Clinical trial NCT01424319: Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Kidney Disease
Diabetic Nephropathy
Keywords: Endothelin Receptor Antagonists
Proteinuria
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2011-08-29
Enrollment: 58
Sex: ALL
Minimum age (years): 20
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: The change from baseline to each post-baseline visit in log-transformed UACR (urinary albumin to creatinine ratio)
timeFrame: Up to Week 12
Secondary outcomes:
measure: 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.
timeFrame: Up to Week 12
measure: The change from baseline to each post-baseline visit on log-transformed UACR (Urinary Albumin to Creatinine Ratio) and estimated GFR (Glomerular Filtration Rate)
timeFrame: Up to Week 12
measure: The proportion of subjects who achieve various percent of reduction in UACR (Urinary Albumin to Creatinine Ratio) from baseline to final
timeFrame: Up to Week 12
Other outcomes:
Locations:
city: Azumino
country: Japan
facility: Site Reference ID/Investigator# 62022
city: Chiba
country: Japan
facility: Site Reference ID/Investigator# 58124
city: Fujisawa
country: Japan
facility: Site Reference ID/Investigator# 57486
city: Ibaraki
country: Japan
facility: Site Reference ID/Investigator# 55097
city: Ina
country: Japan
facility: Site Reference ID/Investigator# 56982
city: Kawagoe
country: Japan
facility: Site Reference ID/Investigator# 55093
city: Kawasaki
country: Japan
facility: Site Reference ID/Investigator# 57485
city: Koriyama
country: Japan
facility: Site Reference ID/Investigator# 55092
city: Matsumoto
country: Japan
facility: Site Reference ID/Investigator# 56524
city: Nagano
country: Japan
facility: Site Reference ID/Investigator# 57242
city: Nagoya-city
country: Japan
facility: Site Reference ID/Investigator# 60965
city: Nagoya
country: Japan
facility: Site Reference ID/Investigator# 55781
city: Suwa
country: Japan
facility: Site Reference ID/Investigator# 55304
city: Tokyo
country: Japan
facility: Site Reference ID/Investigator# 59474
city: Ueda
country: Japan
facility: Site Reference ID/Investigator# 59967
city: Yokohama
country: Japan
facility: Site Reference ID/Investigator# 55095
city: Yokohama
country: Japan
facility: Site Reference ID/Investigator# 57484
city: Yokohama
country: Japan
facility: Site Reference ID/Investigator# 59842
Study officials:
affiliation: Abbott Japan Co.,Ltd
name: Mosleh UDDIN, PharmD
role: STUDY_DIRECTOR
References:
citation: 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 albuminuria in patients with type 2 diabetic nephropathy. J Am Soc Nephrol. 2014 May;25(5):1083-93. doi: 10.1681/ASN.2013080830. Epub 2014 Apr 10.
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 Patients with Diabetic Nephropathy. Clin J Am Soc Nephrol. 2015 Sep 4;10(9):1568-74. doi: 10.2215/CJN.00570115. Epub 2015 Jul 7.
citation: Lin CW, Mostafa NM, L Andress D, J Brennan J, Klein CE, Awni WM. Relationship Between Atrasentan Concentrations and Urinary Albumin to Creatinine Ratio in Western and Japanese Patients With Diabetic Nephropathy. Clin Ther. 2018 Feb;40(2):242-251. doi: 10.1016/j.clinthera.2017.07.011. Epub 2017 Jul 27.