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

Study Overview
=================
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

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

Conditions
-----------------
Diabetic Kidney Disease

Intervention / Treatment
-----------------
* Drug: BMS-813160
* Drug: Placebo matching with BMS-813160


Participation Criteria
=================
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
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

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 |