Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan

NCT01424319 | Completed Phase 2 DMC

• 1 other identifier: M12-812
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 18

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

Keywords

Endothelin Receptor Antagonists; Proteinuria

Outcome Measures

Primary Outcomes (1)

• The change from baseline to each post-baseline visit in log-transformed UACR (urinary albumin to creatinine ratio)

  Up to Week 12

Secondary Outcomes (3)

• 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

Study Arms (3)

ABT-627, Low dose

EXPERIMENTAL

Drug: Atrasentan low dose group

ABT-627, High dose

EXPERIMENTAL

Drug: Atrasentan high dose group

ABT-627, Placebo

PLACEBO COMPARATOR

Drug: Atrasentan placebo group

Interventions

Atrasentan low dose group 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, Low dose

Atrasentan high dose group 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

Atrasentan placebo group 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

Eligibility Criteria

• Age: 20 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (18)

Site Reference ID/Investigator# 62022

Azumino, Japan

Location

Site Reference ID/Investigator# 58124

Chiba, Japan

Location

Site Reference ID/Investigator# 57486

Fujisawa, Japan

Location

Site Reference ID/Investigator# 55097

Ibaraki, Japan

Location

Site Reference ID/Investigator# 56982

Ina, Japan

Location

Site Reference ID/Investigator# 55093

Kawagoe, Japan

Location

Site Reference ID/Investigator# 57485

Kawasaki, Japan

Location

Site Reference ID/Investigator# 55092

Kōriyama, Japan

Location

Site Reference ID/Investigator# 56524

Matsumoto, Japan

Location

Site Reference ID/Investigator# 57242

Nagano, Japan

Location

Site Reference ID/Investigator# 55781

Nagoya, Japan

Location

Site Reference ID/Investigator# 60965

Nagoya, Japan

Location

Site Reference ID/Investigator# 55304

Suwa, Japan

Location

Site Reference ID/Investigator# 59474

Tokyo, Japan

Location

Site Reference ID/Investigator# 59967

Ueda, Japan

Location

Site Reference ID/Investigator# 55095

Yokohama, Japan

Location

Site Reference ID/Investigator# 57484

Yokohama, Japan

Location

Site Reference ID/Investigator# 59842

Yokohama, Japan

Location

Related Publications (3)

• 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.

  PMID: 24722445 RESULT

• 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.

  PMID: 26153128 RESULT

• 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.

  PMID: 28756065 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Diabetic Nephropathies; Proteinuria

Interventions

Atrasentan; Population Groups

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodioxoles; Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrrolidines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Demography; Population Characteristics

Study Officials

• Mosleh UDDIN, PharmD

  Abbott Japan Co.,Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2011
• First Posted: August 29, 2011
• Study Start: August 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: August 29, 2017

Record last verified: 2017-08

Locations

JP (18)