Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan

NCT ID: NCT01424319

Last Updated: 2017-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2012-07-31

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.

Conditions

Chronic Kidney Disease; Diabetic Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ABT-627, Low dose

Group Type: EXPERIMENTAL

Atrasentan low dose group

Intervention Type: DRUG

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.

ABT-627, High dose

Group Type: EXPERIMENTAL

Atrasentan high dose group

Intervention Type: DRUG

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.

ABT-627, Placebo

Group Type: PLACEBO_COMPARATOR

Atrasentan placebo group

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mosleh UDDIN, PharmD

Role: STUDY_DIRECTOR

Abbott Japan Co.,Ltd

Locations

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

Kōriyama, , 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, , 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, , Japan

Countries

Japan

References

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.

Reference Type: RESULT

PMID: 24722445 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26153128 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28756065 (View on PubMed)

Other Identifiers

M12-812

Identifier Type: -

Identifier Source: org_study_id