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 has been completed.
Sponsor:
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT00325442
First received: May 11, 2006
Last updated: May 6, 2013
Last verified: May 2013
  Purpose

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).


Condition Intervention Phase
Pulmonary Hypertension
Drug: Oral treprostinil (UT-15C) sustained release tablets
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by United Therapeutics:

Primary Outcome Measures:
  • Six Minute Walk Distance (6MWD) [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • Borg Dyspnea Score [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]
    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).

  • Clinical Worsening Assessment [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]

    Definition of clinical worsening required one of the following:

    1. Death (all causes excluding accident)
    2. Transplantation or atrial septostomy
    3. Clinical deterioration as defined by:

      1. Hospitalization as a result of PAH, or
      2. ≥ 20% decrease in 6-minute walk distance from Baseline (or too ill to walk) and a decrease in WHO functional class And
      3. Initiation of new PAH specific therapy (i.e., ERA, PDE5I, prostacyclin).

  • Dyspnea-Fatigue Index [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]
    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.

  • World Health Organization Functional Classification for PAH [ Time Frame: Week 16 ] [ Designated as safety issue: No ]

    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.


  • Six Minute Walk Distance (6MWD) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]

    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.


  • Six Minute Walk Distance (6MWD) [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]

    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.


  • Six Minute Walk Distance (6MWD) [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]

    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.


  • Change in Symptoms of PAH From Baseline to Week 16 [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 354
Study Start Date: October 2006
Study Completion Date: December 2010
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active
Subjects assigned to active therapy with UT-15C 0.25, 0.5, 1, or 5 mg oral tablets.
Drug: Oral treprostinil (UT-15C) sustained release tablets
UT-15C 0.25, 0.5, 1, or 5 mg oral tablets by mouth every 12 hours
Placebo Comparator: Placebo Arm
Subjects assigned to placebo 0.25, 0.5, 1, or 5 mg oral tablets.
Drug: Placebo
Placebo 0.25, 0.5, 1, or 5 mg oral tablets by mouth every 12 hours

  Eligibility

Ages Eligible for Study:   12 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00325442

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Sponsors and Collaborators
United Therapeutics
  More Information

No publications provided by United Therapeutics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT00325442     History of Changes
Other Study ID Numbers: TDE-PH-301
Study First Received: May 11, 2006
Results First Received: January 18, 2013
Last Updated: May 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by United Therapeutics:
Pulmonary Arterial Hypertension

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Treprostinil
Phosphodiesterase 5 Inhibitors
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014