Atrasentan Spermatogenesis and Testicular Function

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

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).

Study Overview

• Status: Completed
• Conditions: Diabetes; Nephropathy
• Intervention / Treatment: Drug: Atrasentan

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charite Research Organisation GmbH /ID# 154264
• Italy
  • Milan, Italy, 20153
    • Ospedale S. Carlo Borromeo /ID# 151672
  • Torino, Italy, 10154
    • SCDU Nefrologia e dialisi-CMID /ID# 151673
• Spain
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina S /ID# 151692
• United States
  • California
    • Laguna Hills, California, United States, 92653-3621
      • Alliance Research Centers /ID# 125945
    • Santa Monica, California, United States, 90404
      • Frank Clark Urology Center /ID# 147794
  • Illinois
    • Evergreen Park, Illinois, United States, 60805
      • Research by Design, LLC /ID# 160784
    • Springfield, Illinois, United States, 62702
      • Southern IL Univ School of Med /ID# 129010
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Crescent City Clinical Res Ctr /ID# 150989
    • New Orleans, Louisiana, United States, 70112
      • Tulane Univ /ID# 130308
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College /ID# 131068
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004-1017
      • Urologic Consultants of Southeastern Pennsylvania /ID# 124277
  • Virginia
    • Norfolk, Virginia, United States, 23507-1627
      • Eastern Virginia Med School /ID# 153740

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atrasentan; Atrasentan 0.75 mg administered orally once daily (QD) for 26 weeks	Drug: Atrasentan; Atrasentan

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2015
• Primary Completion (Actual): April 18, 2018
• Study Completion (Actual): July 16, 2018

Study Registration Dates

• First Submitted: April 14, 2014
• First Submitted That Met QC Criteria: April 17, 2014
• First Posted (Estimate): April 21, 2014

Study Record Updates

• Last Update Posted (Actual): May 7, 2019
• Last Update Submitted That Met QC Criteria: May 3, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Diabetes Complications; Urologic Diseases; Kidney Diseases; Diabetic Nephropathies; Endocrine System Diseases
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Endothelin Receptor Antagonists; Endothelin A Receptor Antagonists; Atrasentan
• Other Study ID Numbers: M12-919; 2016-000722-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No