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Completed

NCT Number: 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)

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).

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Key information

Conditions

Pulmonary Hypertension Cardiovascular Diseases Hypertension Hypertension, Pulmonary Lung Diseases Pulmonary Arterial Hypertension Respiratory Tract Diseases Vascular Diseases

Age range

12 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

St. Vincent's Hospital, Sydney, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Oral treprostinil (UT-15C) Sustained Release Tablets

Drug

UT-15C 0.25, 0.5, 1, or 5 mg oral tablets by mouth every 12 hours

Placebo

Drug

Placebo 0.25, 0.5, 1, or 5 mg oral tablets by mouth every 12 hours

Primary outcomes

  1. Six Minute Walk Distance (6MWD)

    Time frame: Baseline and 16 Weeks

    Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 16, correlates with the historical clinical standard for assessing patient functional status in the treatment of PAH and is considered an objective measure of patient functional status by the American Thoracic Society (ATS).

    The six minute walk test was to be conducted 3 to 6 hours after the previous dose of study drug.

Secondary outcomes

  1. Borg Dyspnea Score

    Time frame: Baseline and 16 Weeks

    The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea experienced during the 6-minute walk test. The Borg dyspnea score was assessed immediately following the 6-minute walk test. Scores ranged from 0 (for no shortness of breath) to 10 (for greatest shortness of breath ever experienced).

  2. Clinical Worsening Assessment

    Time frame: Baseline and 16 Weeks

    Definition of clinical worsening required one of the following:

    • Death (all causes excluding accident)
    • Transplantation or atrial septostomy
    • Clinical deterioration as defined by:
    • Hospitalization as a result of PAH, or
    • ≥ 20% decrease in 6-minute walk distance from Baseline (or too ill to walk) and a decrease in WHO functional class And
    • Initiation of new PAH specific therapy (i.e., ERA, PDE5I, prostacyclin).

  3. Dyspnea-Fatigue Index

    Time frame: Baseline and 16 Weeks

    The dyspnea-fatigue index has three components, each rated on a scale of 0 to 4, for the magnitude of the task that evokes dyspnea or fatigue, the magnitude of the pace (or effort) with which the task is performed and the associated functional impairment in general activities. The ratings for each component were added to form an aggregate score, which could range from 0, for the worst condition, to 12, for the best.

  4. World Health Organization Functional Classification for PAH

    Time frame: Week 16

    Class I: Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope.

    Class II: Patients with pulmonary hypertension resulting in slight limitation of physical activity. These patients are comfortable at rest, but ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope.

    Class III: Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope.

    Class IV: Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may be present even at rest. Discomfort is increased by any physical activity.

  5. Six Minute Walk Distance (6MWD)

    Time frame: Baseline and 12 weeks

    Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 12, correlates with the historical clinical standard for assessing patient functional status in the treatment of PAH and is considered an objective measure of patient functional status by the American Thoracic Society (ATS).

    The six minute walk test was to be conducted 3 to 6 hours after the previous dose of study drug.

  6. Six Minute Walk Distance (6MWD)

    Time frame: Baseline and 8 weeks

    Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 8, correlates with the historical clinical standard for assessing patient functional status in the treatment of PAH and is considered an objective measure of patient functional status by the American Thoracic Society (ATS).

    The six minute walk test was to be conducted 3 to 6 hours after the previous dose of study drug.

  7. Six Minute Walk Distance (6MWD)

    Time frame: Baseline and 4 weeks

    Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 4, correlates with the historical clinical standard for assessing patient functional status in the treatment of PAH and is considered an objective measure of patient functional status by the American Thoracic Society (ATS).

    The six minute walk test was to be conducted 3 to 6 hours after the previous dose of study drug.

  8. Change in Symptoms of PAH From Baseline to Week 16

    Time frame: Baseline and 16 weeks

    Defined symptoms of PAH including fatigue, dyspnea, edema, dizziness, syncope, chest pain, and orthopnea were assessed at Baseline prior to starting study drug and during the Treatment Phase at Week 16. Severity grade values (i.e., 0, 1, 2, or 3 in increasing severity) were assigned for each symptom. The outcome data describes the change in severity values from Baseline to Week 16 for each defined symptom of PAH.

Sponsors and collaborators

Lead sponsor

United Therapeutics

Industry

Registry information

Official study 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

Important dates

Study start
2006
Primary completion
2008
Study completion
2010
First posted
May 12, 2006
Registry last updated
Aug 2, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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