Clinical trial NCT00325403: FREEDOM - M: Oral Treprostinil as Monotherapy for the Treatment of Pulmonary Arterial Hypertension (PAH)
Official title: A 12-Week, International, Multicenter, Double-Blind, Randomized, Placebo-Controlled Comparison of the Efficacy and Safety of Oral UT-15C Sustained Release Tablets 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: 349
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
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, multicenter, randomized (2:1 active:placebo), double-blind, placebo-controlled study in subjects with PAH who were NOT currently receiving approved therapy for their PAH. Study visits occurred at 4 week intervals for 12 weeks (with an additional visit at Week 11) with the key measure of efficacy being the 6-minute walk test. Study procedures included routine blood tests, medical history, physical exams, disease evaluation, and exercise tests. Two optional substudies were also a part of FREEDOM-M at select centers - a hemodynamic substudy with a right heart catheterization at Baseline and Week 12 and a genetics and biomarkers substudy with blood samples collected at Baseline and Week 12.

Patients who completed all assessments for 12 weeks were also eligible to enter an open-label, extension phase study (FREEDOM - EXT).


Eligibility criteria: Inclusion Criteria:

* Between 12 and 75 years of age, inclusive.
* Body weight at least 40 kg with a Body Mass Index \< 45
* PAH that is either idiopathic/heritable; associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥ 5 years); associated with collagen vascular disease; associated with HIV.
* Previous testing (e.g., right heart catheterization, echocardiography) consistent with the diagnosis of PAH.
* Baseline 6-minute walk distance between 200 and 425 meters, inclusive.
* Reliable and cooperative with protocol requirements.

Exclusion Criteria:

* Nursing or pregnant.
* Currently receiving an endothelin receptor antagonist, a phosphodiesterase-5 inhibitor, or prostacyclin within 30 days of Baseline.
* 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 Week 12
Secondary outcomes:
measure: Six Minute Walk Distance (6MWD)
timeFrame: Baseline and Week 11
measure: Six Minute Walk Distance (6MWD)
timeFrame: Baseline and Week 8
measure: Six Minute Walk Distance (6MWD)
timeFrame: Baseline and Week 4
measure: Clinical Worsening Assessment
timeFrame: Baseline and Week 12
measure: World Health Organization Functional Classification for PAH
timeFrame: Baseline and Week 12
measure: Borg Dyspnea Score
timeFrame: Baseline and Week 12
measure: Dyspnea-Fatigue Index
timeFrame: Baseline and Week 12
measure: Symptoms of PAH
timeFrame: Baseline and Week 12
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: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Fresno
country: United States
facility: University of California, San Francisco-Fresno
state: California
city: Los Angeles
country: United States
facility: West Los Angeles VA Healthcare Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Health Science Center
state: Colorado
city: Jacksonville
country: United States
facility: University of Florida - Shands Hospital
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Hospitals
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Associates
state: Kentucky
city: Alexandria
country: United States
facility: Alexandria Cardiology Clinic
state: Louisiana
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: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University Hospital
state: Missouri
city: Omaha
country: United States
facility: Nebraska Medical Center
state: Nebraska
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
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 - University of Rochester
state: New York
city: Cincinnati
country: United States
facility: The Lindner Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
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: Portland
country: United States
facility: Oregon Health and Science University
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: Dallas
country: United States
facility: University of Texas 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: University of Texas Health Science Center at San Antonio
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
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: 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: Peter Lougheed Centre
state: Alberta
city: London
country: Canada
facility: London Health Science Centre
state: Ontario
city: Montreal
country: Canada
facility: SMBD Jewish General Hospital
state: Quebec
city: Beijing
country: China
facility: Beijing Shijitan Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Clamart
country: France
facility: Hospital Antoine Beclere
city: Hyderbad
country: India
facility: PRIME Hospitals
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Care Institute of Medical Science
state: Gujarat
city: Ahmedabad
country: India
facility: Lifecare Institute of Medical Sciences & Research
state: Gujarat
city: Bangalore
country: India
facility: Narayana Hrudayalaya Institute of Medical Sciences
state: Karnataka
city: Parel Mumbai
country: India
facility: Asian Heart Institute and Research Centre
state: Maharashtra
city: Pune
country: India
facility: Poona Hospital and Research Centre
state: Maharashtra
city: Chennai
country: India
facility: Sri Ramachandra Medical College
state: Tamil Nadu
city: Coimbatore
country: India
facility: G. Kuppuswamy Naidu Memorial Hospital
state: Tamil Nadu
city: Chennai, Tamil Nadu
country: India
facility: K. S. Hospital
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
city: Pune
country: India
facility: Ruby Hall Clinic
city: Visakhapatnam, Andra Pradesh
country: India
facility: Care Hospital
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: Mexico City
country: Mexico
facility: Instituto Nacional de Cardiologia
state: DF
city: Monterrey
country: Mexico
facility: Hospital Universitario UANL
state: NL
city: Monterrey
country: Mexico
facility: Unidad de Investigacion Clinica en Medicina (UDICEM)
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum (VUCM)
city: Kraków
country: Poland
facility: Krakowski Szpital Specjalistyczny im. (Kraków Specialist Hospital)
city: Warsaw
country: Poland
facility: National Tuberculosis and Lung Disease Research Institute
city: Wroclaw
country: Poland
facility: Wojewódzki Szpital Specjalistyczny we Wroclawiu (Provincial Specialist Hospital in Wrocław)
city: Guaynabo
country: Puerto Rico
facility: Auxilio Mutuo Hospital
Study officials:
affiliation: United Therapeutics
name: Kevin Laliberte, PharmD
role: STUDY_DIRECTOR
References:
citation: Jing ZC, Parikh K, Pulido T, Jerjes-Sanchez C, White RJ, Allen R, Torbicki A, Xu KF, Yehle D, Laliberte K, Arneson C, Rubin LJ. Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial. Circulation. 2013 Feb 5;127(5):624-33. doi: 10.1161/CIRCULATIONAHA.112.124388. Epub 2013 Jan 10.