Clinical trial NCT00760916: FREEDOM DR: Oral Treprostinil in Combination With an Endothelin Receptor Antagonist (ERA) and/or a Phosphodiesterase-5 (PDE-5) Inhibitor or as Monotherapy for the Treatment of Pulmonary Arterial Hypertension (PAH)
Official title: FREEDOM DR: An International, Multi-Center, 12-Week, Double Blind, Randomized, Placebo-Controlled, Parallel Group Study Followed by a 12-Week Open-Label Extension Study to Assess the Efficacy, Safety, and Dose Response of UT-15C SR in Subjects With Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Pulmonary Hypertension
Keywords: Pulmonary Arterial Hypertension
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2008-09-26
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is an international, multi-center, randomized, double-blind, placebo-controlled study in subjects with PAH who are currently receiving approved therapy for their PAH (i.e., endothelin receptor antagonist and/or phosphodiesterase-5 inhibitor)or as a monotherapy treatment. Study visits will occur at 4 week intervals for 12 weeks with the key measure of efficacy being the 6-minute walk test. Study procedures include routine blood tests, medical history, physical exams, disease evaluation, and exercise tests. At the end of the first 12-weeks, the patient will be un-blinded. Patients will continue with another 12-Week open label portion with visits occuring at 4-week intervals.

Patients who complete all assessments for 24-weeks will also be eligible to enter a 36 month open-label, extension phase study (FREEDOM - EXT).

Detailed description: This study is an international, multi-center, randomized, double-blind, placebo-controlled study in subjects with PAH who are currently receiving approved therapy for their PAH (i.e., endothelin receptor antagonist and/or phosphodiesterase-5 inhibitor)or as a monotherapy treatment. Study visits will occur at 4 week intervals for 12 weeks with the key measure of efficacy being the 6-minute walk test. Study procedures include routine blood tests, medical history, physical exams, disease evaluation, and exercise tests. At the end of the first 12-weeks, the patient will be un-blinded. Patients will continue with another 12-Week open label portion with visits occuring at 4-week intervals.

Patients who complete all assessments for 24-weeks will also be eligible to enter a 36 month open-label, extension phase study (FREEDOM - EXT).

Eligibility criteria: Inclusion Criteria:

* Between 18 and 70 years of age, inclusive
* Body weight at least 50 kilograms
* PAH that is either idiopathic/familial; associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥ 5 years); associated with collagen vascular disease; associated with HIV.
* 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 or not currently receiving approved PAH therapy.
* 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: Change in six-minute walk distance from Baseline to Week 12
timeFrame: 12 weeks
Secondary outcomes:
measure: Borg Dyspnea Score
timeFrame: 12 weeks
measure: Clinical Worsening Assessment
timeFrame: 12 weeks
measure: Dyspnea Fatigue Index
timeFrame: 12 weeks
measure: Symptoms of PAH
timeFrame: 12 weeks
measure: World Health Organization (WHO) Functional Class
timeFrame: 12 weeks
measure: Trough 6-Minute Walk Distance
timeFrame: 12 weeks
measure: Trough Borg Dyspnea Score
timeFrame: 12 weeks
measure: Pro-B-type natriuretic peptide (Pro-BNP)
timeFrame: 12 weeks
measure: Optional hemodynamic parameters
timeFrame: 12 weeks
measure: Adverse events
timeFrame: 12 weeks
measure: Clinical Laboratory parameters
timeFrame: 12 weeks
measure: Electrocardiogram findings
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
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: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Pulmonary Hypertension Clinic
state: Colorado
city: Iowa City
country: United States
facility: University of Iowa Health Care
state: Iowa
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: Washington University Hospital
state: Missouri
city: New York
country: United States
facility: Weill Cornell Medical Center
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: 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: Lagacy 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: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Prince Charles Hospital
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cardiologia
state: DF
city: Monterrey
country: Mexico
facility: Unidad de Investigacion Clinica en Medicina (UDICEM)
Study officials:
affiliation: United Therapeutics
name: Kevin Laliberte, PharmD
role: STUDY_DIRECTOR
References: