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

NCT ID: NCT00920764

Last Updated: 2018-06-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

92 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-06-30

Study Completion Date

2010-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Kidney Disease Diabetic Nephropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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A

Group Type ACTIVE_COMPARATOR

1.75 mg Atrasentan QD

Intervention Type DRUG

10 mL oral solution, daily, 8 weeks

B

Group Type ACTIVE_COMPARATOR

0.25 mg Atrasentan QD

Intervention Type DRUG

10 mL oral solution, daily, 8 weeks

C

Group Type ACTIVE_COMPARATOR

0.75 mg Atrasentan QD

Intervention Type DRUG

10 mL oral solution, daily, 8 weeks

D

Group Type PLACEBO_COMPARATOR

Placebo for Atrasentan 0.2 mg/mL solution

Intervention Type DRUG

10 mL oral solution, daily, 8 weeks

Interventions

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Placebo for Atrasentan 0.2 mg/mL solution

10 mL oral solution, daily, 8 weeks

Intervention Type DRUG

0.25 mg Atrasentan QD

10 mL oral solution, daily, 8 weeks

Intervention Type DRUG

0.75 mg Atrasentan QD

10 mL oral solution, daily, 8 weeks

Intervention Type DRUG

1.75 mg Atrasentan QD

10 mL oral solution, daily, 8 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 1.Subject is \>= 18 years old.
* 2.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.
* 3.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.
* 4.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.
* 5.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.
* 6.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.
* 7.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.

Exclusion Criteria

* 1.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.
* 2.Subject receiving loop diuretics \> 30 mg BID of furosemide or \> 0.5 mg BID of bumetanide or \> 25 mg BID of ethacrynic acid.
* 3.Subject has a history of pulmonary edema.
* 4.Subject has a history of pulmonary hypertension, chronic obstructive pulmonary disease, emphysema, pulmonary fibrous disease, asthma or other lung disease that requires oxygen.
* 5.Subject has a documented history of heart failure, defined as New York Heart Association (NYHA) Class II, III or IV heart failure.
* 6.Subject has a body mass index (BMI) \> 40.
* 7.Subject has elevated liver enzymes (ALT and/or AST) \> 1.5 x the upper limit of normal (ULN).
* 8.Subject has a hemoglobin \< 9.5 g/dL.
* 9.Subject has a history of an allergic reaction or significant sensitivity to atrasentan or its excipients.
* 10.Subject has a history of a chronic gastrointestinal disease, which in the Investigator's opinion may cause significant GI malabsorption.
* 11.Subject has a history of secondary hypertension (i.e., renal artery stenosis, primary aldosteronism or pheochromocytoma).
* 12.Subject has poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg and or diastolic blood pressure ≥ 90 mmHg) or hypotension (systolic blood pressure \<= 90 mmHg).
* 13.Subject has significant comorbidities (e.g., advanced malignancy, advanced liver disease) with a life expectancy less than 1 year.
* 14.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.
* 15.Subject has clinically significant coronary artery disease (CAD) within 3 months prior to the Screening Period, defined as one of the following:

* Hospitalization for MI or unstable angina; or
* New onset angina with positive functional study or coronary angiogram revealing stenosis; or
* Coronary revascularization procedure.
* 16.Subject has a history of viral or bacterial infection within 4 weeks of Screening or HIV infection.
* 17.Subject has scheduled or planned surgery with general anesthesia within 12 weeks of Screening Visit.
* 18.Subject has a history of drug or alcohol abuse within 6 months prior to the Screening Visit.
* 19.Subject has evidence of poor compliance with diet or medication that may interfere, in the Investigator's opinion, with adherence to the protocol.
* 20.Subject has received any investigational drug within 30 days prior to study drug administration.
* 21.For any reason, subject is considered by the Investigator to be an unsuitable candidate to receive atrasentan oral solution or is put at risk by study procedures
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dennis Andress

Role: STUDY_DIRECTOR

AbbVie

Locations

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Site Reference ID/Investigator# 19386

Tempe, Arizona, United States

Site Status

Site Reference ID/Investigator# 25043

Azusa, California, United States

Site Status

Site Reference ID/Investigator# 23308

Los Angeles, California, United States

Site Status

Site Reference ID/Investigator# 25430

Los Angeles, California, United States

Site Status

Site Reference ID/Investigator# 20421

San Diego, California, United States

Site Status

Site Reference ID/Investigator# 22442

San Diego, California, United States

Site Status

Site Reference ID/Investigator# 21061

Whittier, California, United States

Site Status

Site Reference ID/Investigator# 16572

Yuba City, California, United States

Site Status

Site Reference ID/Investigator# 26142

Coral Gables, Florida, United States

Site Status

Site Reference ID/Investigator# 16567

Hudson, Florida, United States

Site Status

Site Reference ID/Investigator# 16577

Pembroke Pines, Florida, United States

Site Status

Site Reference ID/Investigator# 25242

Pembroke Pines, Florida, United States

Site Status

Site Reference ID/Investigator# 16569

Rockville, Maryland, United States

Site Status

Site Reference ID/Investigator# 16574

Omaha, Nebraska, United States

Site Status

Site Reference ID/Investigator# 20221

Buffalo, New York, United States

Site Status

Site Reference ID/Investigator# 16576

Greenville, North Carolina, United States

Site Status

Site Reference ID/Investigator# 16573

Morehead City, North Carolina, United States

Site Status

Site Reference ID/Investigator# 26143

Statesville, North Carolina, United States

Site Status

Site Reference ID/Investigator# 19383

Bethlehem, Pennsylvania, United States

Site Status

Site Reference ID/Investigator# 26365

Orangeburg, South Carolina, United States

Site Status

Site Reference ID/Investigator# 16571

San Antonio, Texas, United States

Site Status

Site Reference ID/Investigator# 16566

San Antonio, Texas, United States

Site Status

Site Reference ID/Investigator# 19384

San Antonio, Texas, United States

Site Status

Site Reference ID/Investigator# 24542

Fairfax, Virginia, United States

Site Status

Site Reference ID/Investigator# 16564

Las Piedras, , Puerto Rico

Site Status

Site Reference ID/Investigator# 19381

Ponce, , Puerto Rico

Site Status

Site Reference ID/Investigator# 16563

San Juan, , Puerto Rico

Site Status

Site Reference ID/Investigator# 16562

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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.

Reference Type BACKGROUND
PMID: 26239562 (View on PubMed)

Other Identifiers

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M10-815

Identifier Type: -

Identifier Source: org_study_id

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