Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan

Chronic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01424319
• Other study ID #: M12-812
• Status: Completed
• Phase: Phase 2
• First received: August 25, 2011
• Last updated: August 25, 2017
• Start date: August 2011
• Est. completion date: July 2012

Study information

• Verified date: August 2017
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Albuminuria
• Chronic Kidney Disease
• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Atrasentan low dose group
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.
• Atrasentan high dose group
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.
• Atrasentan placebo group
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.

Locations

Country	Name	City	State
Japan	Site Reference ID/Investigator# 62022	Azumino
Japan	Site Reference ID/Investigator# 58124	Chiba
Japan	Site Reference ID/Investigator# 57486	Fujisawa
Japan	Site Reference ID/Investigator# 55097	Ibaraki
Japan	Site Reference ID/Investigator# 56982	Ina
Japan	Site Reference ID/Investigator# 55093	Kawagoe
Japan	Site Reference ID/Investigator# 57485	Kawasaki
Japan	Site Reference ID/Investigator# 55092	Koriyama
Japan	Site Reference ID/Investigator# 56524	Matsumoto
Japan	Site Reference ID/Investigator# 57242	Nagano
Japan	Site Reference ID/Investigator# 55781	Nagoya
Japan	Site Reference ID/Investigator# 60965	Nagoya-city
Japan	Site Reference ID/Investigator# 55304	Suwa
Japan	Site Reference ID/Investigator# 59474	Tokyo
Japan	Site Reference ID/Investigator# 59967	Ueda
Japan	Site Reference ID/Investigator# 55095	Yokohama
Japan	Site Reference ID/Investigator# 57484	Yokohama
Japan	Site Reference ID/Investigator# 59842	Yokohama

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

Country where clinical trial is conducted

Japan, 

References & Publications (2)

de Zeeuw D, Coll B, Andress D, Brennan JJ, Tang H, Houser M, Correa-Rotter R, Kohan D, Lambers Heerspink HJ, Makino H, Perkovic V, Pritchett Y, Remuzzi G, Tobe SW, Toto R, Viberti G, Parving HH. The endothelin antagonist atrasentan lowers residual albumin — View Citation

Kohan DE, Lambers Heerspink HJ, Coll B, Andress D, Brennan JJ, Kitzman DW, Correa-Rotter R, Makino H, Perkovic V, Hou FF, Remuzzi G, Tobe SW, Toto R, Parving HH, de Zeeuw D. Predictors of Atrasentan-Associated Fluid Retention and Change in Albuminuria in — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change from baseline to each post-baseline visit in log-transformed UACR (urinary albumin to creatinine ratio)		Up to Week 12
Secondary	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
Secondary	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
Secondary	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