Clinical trial NCT00325442: FREEDOM-C: Oral Treprostinil in Combination With an Endothelin Receptor Antagonist (ERA) and/or a Phosphodiesterase-5 (PDE-5) Inhibitor for the Treatment of Pulmonary Arterial Hypertension (PAH)
Official title: A 16-Week, International, Multicenter, Double-Blind, Randomized, Placebo-Controlled Comparison of the Efficacy and Safety of Oral UT-15C Sustained Release Tablets in Combination With an Endothelin Receptor Antagonist and/or a Phosphodiesterase-5 Inhibitor in Subjects With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Hypertension
Keywords: Pulmonary Arterial Hypertension
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2006-05-12
Enrollment: 354
Sex: ALL
Minimum age (years): 12
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was an international, multi-center, randomized, double-blind, placebo-controlled study in subjects with PAH who were currently receiving approved therapy for their PAH (i.e., endothelin receptor antagonist and/or phosphodiesterase-5 inhibitor). Study visits occurred at 4 week intervals for 16 weeks; the key measure of efficacy was the 6-minute walk test. Study procedures included routine blood tests, medical history, physical exams, disease evaluation, and exercise tests. One optional substudy was also a part of FREEDOM-C at select centers - a hemodynamic substudy with a right heart catheterization at Baseline and Week 16.

Patients who completed all assessments for 16-weeks were also eligible to enter an open-label, extension phase study (FREEDOM - EXT).


Eligibility criteria: Inclusion Criteria:

* Between 12 and 70 years of age, inclusive.
* Body weight at least 45 kg (approximately 100 pounds).
* PAH that is either idiopathic/heritable (including PAH associated with appetite suppressant/toxin use); PAH associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥ 5 years); PAH associated with collagen vascular disease; or PAH associated with HIV.
* Baseline 6-minute walk distance between 150 and 450 meters, inclusive.
* Currently receiving an approved endothelin receptor antagonist and/or an approved phosphodiesterase-5 inhibitor for at least 90 days and on a stable dose for at least the last 30 days.
* Previous testing (e.g., right heart catheterization, echocardiography) consistent with the diagnosis of PAH.
* Reliable and cooperative with protocol requirements.

Exclusion Criteria:

* Nursing or pregnant.
* Received a prostacyclin within the past 30 days.
* PAH due to conditions other than noted in the above inclusion criteria.
* History of uncontrolled sleep apnea, renal insufficiency, anemia, left sided heart disease, uncontrolled systemic hypertension, or parenchymal lung disease.
* Use of an investigational drug within 30 days of Baseline.

Primary outcomes:
measure: Six Minute Walk Distance (6MWD)
timeFrame: Baseline and 16 Weeks
Secondary outcomes:
measure: Borg Dyspnea Score
timeFrame: Baseline and 16 Weeks
measure: Clinical Worsening Assessment
timeFrame: Baseline and 16 Weeks
measure: Dyspnea-Fatigue Index
timeFrame: Baseline and 16 Weeks
measure: World Health Organization Functional Classification for PAH
timeFrame: Week 16
measure: Six Minute Walk Distance (6MWD)
timeFrame: Baseline and 12 weeks
measure: Six Minute Walk Distance (6MWD)
timeFrame: Baseline and 8 weeks
measure: Six Minute Walk Distance (6MWD)
timeFrame: Baseline and 4 weeks
measure: Change in Symptoms of PAH From Baseline to Week 16
timeFrame: Baseline and 16 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama-Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialist
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Health Science Center
state: Arizona
city: Los Angeles
country: United States
facility: West Los Angeles VA Healthcare Center
state: California
city: Palo Alto
country: United States
facility: Stanford University, Pulmonary and Critical Care
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: University of California-San Francisco
state: California
city: Torrance
country: United States
facility: Harbour-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: The Children's Hospital
state: Colorado
city: Aurora
country: United States
facility: Pulmonary Hypertension Clinic
state: Colorado
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa
country: United States
facility: University of Iowa Health Care
state: Iowa
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: John's Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University Hospital
state: Missouri
city: New York
country: United States
facility: Columbia Presbyterian Medical Center
state: New York
city: Rochester
country: United States
facility: Mary M Parkes Center for Asthma, Allergy and Pulmonary Care
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Legacy Clinic Northwest
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine, Pulmonary & Critical Care
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Fairfax
country: United States
facility: Inova Transplant Center
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Heart Care Associates
state: Wisconsin
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: The Prince Charles Hospital
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Wien
country: Austria
facility: Universitaet Wien
city: Brussels
country: Belgium
facility: Hospital Erasme
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg
city: Calgary
country: Canada
facility: Respiratory Research
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Coastal Health Respiratory Clinic
state: British Columbia
city: London
country: Canada
facility: Lab London Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: SMBD Jewish General Hospital
state: Quebec
city: Brest
country: France
facility: Hospital Cavale Blanche
city: Clamart
country: France
facility: Hospital Antoine Beclere
city: Lille Cedex
country: France
facility: Hospital Claude Huriez
city: Lyon
country: France
facility: Hôpital Louis Pradel
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital Ltd
city: Jerusalem
country: Israel
facility: Hadassah Ein-Kerem Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Tel Hashomer Medical Center
city: Bologna
country: Italy
facility: Universita degli Studi Bologna
city: Rome
country: Italy
facility: Universita "La Sapienza" Roma
city: Amsterdam
country: Netherlands
facility: Hospital Vrije Universiteit
city: Warsaw
country: Poland
facility: National Tuberculosis and Lung Disease Research Institute
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
city: Barcelona
country: Spain
facility: Hospital Valle Hebron
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
city: Glasgow
country: United Kingdom
facility: Western Infirmary
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
Study officials:
References:
citation: Tapson VF, Torres F, Kermeen F, Keogh AM, Allen RP, Frantz RP, Badesch DB, Frost AE, Shapiro SM, Laliberte K, Sigman J, Arneson C, Galie N. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial. Chest. 2012 Dec;142(6):1383-1390. doi: 10.1378/chest.11-2212.