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)

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: UT-15C 0.25 mg; Drug: UT-15C 1 mg; Drug: UT-15C 5 mg

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).

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia
    • Prince Charles Hospital
  • Melbourne, Australia
    • The Alfred Hospital
  • New South Wales
    • Sydney, New South Wales, Australia
      • St. Vincent's Hospital
• Mexico
  • Monterrey, Mexico
    • Unidad de Investigacion Clinica en Medicina (UDICEM)
  • DF
    • Mexico City, DF, Mexico, 14080
      • Instituto Nacional de Cardiologia
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Birmingham
  • California
    • Los Angeles, California, United States, 90073
      • West Los Angeles VA Healthcare Center
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Pulmonary Hypertension Clinic
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Health Care
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia Presbyterian Medical Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical Center
    • Rochester, New York, United States, 14643
      • Mary M Parkes Center for Asthma, Allergy and Pulmonary Care - University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97210
      • Lagacy Clinic Northwest
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern
  • Utah
    • Murray, Utah, United States, 84157-7000
      • Intermountain Medical Center
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo	Drug: Placebo; Placebo
Active Comparator: UT-15C 0.25 mg	Drug: UT-15C 0.25 mg; UT-15C 0.25 mg
Active Comparator: UT-15C 1 mg	Drug: UT-15C 1 mg; UT-15C 1 mg
Active Comparator: UT-15C 5 mg	Drug: UT-15C 5 mg; UT-15C 5 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in six-minute walk distance from Baseline to Week 12	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events	12 weeks
Borg Dyspnea Score	12 weeks
Clinical Worsening Assessment	12 weeks
Dyspnea Fatigue Index	12 weeks
Symptoms of PAH	12 weeks
World Health Organization (WHO) Functional Class	12 weeks
Trough 6-Minute Walk Distance	12 weeks
Trough Borg Dyspnea Score	12 weeks
Pro-B-type natriuretic peptide (Pro-BNP)	12 weeks
Optional hemodynamic parameters	12 weeks
Clinical Laboratory parameters	12 weeks
Electrocardiogram findings	12 weeks

Collaborators and Investigators

• Sponsor: United Therapeutics
• Investigators: Study Director: Kevin Laliberte, PharmD, United Therapeutics

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: September 25, 2008
• First Submitted That Met QC Criteria: September 25, 2008
• First Posted (Estimate): September 26, 2008

Study Record Updates

• Last Update Posted (Estimate): January 30, 2013
• Last Update Submitted That Met QC Criteria: January 29, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Pulmonary Arterial Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: TDE-PH-303