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 is an interventional treatment trial for Chronic Kidney Disease focused on measuring Endothelin Receptor Antagonists, Proteinuria Read More

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.