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Efficacy and Safety of Oral UT-15C Tablets to Treat Pulmonary Arterial Hypertension (FREEDOM-C2)

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ClinicalTrials.gov Identifier: NCT00887978
Recruitment Status : Completed
First Posted : April 24, 2009
Results First Posted : January 15, 2013
Last Update Posted : January 15, 2013
Information provided by (Responsible Party):
United Therapeutics

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). Study visits will occur at 4 week intervals for 16 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.

Patients who complete all assessments for 16-weeks will also be eligible to enter an open-label, extension phase study (FREEDOM - EXT).

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Drug: UT-15C SR Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 310 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A 16-Week, International, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of Oral UT-15C Sustained Release Tablets in Subjects With Pulmonary Arterial Hypertension
Study Start Date : June 2009
Actual Primary Completion Date : July 2011
Actual Study Completion Date : July 2011

Arm Intervention/treatment
Placebo Comparator: Placebo
Identical placebo tablets to UT-15C, doses were titrated in the same manner
Drug: Placebo
Experimental: UT-15C SR
Doses were initiated at 0.25 mg BID and increased by 0.25 mg BID every three days (as clinically indicated based on tolerability and symptoms of PAH), to a max dose of 16 mg BID.
Drug: UT-15C SR
treprostinil diolamine sustained release tablets
Other Name: treprostinil diolamine, treprostinil diethanolamine, UT-15C

Primary Outcome Measures :
  1. 6-minute Walk Distance (6MWD) [ Time Frame: Baseline and 16 weeks ]

    Placebo-corrected change in 6MWD from Baseline to Week 16, correlates with the current 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 6MWD was to be assessed between 3 and 6 hours after the morning dose of study drug and background therapy(ies).

Secondary Outcome Measures :
  1. Clinical Worsening Assessment [ Time Frame: Baseline and 16 Weeks ]

    Definition of clinical worsening included patients who met at least one of the following criteria during the 16 weeks of study:

    1. Death (all causes excluding accident)
    2. Transplantation
    3. Atrial septostomy
    4. Hospitalization as a result of right heart failure
    5. Greater than or equal to a 20% decrease in 6MWD from Baseline (or too ill to walk) AND addition of an inhaled prostacyclin analogue, ERA, or PDE-5i
    6. Initiation of parenteral prostacyclin therapy (i.e., epoprostenol, iloprost, or treprostinil) for the treatment of PAH

  2. 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 six-minute walk test (6MWT). The Borg dyspnea score was assessed immediately following the 6MWT. Scores ranged from 0 (for no shortness of breath) to 10 (for the greatest shortness of breath ever experienced).

  3. World Health Organization (WHO) Functional Class [ Time Frame: Baseline and 16 Weeks ]
    Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms.

  4. Symptoms of PAH [ Time Frame: Baseline and 16 Weeks ]
    Symptoms of PAH including fatigue, dyspnea, edema, dizziness, syncope, chest pain and orthopnea were assessed by the physician at Baseline and Week 16. Severity grade values (i.e., 0, 1, 2 or 3) for each symptom were provided each subject. A severity of 0 indicated no symptoms, the maximum severity was 3, indicating severe symptoms. Mean change in symptom severity from Baseline to Week 16 is described.

  5. Dyspnea Fatigue Index [ Time Frame: Baseline and 16 Weeks ]
    The dyspnea-fatigue index was assessed at Baseline and Week 16. Each of the three components of the dyspnea-fatigue index were rated on a scale 0 to 4, with 0 being the worst condition and 4 being the best condition for each component. The dyspnea-fatigue index is computed by summing the three component scores.

  6. N-terminal proBNP (NT-proBNP) [ Time Frame: Baseline and 16 Weeks ]
    Serum N-terminal pro-BNP concentration was assessed at Baseline and Week 16.

  7. Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) [ Time Frame: Baseline and 16 Weeks ]
    Change in CAMPHOR Scores from Baseline to Week 16. The CAMPHOR is a health related quality of life instrument validated for pulmonary hypertension that assesses impairment (symptoms), disability (activities) and quality of life. The questionnaire is divided into three sections; Symptoms (Scores 0-25; high scores indicate more symptoms), Activity (Score 0-30; low score indicates good functioning)and Quality of Life (0-25; high scores indicate poor QoL). The sum of these scores equates to the Total score (0-80). In the CAMPHOR scores, lower scores indicate improvements.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • A subject is eligible for inclusion in this study if all of the following criteria apply:
  • Between 18 and 75 years of age, inclusive.
  • Body weight at least 40 kg (approximately 90 lbs.)
  • PAH that is either idiopathic/heritable; associated with appetite suppressant or toxin use; associated with collagen vascular disease; associated with repaired congenital shunts; 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.
  • Baseline six-minute walk distance (6MWD) between 150-425 meters
  • Previous testing (e.g., right heart catheterization, echocardiography) consistent with the diagnosis of PAH.
  • Reliable and cooperative with protocol requirements.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00887978

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Sponsors and Collaborators
United Therapeutics
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Study Chair: Lewis Rubin, MD University of California, San Diego
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT00887978    
Other Study ID Numbers: TDE-PH-308
First Posted: April 24, 2009    Key Record Dates
Results First Posted: January 15, 2013
Last Update Posted: January 15, 2013
Last Verified: December 2012
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Pulmonary Arterial Hypertension
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Antihypertensive Agents