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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

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ClinicalTrials.gov Identifier: NCT01752985
Recruitment Status : Terminated (Business objectives have changed)
First Posted : December 19, 2012
Results First Posted : June 25, 2019
Last Update Posted : July 30, 2019
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Diabetic Kidney Disease Drug: BMS-813160 Drug: Placebo matching with BMS-813160 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 319 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : March 18, 2013
Actual Primary Completion Date : June 30, 2015
Actual Study Completion Date : June 30, 2015

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. Percent Change From Baseline in Urinary Albumin-to-Creatinine Ratio (UACR) Across 12 Weeks of Treatment With BMS-813160 [ Time Frame: 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 :
  1. Number of Participants With Serious Adverse Events (SAEs), Who Died and With Other (Not Including Serious) Adverse Events [ Time Frame: 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.

  2. Number of Participants With Out-of-Range Electrocardiogram (ECG) Interval [ Time Frame: 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).

  3. Trough Observed Plasma Concentration (Ctrough) of BMS-813160 [ Time Frame: 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.

  4. Area Under The Plasma Concentration-Time Curve From Time Zero to 6 Hours Post-Dose [AUC(0-6 h)] [ Time Frame: 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.

  5. Renal Clearance (CLr) of BMS-813160 [ Time Frame: 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).

  6. Dose-Response Relationship Using Change in Baseline Urinary Albumin-to-Creatinine Ratio (UACR) Across 12 Weeks of Treatment [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01752985


Locations
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Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Additional Information:
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01752985    
Other Study ID Numbers: CV202-010
2012-005093-54 ( EudraCT Number )
First Posted: December 19, 2012    Key Record Dates
Results First Posted: June 25, 2019
Last Update Posted: July 30, 2019
Last Verified: July 2019
Additional relevant MeSH terms:
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Kidney Diseases
Diabetic Nephropathies
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases