Atrasentan Spermatogenesis and Testicular Function

Study Overview
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Brief Summary
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This study is being conducted to evaluate the effects of Atrasentan on sperm production and testicular function in male subjects with Type 1 or 2 Diabetes and Nephropathy. This study included 2 periods: a Treatment Period (up to 26 weeks) followed by an Observational Period (up to an additional 52 weeks).

Official Title
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A Multicenter, Single-Arm Study of the Effects of Atrasentan on Spermatogenesis and Testicular Function

Conditions
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Nephropathy, Diabetes

Intervention / Treatment
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* Drug: Atrasentan


Participation Criteria
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Eligibility Criteria
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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/1.73 m^2 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 6 months prior to the initial screening visit 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.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atrasentan<br>Atrasentan 0.75 mg administered orally once daily (QD) for 26 weeks | Drug: Atrasentan<br>* Atrasentan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With a Sperm Concentration < 15 Million Per mL by Treatment Week 26 | Percentage of Subjects with a Sperm Concentration < 15 million per mL by Treatment Week 26. Sperm concentration was calculated as measure of the number sperm per milliliter of semen. Duplicate semen samples were collected. The average of the 2 samples were used as the value for that scheduled collection period. | Up to 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Entered the Observation Period and Did Not Return to Within 15% of Baseline Sperm Concentration or Above During the 52-Week Observational Period | The percentage of participants who entered the Observational Period and did not return to within 15% of Baseline sperm concentration or above during the 52-week Observational Period. Duplicate semen samples were to be collected during the Observational Period. Sperm concentration was calculated as measure of the number sperm per milliliter of semen. Duplicate semen samples were collected. The average of the 2 samples were used as the value for that scheduled collection period. | Up to 52 weeks after the Treatment Period | 
| Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Sperm Concentration | Duplicate semen samples will be collected during the Treatment and Observational Periods. The average of the 2 samples were used as the value for that scheduled collection period. A negative change from baseline indicated a decrease in sperm concentration. | From Week 0 up to Treatment Period Week 26 and Observation Period Week 52 | 
| Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Sperm Motility | Duplicate semen samples will be collected during the Treatment and Observation Periods. The average of the 2 samples were used as the value for that scheduled collection period. A negative change from baseline indicated a lower sperm motility (worsening). | From Week 0 up to Treatment Period Week 26 and Observation Observation Week 52 | 
| Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Sperm Morphology | Duplicate semen samples will be collected during the Treatment and Observational Periods. The percentage of sperm with normal versus abnormal morphology will be determined via microscopic analysis. A positive change from baseline indicates an improved sperm morphology. | From Week 0 up to Treatment Period Week 26 and Observation Period Week 52 | 
| Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Semen Volume | Duplicate semen samples will be collected during the Treatment and Observation Periods. The average of the 2 samples were used as the value for that scheduled collection period. A negative change from baseline indicated a decrease in semen volume. | From Week 0 to up to Treatment Period Week 26 and Observation Period Week 52 | 
| Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Serum Testosterone | Serum hormones levels will be tested during the Treatment and Observational Periods. A negative change from baseline indicated a decrease in serum testosterone. | From Week 0 up to Treatment Period Week 26 and Observation Period Week 52 | 
| Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Estradiol | Serum hormones levels were tested during the Treatment and Observational Periods. A negative change from baseline indicated a decrease in serum estradiol. | From Week 0 up to Treatment Period Week 26 and Observation Period Week 52 | 
| Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Lutenizing Hormone (LH) | Serum hormones levels will be tested during the Treatment and Observational Periods. A positive change from baseline indicated an increase in serum lutenizing hormone. | From Week 0 to up to Treatment Period Week 26 and Observation Period Week 52 | 
| Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in in Follicle Stimulating Hormone (FSH) | Serum hormones levels will be tested during the Treatment and Observational Periods. A positive change from baseline indicated an increase in serum follicle stimulating hormone. | From Week 0 to Treatment Week 26 and Observation Week 52 | 
| Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Inhibin B | Serum hormones levels will be tested during the Treatment and Observational Periods. A negative change from baseline indicated a decrease in serum Inhibin B. | From Week 0 up to Treatment Period Week 26 and Observation Period Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Nephropathies, Kidney Diseases, Urologic Diseases, Diabetes Complications, Diabetes Mellitus, Endocrine System Diseases