A Study of Atrasentan on Reducing Albuminuria in Type 2 Diabetic Nephropathy Treated With Renin-Angiotensin System Inhibitors

NCT00920764 | Completed Phase 2

• 1 other identifier: M10-815
• Study Type: interventional
• Target: 92
• Locations: 2 countries
• Sites: 28

Brief Summary

The study objective is to investigate the effects of three low doses of atrasentan on urinary albumin/creatinine ratio (UACR) levels in subjects with Type 2 diabetic nephropathy. Patients with Type 2 diabetes with nephropathy must be receiving a renin-angiotensin system inhibitor, such as an Angiotensin converting enzyme inhibitor (ACEi) or an Angiotensin II Receptor Blocker (ARB) for participation in this study. ACEi and ARB treatment are the standard of care for the management of proteinuria in Chronic Kidney Disease (CKD) patients.

Conditions

Chronic Kidney Disease; Diabetic Nephropathy

Keywords

CKD Stages 3&4; Endothelin antagonist; Proteinuria

Outcome Measures

Primary Outcomes (1)

• Mean change from baseline to each post-baseline observation on UACR over the course of treatment period versus standard of care

  Week 8 visit or final assessment

Secondary Outcomes (4)

• Proportion of subjects achieving at least a 25% reduction in final UACR levels from baseline

  Week 8 visit or final assessment

• Proportion of subjects achieving at least a 40% reduction in final UACR levels from baseline

  Week 8 visit or final assessment

• Change from baseline to the final value in UACR, estimated glomerular filtration rate (eGFR), Neutrophil Gelatinase-Associated Lipocalin (NGAL)

  Week 8 visit or final assessment

• Change from baseline to each weekly measurement in NGAL

  Week 8 visit or final assessment

Study Arms (4)

A

ACTIVE COMPARATOR

Drug: 1.75 mg Atrasentan QD

B

ACTIVE COMPARATOR

Drug: 0.25 mg Atrasentan QD

C

ACTIVE COMPARATOR

Drug: 0.75 mg Atrasentan QD

D

PLACEBO COMPARATOR

Drug: Placebo for Atrasentan 0.2 mg/mL solution

Interventions

Placebo for Atrasentan 0.2 mg/mL solution DRUG

10 mL oral solution, daily, 8 weeks

D

0.25 mg Atrasentan QD DRUG

10 mL oral solution, daily, 8 weeks

B

0.75 mg Atrasentan QD DRUG

10 mL oral solution, daily, 8 weeks

C

1.75 mg Atrasentan QD DRUG

10 mL oral solution, daily, 8 weeks

A

Eligibility Criteria

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

You may qualify if:

• Subject is \>= 18 years old.
• Subject has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject has had the opportunity to ask questions. The informed consent must be signed before any study-specific procedures are performed.
• Subject has Type 2 diabetes and has been treated with at least one anti-hyperglycemic medication within the 12 months prior to the Screening Phase.
• Subject has been receiving a stable dose (i.e., same type and regimen) of angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blocking agents (ARB) for at least 2 months prior to the Screening Phase.
• If female, subject must be not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy). The reason for non-childbearing potential must be specified in the subject's eCRF.
• If male, subject must be surgically sterile or if sexually active and of childbearing potential, the site must document the lack of desire for future procreation and subject must agree to use a condom and a second reliable barrier of contraception from the Screening Visit through two months following completion of their participation in the study.
• For entry into the Treatment Phase the subject must satisfy the following criteria based on Screening laboratory values:
• a.Estimated GFR \> 20 mL/min/1.73 m2 by simplified MDRD formula
• b.UACR between 100 and 3000 mg/g as determined at the initial Screening visit or by the mean of the 2 morning void urine specimens obtained prior to the second Screening visit.
• c.Serum albumin \> 3.0 g/dL.
• d.HbA1c \<= 10%.
• e.Pro-BNP \<= 500pg/mL.
• f.Negative urine pregnancy test for female subjects.

You may not qualify if:

