Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan

Study Overview
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Brief Summary
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Prospective, randomized, double-blind, placebo controlled, 12-week, multicenter study. The objective of the study is to evaluate the efficacy and safety of once daily administration of atrasentan tablets compared to placebo in reducing residual albuminuria in Japanese Type 2 diabetic patients with nephropathy who are treated with the maximum tolerated labeled dose for hypertension of a RAS (renin angiotensin system) inhibitor.

Official Title
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Reducing Residual Albuminuria in Subjects With Diabetes & Nephropathy With Atrasentan - A Phase 2b, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety & Efficacy in Japanese Subjects

Conditions
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Chronic Kidney Disease, Diabetic Nephropathy

Intervention / Treatment
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* Drug: Atrasentan low dose group
* Drug: Atrasentan high dose group
* Drug: Atrasentan placebo group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has Type 2 diabetes and has been treated with at least one anti-hyperglycemic medication within the 12 months prior to the screening period. Patient is receiving a maximum tolerated labeled dose of an ACEi (Angiotensin Converting Enzyme inhibitor) or ARB (Angiotensin II Receptor Blocker)(Renin Angiotensin System (RAS) inhibitor). Estimated GFR (Glomerular Filtration Rate) is greater than or equal to 30 and less than or equal to 75 mL/min/1.73m2 by the CKD (chronic kidney disease) Epidemiology Collaboration (EPI) formula. UACR (Urinary Albumin to Creatinine Ratio) is greater than or equal to 200 mg/g as determined by the geometric mean of the three morning void urine specimens obtained at Run-in period. Serum albumin is greater than or equal to 3.0 g/dL. BNP (B-type Natriuretic Peptide) is less than or equal to 200 pg/mL. SBP (Systolic Blood Pressure) is greater than or equal to 110 mmHg and less than or equal to 160 mmHg. HbA1c (Glucosylated Hemoglobin A1c) is less than or equal to 12% and serum potassium is less than or equal to 5.5 mEq/L. Exclusion Criteria: Patient has a history of moderate or severe edema, facial edema unrelated to trauma, or a history of myxedema in the prior 6 months to screening. Patient is receiving loop diuretics greater than or equal to 120 mg QD (Once Daily) of furosemide or greater than or equal to 3.0 mg QD (Once Daily) of bumetanide or greater than or equal to 150 mg QD (Once Daily) of ethacrynic acid or greater than or equal to 60 mg QD (Once Daily) of torasemide. Patient has a documented history of Stage C or Stage D heart failure, defined ACC/AHA (American College of Cardiology/ American Heart Association Practice Guidelines). Patient is receiving any of a combination of an ACEi (Angiotensin Converting Enzyme inhibitor) and ARB (Angiotensin II Receptor Blocker) or rosiglitazone or aliskiren or an aldosterone antagonist and patient is receiving pioglitazone and edema is present.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABT-627, Low dose<br> | Drug: Atrasentan low dose group<br>* Subjects will take two tablets daily of one of those which are atrasentan low dose, atrasentan high dose or atrasentan placebo for 12 weeks during the treatment period.<br>|
| Experimental: ABT-627, High dose<br> | Drug: Atrasentan high dose group<br>* Subjects will take two tablets daily of one of those which are atrasentan low dose, atrasentan high dose or atrasentan placebo for 12 weeks during the treatment period.<br>|
| Placebo Comparator: ABT-627, Placebo<br> | Drug: Atrasentan placebo group<br>* Subjects will take two tablets daily of one of those which are atrasentan low dose, atrasentan high dose or atrasentan placebo for 12 weeks during the treatment period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change from baseline to each post-baseline visit in log-transformed UACR (urinary albumin to creatinine ratio) |  | Up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects who have achieved at least 30% reduction on UACR (Urinary Albumin to Creatinine Ratio) who have not had any form of treatment-emergent edema with moderate or severe severity. |  | Up to Week 12 | 
| The change from baseline to each post-baseline visit on log-transformed UACR (Urinary Albumin to Creatinine Ratio) and estimated GFR (Glomerular Filtration Rate) |  | Up to Week 12 | 
| The proportion of subjects who achieve various percent of reduction in UACR (Urinary Albumin to Creatinine Ratio) from baseline to final |  | Up to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endothelin Receptor Antagonists, Proteinuria