Evaluate the Efficacy and Safety of Once Daily Administration of Atrasentan Tablets (Low and High) Compared to Placebo in Reducing Residual Albuminuria in Type 2 Diabetic Patients With Nephropathy Who Are Treated With the Maximum Tolerated Labeled Dose of a Renin Angiotensin System (RAS) Inhibitor (RADAR)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01356849
First received: April 19, 2011
Last updated: August 20, 2013
Last verified: August 2013
  Purpose

Prospective, Randomized, Double-Blind, Placebo-Controlled Multicenter Study. The objective of the study is to evaluate the efficacy and safety of once daily administration of atrasentan tablets (low dose and high dose) compared to placebo in reducing residual albuminuria in Type 2 diabetic patients with nephropathy who are treated with the maximum tolerated labeled dose of a Renin Angiotensin System (RAS) inhibitor. If the patient is already receiving a maximum tolerated labeled daily dose of RAS inhibitor and a diuretic, he/she will complete 4 weeks of the Run-in Period on a dose that has not been adjusted. If the patient is currently not receiving a maximum labeled daily dose of a RAS inhibitor then the dose will be titrated up to the maximum tolerated labeled dose over the course of 4 to 8 weeks during the Run-in Period. It is expected that subjects not receiving a diuretic will have a diuretic added or titrated during this period to maximize RAS inhibition. Following titration to the maximum tolerated labeled dose, the patient will complete an additional 4 weeks of Run-In Period on an unchanged doses of RAS inhibitor and diuretics, unless medically contraindicated. The randomization will be stratified based on country where subjects are enrolled into the study, and the Week -1 Urinary Albumin to Creatinine Ratio (UACR) levels (< or = 1000 mg/g [113 mg/mmol], or > 1000 mg/g [113 mg/mmol]). Within each stratum, subjects will be randomly assigned in a 1:2:2 ratio to one of the following blinded treatment groups: Group A - Placebo once daily (QD) Group B - low dose atrasentan QD Group C - high dose atrasentan QD After the 12 weeks of study drug treatment, subjects will be followed up to 30 days.


Condition Intervention Phase
Chronic Kidney Disease
Diabetic Nephropathy
Drug: Atrasentan
Drug: Placebo
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: RADAR: Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan - A Phase 2b, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety and Efficacy

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Change from baseline to Week 12 in Urinary Albumin to Creatinine Ratio (UACR) [ Time Frame: Every two weeks for 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Differences in change from baseline to each post baseline measure for estimated glomerular filtration rate (eGFR) [ Time Frame: Every two weeks for 12 weeks ] [ Designated as safety issue: No ]
  • Differences in change from baseline to each post baseline measure for EQ-5D Index Score [ Time Frame: Once a month for 3 months ] [ Designated as safety issue: No ]
  • Differences in change from baseline to each post baseline measure for each of the Kidney Disease Quality of Life (KDQOL) Kidney Disease Targeted Scales [ Time Frame: Once a month for 3 months ] [ Designated as safety issue: No ]

Enrollment: 149
Study Start Date: April 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Group A - Placebo QD Drug: Placebo
Subjects will take two tablets daily of placebo QD for 12 weeks during the treatment period.
Active Comparator: Group B - Low dose Atrasentan QD Drug: Atrasentan
Subjects will take two tablets daily of either low dose Atrasentan QD or high dose Atrasentan QD for 12 weeks during the treatment period.
Other Name: ABT-627
Active Comparator: Group C - High dose Atrasentan QD Drug: Atrasentan
Subjects will take two tablets daily of either low dose Atrasentan QD or high dose Atrasentan QD for 12 weeks during the treatment period.
Other Name: ABT-627

  Eligibility

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

Inclusion Criteria:

  • Patient is > or = 18 years old.
  • 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 currently receiving an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin II receptor blocker (ARB) (Renin Angiotensin System (RAS) inhibitor).
  • For entry in the Run-in Period the patient must satisfy the following criteria based on the Screening laboratory values:

    • Estimated glomerular filtration rate (eGFR) ≥ 30 and ≤ 75 mL/min/1.73m2 by Epidemiology Collaboration (EPI) formula
    • Urinary Albumin to Creatinine Ratio (UACR) > or = 300 and < or = 3500 mg/g as determined by the geometric mean of the two morning void urine specimens obtained at the Screening visit (UACR > or = 34 mg/mmol and < or = 396 mg/mmol)
    • Serum albumin > or = 3.0 g/dL (30 g/L) - B-type Natriuretic Peptide (BNP) < or = 200 pg/mL (57.8 pmol/L) * Negative serum pregnancy test for female patients
    • Systolic Blood Pressure (SBP) > or = 110 mmHg and < or = 180 mmHg
    • Glucosylated hemoglobin A1c (HbA1c) < or = 12%
  • For entry in the Treatment Period the patient must satisfy the following criteria based on the last visit of the Run-in Period laboratory values:

    • Renin Angiotensin System (RAS) inhibitor at maximum tolerated labeled dose for the previous 4 weeks with no adjustments of dose
    • Diuretic at any dose unless medically contraindicated (with the exception of loop diuretics > or = 120 mg QD of furosemide or > or = 3.0 mg QD of bumetanide or > or = 150 mg QD of ethacrynic acid or > or = 60 mg QD of torasemide)
    • Urinary Albumin to Creatinine Ratio (UACR) > or = 200 and < or = 3500 mg/g as determined by the median of the three morning void urine specimens obtained prior to the Week -1 visit (UACR > or = 23 mg/mmol and < or = 396 mg/mmol)
    • Systolic blood pressure (SBP) > or = 110 mmHg and < or = 160 mmHg
    • Serum Potassium < or = 5.5 mEq/L (5.5 mmol/L)
    • Negative serum pregnancy test for female patients

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 > or = 120 mg QD of furosemide or > or = 3.0 mg QD of bumetanide or > or = 150 mg QD of ethacrynic acid or > or = 60 mg QD of torasemide.
  • Patient has a history of pulmonary edema.
  • Patient has a history of pulmonary hypertension, or any lung diseases requiring oxygen therapy (i.e., chronic obstructive pulmonary disease, emphysema, pulmonary fibrosis).
  • Patient has a history of orthostatic hypotension within the past 6 months as defined by the presence of a supine-to-standing blood pressure decrease > or = 20 mmHg systolic or > or = 10 mmHg diastolic within 3 minutes of standing.
  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: NCT01356849

  Show 72 Study Locations
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Blai Coll, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01356849     History of Changes
Other Study ID Numbers: M11-350
Study First Received: April 19, 2011
Last Updated: August 20, 2013
Health Authority: Taiwan: Department of Health
Canada: Health Canada
United States: Food and Drug Administration

Keywords provided by AbbVie:
Endothelin Receptor Antagonists
Proteinuria

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

ClinicalTrials.gov processed this record on October 22, 2014