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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT00920764
First received: June 11, 2009
Last updated: March 26, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Chronic Kidney Disease
Diabetic Nephropathy
Drug: Placebo for Atrasentan 0.2 mg/mL solution
Drug: 0.25 mg Atrasentan QD
Drug: 0.75 mg Atrasentan QD
Drug: 1.75 mg Atrasentan QD
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2a, Prospective, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Safety and Efficacy of Atrasentan on Reducing Albuminuria in Type 2 Diabetic Nephropathy Subjects Who Are Currently Being Treated With an Renin-Angiotensin System Inhibitor

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Mean change from baseline to each post-baseline observation on UACR over the course of treatment period versus standard of care [ Time Frame: Week 8 visit or final assessment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects achieving at least a 25% reduction in final UACR levels from baseline [ Time Frame: Week 8 visit or final assessment ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving at least a 40% reduction in final UACR levels from baseline [ Time Frame: Week 8 visit or final assessment ] [ Designated as safety issue: No ]
  • Change from baseline to the final value in UACR, estimated glomerular filtration rate (eGFR), Neutrophil Gelatinase-Associated Lipocalin (NGAL) [ Time Frame: Week 8 visit or final assessment ] [ Designated as safety issue: No ]
  • Change from baseline to each weekly measurement in NGAL [ Time Frame: Week 8 visit or final assessment ] [ Designated as safety issue: No ]

Enrollment: 92
Study Start Date: June 2009
Study Completion Date: May 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A Drug: 1.75 mg Atrasentan QD
10 mL oral solution, daily, 8 weeks
Active Comparator: B Drug: 0.25 mg Atrasentan QD
10 mL oral solution, daily, 8 weeks
Active Comparator: C Drug: 0.75 mg Atrasentan QD
10 mL oral solution, daily, 8 weeks
Placebo Comparator: D Drug: Placebo for Atrasentan 0.2 mg/mL solution
10 mL oral solution, daily, 8 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00920764

  Show 28 Study Locations
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Dennis Andress AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT00920764     History of Changes
Other Study ID Numbers: M10-815
Study First Received: June 11, 2009
Last Updated: March 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by AbbVie:
CKD Stages 3&4
Endothelin antagonist
Proteinuria

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Diabetic Nephropathies
Albuminuria
Urologic Diseases
Renal Insufficiency
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Proteinuria
Urination Disorders
Urological Manifestations
Signs and Symptoms
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014