Canada
San Antonio Military Medical Center
🇺🇸Fort Sam Houston, Texas, United States
Paramount Medical Research & Consulting, Llc
🇺🇸Middleburg Heights, Ohio, United States
Burke Internal Medicine And Research
🇺🇸Burke, Virginia, United States
Manassas Clinical Research Center
🇺🇸Manassas, Virginia, United States
Ucla
🇺🇸Los Angeles, California, United States
Providence Clinical Research
🇺🇸North Hollywood, California, United States
Diabetes Medical Center Of California
🇺🇸Northridge, California, United States
Uab Hospital
🇺🇸Birmingham, Alabama, United States
Univ Of Al At Birmingham
🇺🇸Birmingham, Alabama, United States
Akdhc Medical Research Services Llc
🇺🇸Phoenix, Arizona, United States
Genesis Clinical Research, Inc.
🇺🇸Tampa, Florida, United States
Va Nebraska-Western Iowa Health Care System (Nwihcs)
🇺🇸Omaha, Nebraska, United States
Duke University
🇺🇸Durham, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Mcguire Va Medical Center
🇺🇸Richmond, Virginia, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States