BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology

A Multi-Center, Open-Label Extension Study to Protocol AC-052-405 to Evaluate the Safety and Efficacy of Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology

This 6-month open label study will evaluate the long term safety of bosentan (via oxygen saturation) and efficacy (exercise capacity) in patients who have completed the BREATHE-5 study (PAH related to Eisenmenger physiology). Treatment duration is 6 months.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Tracleer®

Detailed Description

This is a multicenter, open-label, single -arm study with bosentan, initial dose of 62.5 mg b.i.d., with a target dose of 125 mg b.i.d. All patients will be assessed for eligibility during the baseline visit (same as Week 16, end of study BREATHE-5 visit), and will have the option to enter into the open-label extension study at a starting dose of 62.5 mg b.i.d., for safety reasons. Visit 2 is required as a safety visit to assess oxygen saturation (SpO2) after 1 week of bosentan treatment. Patients will return for Visit 4 after 4 weeks of treatment, and the dose will be up-titrated to 125 mg b.i.d. or maintained at 62.5 mg b.i.d. at the judgement of the investigator. Data will be collected for a total of 24 weeks or until the sponsor decides to stop the study. If the results from Study AC-052-403 or AC-052-405 demonstrate significant safety issues, this extension study may be terminated at the sponsor's request.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia, NSW 2050
    • Royal Prince Alfred Hospital - Central Clinical School
  • Victoria, Australia, 3050
    • The Royal Melbourne Hospital
• Austria
  • Wien, Austria, AT-1090
    • Universitatsklinikum fur Innere Medizin II
• Belgium
  • Leuven, Belgium, BE-3000
    • UZ Gasthuisberg
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T1Y 6J4
      • The Peter Lougheed Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
• France
  • Paris, France, 75007
    • Hospital Necker-Enfants Malades
• Germany
  • Bad Oeynhausen, Germany, D-32545
    • Herzzentrum NRW
  • Munchen, Germany, D-80636
    • Deutsches Herzzentrum München
• Italy
  • Bologna, Italy, 40138
    • University of Bologna
  • Pavia, Italy, 27100
    • San Matteo Hospital
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Academisch Ziekenhuis Groningen
• Spain
  • Madrid, Spain, 28046
    • Unidad Medico Quirurgica de Cardiologia - Edificio General
• United Kingdom
  • Glasgow, United Kingdom, G11 6NT
    • Scottish Vascular Unit - Western Infirmary
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • BACH Pulmonary Hypertension Service
  • Texas
    • Houston, Texas, United States, 77030-2303
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients stable with PAH upon completion of the BREATHE-5 randomized, double-blind, placebo- controlled 16-week study.
2. For female patients, only non-pregnant women who are surgically sterile, postmenopausal or have documented infertility (over 50 years of age and amenorrheic for at least 1 year), or those of childbearing potential using one of the following methods of contraception: Barrier-type devices (e.g., condom, diaphragm) used ONLY in combination with a spermicide. A double-barrier method is recommended; intrauterine devices (IUDs); oral or implanted contraceptives, if used in combination with a barrier method.
3. Patients providing written informed consent.

Exclusion Criteria:

1. Patients who withdrew prematurely from BREATHE-5, AC-052-405.
2. Patients who are pregnant or nursing.
3. Patients who are receiving epoprostenol or prostacyclin analogues, or are expected to receive any of these drugs during the study.
4. Patients with AST and/or ALT values greater than 3 times the upper limit of normal.
5. Patients with hemoglobin or hematocrit that is more than 30% below the normal range (patients with secondary polycythemia are permitted in the study).
6. Patients with systolic blood pressure < 85 mm Hg.
7. Patients taking phosphodiesterase inhibitors, other endothelin receptor antagonists or are receiving another investigational product.
8. Patients active on organ transplant list.
9. Patients who are receiving or expected to receive glyburide, cyclosporin A or tacrolimus.
10. Patients not able to comply with the protocol or adhere to therapy.

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: Tracleer; The starting dose for all patients will be 62.5 mg b.i.d. At the Week 4 visit, patients who were started on 62.5 mg b.i.d. will be uptitrated to 125 mg b.i.d. if the 62.5 mg b.i.d. dose was well-tolerated.	Drug: Tracleer®; Patients will receive up to 125 mg b.i.d. of Tracleer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6-minute Walk Distance		from baseline to week 24
Change in Borg Dyspnea Index	Borg scale a numerical scale for assessing dyspnea, from 0 representing no dyspnea to 10 as maximal dyspnea.	from baseline to week 24
Number of Participants With a Change in WHO Functional Class	Number of participants with a change in WHO functional class from baseline to week 24. A change from a higher to a lower functional class (i.e. III to II, III to I or II to I) is considered as an improvement.	from baseline to week 24

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Chair: Michael Landzberg, MD, BACH Pulmonary Hypertension Service, Boston, U.S.A.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: August 21, 2006
• First Submitted That Met QC Criteria: August 22, 2006
• First Posted (Estimate): August 23, 2006

Study Record Updates

• Last Update Posted (Estimate): September 22, 2016
• Last Update Submitted That Met QC Criteria: August 16, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: bosentan; Tracleer; PAH related to Eisenmenger physiology
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Congenital Abnormalities; Hypertension, Pulmonary; Heart Defects, Congenital; Cardiovascular Abnormalities; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Eisenmenger Complex; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; Bosentan
• Other Study ID Numbers: AC-052-409

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO