Study Of Diabetic Nephropathy With Atrasentan

Inclusion Criteria:

• Participant, or legal representative, had voluntarily signed and dated an InformedConsent Form, approved by an Institutional Review Board (IRB)/Independent EthicsCommittee (IEC), after the nature of the study had been explained and the participanthad the opportunity to ask questions. The informed consent must have been signedbefore any study-specific procedures were performed.

• Participant had type 2 diabetes (including participants with latent autoimmunediabetes or insulin-treated participants without a history of diabetic ketoacidosiswho also had a negative anti-glutamic acid decarboxylase test AND an elevatedpost-prandial serum C-peptide level) and had been treated with at least oneanti-hyperglycemic medication and an angiotensin-converting enzyme inhibitor (ACEi) orAngiotensin II receptor blocker (ARB; RAS inhibitor) for at least 4 weeks prior to theScreening S2 visit.

• For entry into the Run-In Period the participant must have satisfied the followingcriteria based on the Screening laboratory values:

• Estimated glomerular filtration rate (eGFR) 25 to 75 mL/min/1.73 m^2 [until theeGFR cap on participants (approximately 300) with a baseline of > 60 mL/min/1.73m^2 was reached] and a urine albumin creatinine ratio (UACR) greater than orequal to 300 and less than 5,000 mg/g (greater than or equal to 34 mg/mmol andless than 565 mg/mmol);

• Serum albumin greater than or equal to 2.5 g/dL (25 g/L);

• Brain natriuretic peptide (BNP) less than or equal to 200 pg/mL (200 ng/L);

• Systolic blood pressure (SBP) greater than or equal to 110 and less than or equalto 180 mmHg;

• Serum potassium greater than or equal to 3.5 mEq/L (3.5 mmol/L) and less than orequal to 6.0 mEq/L (6.0 mmol/L);

• Participants on a maximum tolerated labeled daily dose (MTLDD) of a RAS inhibitorfor greater than or equal to 4 weeks and on a diuretic at the time of screeningand who satisfied the above criteria may have proceeded to the last visit in theRun-In Period (R6);

• Participants already on a MTLDD of a RAS inhibitor for greater than or equal to 4weeks and not on a diuretic (unless medically contraindicated) at the time ofScreening were to start with a diuretic and participate in Run-In for at least 2weeks.

• For entry into the Enrichment Period the participant must have satisfied the followingcriteria based on the last visit of the Run-In Period:

• RAS inhibitor at the MTLDD for the previous 4 weeks with no adjustments of thedose;

• Participants that were on a MTLDD RAS inhibitor and not on a diuretic (unlessmedically contraindicated) at the time of Screening must have been in Run-In forat least 2 weeks.

• For entry into the Double-Blind Treatment Period, participants must have satisfied thefollowing criteria based on the last visit of the Enrichment Period:

• RAS inhibitor at the MTLDD for the previous 6 weeks during the Enrichment Periodwith no adjustments of the dose;

• Diuretic at any dose unless medically contraindicated or clinically intolerablein the investigator's judgement (i.e., hypotension or hypokalemia);

• Participants must not have had a weight change greater than or equal to 3 kg fromthe beginning of Enrichment to the end of the Enrichment Period and absoluteserum BNP greater than or equal to 300 pg/mL (300 ng/L) at the last Enrichmentvisit;

• Participants must not have had an increase in serum creatinine greater than 0.5mg/dL and greater than 20% increase from the beginning of Enrichment to the endof the Enrichment Period.

Exclusion Criteria: A participant was not eligible for entry into the Run-in Period if he/she met any of thefollowing criteria:

• Participant had a history of severe peripheral edema or facial edema requiringdiuretics unrelated to trauma or a history of myxedema in the prior 4 weeks to theinitial Screening S1 visit.

• Participant had a history of pulmonary hypertension, pulmonary fibrosis or any lungdiseases requiring oxygen therapy (e.g., chronic obstructive pulmonary disease,emphysema).

• Participant had a documented diagnosis of heart failure, previous hospitalization forheart failure or current or constellation of symptoms (dyspnea on exertion, pedaledema, orthopnea, paroxysmal nocturnal dyspnea) felt to be compatible with heartfailure, that was not explained by other causes, and for which there was a change inmedication or other management directed at heart failure.

• Participant had known non-diabetic kidney disease (other than kidney stones).

• Participant had elevated liver enzymes (serum alanine aminotransaminase [ALT] and/orserum aspartate aminotransaminase [AST]) > 3 × the upper limit of normal (ULN).

• Participant had hemoglobin < 9 g/dL (90 g/L).

• Participant had a sensitivity to loop diuretics.

• Participant had a history of an allergic reaction or significant sensitivity toatrasentan (or its excipients) or similar compounds.

• Participant had a history of chronic gastrointestinal disease, which, in theInvestigator's opinion, may have caused significant GI malabsorption.

• Participant had a history of secondary hypertension (i.e., hemodynamically significantrenal artery stenosis, primary aldosteronism or pheochromocytoma).

• Participant had significant comorbidities (e.g., advanced malignancy, advanced liverdisease) with a life expectancy of less than 1 year.

• Participant had clinically significant cerebrovascular disease (CVD) or coronaryartery disease (CAD) within 3 months prior to the Screening S1 visit, defined as oneof the following:

• Hospitalization for MI or unstable angina; or

• New onset angina with positive functional study or coronary angiogram revealingstenosis; or

• Coronary revascularization procedure; or

• Transient Ischemic Attack or Stroke.

• Participant had received any investigational drug including atrasentan within 3 monthsprior to the Screening S1 visit.

• Participant received dialysis treatments or was expected to receive dialysis or renaltransplant within 6 months of screening.

• Participant was currently receiving rosiglitazone, moxonidine, aldosterone blockers,aliskiren or a combination of ACEi and ARB.

• Participant was a premenopausal woman defined as (for study purposes) any femalesubject with a menses in the past 2 years. For women who were < 50 years old, serumFSH must have been greater than 35 IU/L. Women who were surgically sterile or had ahistory of hysterectomy may not have necessarily be postmenopausal, and must also havehad an FSH > 35 IU/L.

• Participant was at high risk for QT/QTc prolongation such as a family history of LongQT Syndrome, defined as QTc prolongation exceeding 450 ms in men, or 460 ms in women.

• Participant had type 1 diabetes.

• Participant was considered to be clinically unstable regarding general, metabolic orcardiovascular health as determined by the Investigator.