Atrasentan Spermatogenesis and Testicular Function

Inclusion Criteria:

- Males 30 to 75 years of age

- Type 1 or 2 diabetes and receiving treatment with at least one anti-hyperglycemic
medication and angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor
blockers (ARB) (renin-angiotensin system [RAS] inhibitor)

- Estimated Glomerular Filtration Rate (eGFR) equal to or greater than 35 mL/min with
the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Formula and Urine
Albumin-to-Creatinine Ratio (UACR) equal to or greater than 30 and less than 5,000
mg/g creatinine.

- Able to provide a semen specimen at the required intervals.

- Baseline sperm concentration equal to or greater than 30 million per mL.

Exclusion Criteria:

- Treatment with hormone suppressive agents or cancer chemotherapy within the past 6
months or planned during the study.

- History of severe peripheral edema or facial edema unrelated to trauma or history of
myxedema in the prior 4 weeks prior to screening.

- History of pulmonary hypertension, pulmonary fibrosis or any lung disease requiring
oxygen therapy.

- Documented diagnosis of heart failure, previous hospitalization for heart failure or
current or constellation of symptoms (dyspnea on exertion, pedal edema, orthopnea,
paroxysmal nocturnal dyspnea) felt to be compatible with heart failure, that was not
explained by other causes, and for which there was a change in medication or other
management directed at heart failure.

- Currently receiving or has received hormone replacement therapy within 6 months prior
to screening.