The Effect of Tracleer® on Male Fertility

TRACLEER® (Bosentan) Pulmonary Arterial Hypertension A Multicenter, Open-label, Single-arm Safety Study to Investigate the Effects of Chronic TRACLEER® Treatment on Testicular Function in Male Patients With Pulmonary Arterial Hypertension

The objective of the study is to evaluate the effects of chronic TRACLEER® treatment on testicular function via semen analysis in male patients with primary pulmonary arterial hypertension (PAH).

Study Overview

• Status: Completed
• Conditions: Hypertension, Pulmonary
• Intervention / Treatment: Drug: bosentan

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Darlinghurst, Australia, 2010
    • St. Vincent's Hospital
  • Perth, Australia, 6000
    • Royal Perth Hospital
• Brazil
  • Sao Paulo, Brazil
    • University of Sao Paulo
  • Sao Paulo, Brazil
    • Federal University of São Paulo
• Czech Republic
  • Brno, Czech Republic
    • 1st Internal Cardiology Clinic
  • Prague, Czech Republic
    • The Center for Congenital Heart Disease in Adults
• Hungary
  • Budapest, Hungary, 1529
    • National Korányi Institute of Pulmonology
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama-Birmingham
  • California
    • La Jolla, California, United States, 92037-1300
      • University of California at San Diego
    • Torrance, California, United States, 90502
      • Harbor - UCLA Medical Center
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Health Sciences Center
  • New York
    • New York, New York, United States, 10032-3784
      • New York Presbyterian Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male patients age 18-65 years.
• Bosentan-naïve.
• PPH, WHO functional class III/IV, in need of TRACLEER
• Patients pulmonary arterial hypertension (PAH) secondary to congenital heart disease.
• Written informed consent.

Exclusion Criteria:

• Female
• Patients with PAH secondary to connective tissue vascular diseases or HIV.
• Patients who have undergone a vasectomy.
• Patients with an average baseline sperm concentration < 15 x 10[6]/mL, or any sample with a sperm concentration <= 7.5 x 10[6]/mL.
• Patients with an average baseline sperm motility <20% or normal sperm morphology <5%.
• Body weight < 50 kg.
• Hypotension, defined as systolic blood pressure less than 85 mm Hg.
• AST and/or ALT plasma levels greater than 3 times ULN.
• Hypersensitivity to bosentan or any of the components of the formulation.
• Treatment with glyburide, cyclosporine A or tacrolimus at inclusion or planned during the study.
• Treatment with hormone suppressive agents, including androgens, estrogens, anabolic steroids or glucocorticoids within the past 6 months or planned during the study.
• Current treatment less than 3 months prior to inclusion or planned treatment with prostacyclin or prostacyclin analogues (e.g., Flolanâ or Remodulin).
• Patients who received an investigational drug in the month preceding the study start or who are due to be treated with another investigational drug during the study period.
• Known drug or alcohol dependence or any other factors that will interfere with conduct of the study.
• Any illness other than PPH that will reduce life expectancy to less than 6 months.
• Active cancer.
• Prior treatment with an anti-neoplastic agent or ionizing radiation.
• Hot tub/Jacuzzi use.
• Uncontrolled diseases including diabetes, liver or kidney disease.
• Patients receiving spironolactone (aldactone) less than 3 months prior to inclusion or dose >25 mg/day at baseline or anytime during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Oral bosentan tablets	Drug: bosentan; Oral bosentan tablets 62.5 mg twice daly for 4 weeks, then 125 mg twice daily for 20 weeks.; Other Names: Tracleer (R)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with a mean decrease in sperm concentration to 7.5 x 10[6]/mL or below, without a single sperm concentration ≥ 20 x 10[6]/mL, at 3 or 6 months. This proportion is considered of clinical relevance if greater than 30%.	From baseline to end of study.

Secondary Outcome Measures

Outcome Measure	Time Frame
Semen volume, sperm motility and sperm morphology change	From baseline to 3 & 6 months

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Andrea Lauer, Ph.D., Actelion Pharmaceuticals US, Inc.; Study Director: Maurizio Rainisio, Ph.D., Actelion; Study Director: Frederic Bodin, M.D., Actelion

Publications and helpful links

Helpful Links

• Tracleer approval page at Drugs@FDA.gov

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: April 30, 2004
• First Submitted That Met QC Criteria: May 3, 2004
• First Posted (Estimated): May 4, 2004

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 31, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; Bosentan
• Other Study ID Numbers: AC-052-402