• Subject has a history of significant peripheral edema (2 + or greater), or facial edema unrelated to trauma, or a history of myxedema in the 6 months prior to Screening.
• Subject receiving loop diuretics \> 30 mg BID of furosemide or \> 0.5 mg BID of bumetanide or \> 25 mg BID of ethacrynic acid.
• Subject has a history of pulmonary edema.
• Subject has a history of pulmonary hypertension, chronic obstructive pulmonary disease, emphysema, pulmonary fibrous disease, asthma or other lung disease that requires oxygen.
• Subject has a documented history of heart failure, defined as New York Heart Association (NYHA) Class II, III or IV heart failure.
• Subject has a body mass index (BMI) \> 40.
• Subject has elevated liver enzymes (ALT and/or AST) \> 1.5 x the upper limit of normal (ULN).
• Subject has a hemoglobin \< 9.5 g/dL.
• Subject has a history of an allergic reaction or significant sensitivity to atrasentan or its excipients.
• Subject has a history of a chronic gastrointestinal disease, which in the Investigator's opinion may cause significant GI malabsorption.
• Subject has a history of secondary hypertension (i.e., renal artery stenosis, primary aldosteronism or pheochromocytoma).
• Subject has poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg and or diastolic blood pressure ≥ 90 mmHg) or hypotension (systolic blood pressure \<= 90 mmHg).
• Subject has significant comorbidities (e.g., advanced malignancy, advanced liver disease) with a life expectancy less than 1 year.
• Subject is expected to receive an increased dose of current RAAS inhibitor (ACEi, ARB, renin or aldosterone inhibitor) during the course of the study. Conversions from one product to another (e.g., ACEi to ARB) must be at equivalent doses.
• Subject has clinically significant coronary artery disease (CAD) within 3 months prior to the Screening Period, defined as one of the following:

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (28)

Site Reference ID/Investigator# 19386

Tempe, Arizona, 85284, United States

Location

Site Reference ID/Investigator# 25043

Azusa, California, 91702, United States

Location

Site Reference ID/Investigator# 23308

Los Angeles, California, 90022, United States

Location

Site Reference ID/Investigator# 25430

Los Angeles, California, 90048, United States

Location

Site Reference ID/Investigator# 20421

San Diego, California, 92123, United States

Location

Site Reference ID/Investigator# 22442

San Diego, California, 92123, United States

Location

Site Reference ID/Investigator# 21061

Whittier, California, 90603, United States

Location

Site Reference ID/Investigator# 16572

Yuba City, California, 95991, United States

Location

Site Reference ID/Investigator# 26142

Coral Gables, Florida, 33134, United States

Location

Site Reference ID/Investigator# 16567

Hudson, Florida, 34667, United States

Location

Site Reference ID/Investigator# 16577

Pembroke Pines, Florida, 33028, United States

Location

Site Reference ID/Investigator# 25242

Pembroke Pines, Florida, 33028, United States

Location

Site Reference ID/Investigator# 16569

Rockville, Maryland, 20852, United States

Location

Site Reference ID/Investigator# 16574

Omaha, Nebraska, 68131, United States

Location

Site Reference ID/Investigator# 20221

Buffalo, New York, 14215, United States

Location

Site Reference ID/Investigator# 16576

Greenville, North Carolina, 27834, United States

Location

Site Reference ID/Investigator# 16573

Morehead City, North Carolina, 28557, United States

Location

Site Reference ID/Investigator# 26143

Statesville, North Carolina, 28625, United States

Location

Site Reference ID/Investigator# 19383

Bethlehem, Pennsylvania, 18017, United States

Location

Site Reference ID/Investigator# 26365

Orangeburg, South Carolina, 29115, United States

Location

Site Reference ID/Investigator# 16571

San Antonio, Texas, 78229-4801, United States

Location

Site Reference ID/Investigator# 16566

San Antonio, Texas, 78229, United States

Location

Site Reference ID/Investigator# 19384

San Antonio, Texas, 78229, United States

Location

Site Reference ID/Investigator# 24542

Fairfax, Virginia, 22030, United States

Location

Site Reference ID/Investigator# 16564

Las Piedras, 00771, Puerto Rico

Location

Site Reference ID/Investigator# 19381

Ponce, 00717, Puerto Rico

Location

Site Reference ID/Investigator# 16563

San Juan, 00918, Puerto Rico

Location

Site Reference ID/Investigator# 16562

San Juan, 00936-5067, Puerto Rico

Location

Related Publications (1)

• Perez-Gomez MV, Sanchez-Nino MD, Sanz AB, Martin-Cleary C, Ruiz-Ortega M, Egido J, Navarro-Gonzalez JF, Ortiz A, Fernandez-Fernandez B. Horizon 2020 in Diabetic Kidney Disease: The Clinical Trial Pipeline for Add-On Therapies on Top of Renin Angiotensin System Blockade. J Clin Med. 2015 Jun 18;4(6):1325-47. doi: 10.3390/jcm4061325.

  PMID: 26239562 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Diabetic Nephropathies; Proteinuria

Interventions

Atrasentan; Solutions

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; Pharmaceutical Preparations

Study Officials

• Dennis Andress

  AbbVie

  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: June 11, 2009
• First Posted: June 15, 2009
• Study Start: June 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: May 1, 2010
• Last Updated: June 6, 2018

Record last verified: 2013-01

Locations

US (24); PR (4)