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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT00887978
First received: April 23, 2009
Last updated: December 7, 2012
Last verified: December 2012
  Purpose

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 Intervention Phase
Pulmonary Hypertension
Drug: UT-15C SR
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by United Therapeutics:

Primary Outcome Measures:
  • 6-minute Walk Distance (6MWD) [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]

    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:
  • Clinical Worsening Assessment [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: Yes ]

    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

  • 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 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).

  • World Health Organization (WHO) Functional Class [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]
    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.

  • Symptoms of PAH [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]
    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.

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

  • N-terminal proBNP (NT-proBNP) [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]
    Serum N-terminal pro-BNP concentration was assessed at Baseline and Week 16.

  • Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 310
Study Start Date: June 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00887978

  Show 62 Study Locations
Sponsors and Collaborators
United Therapeutics
Investigators
Study Chair: Lewis Rubin, MD University of California, San Diego
  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: NCT00887978     History of Changes
Other Study ID Numbers: TDE-PH-308
Study First Received: April 23, 2009
Results First Received: November 2, 2012
Last Updated: December 7, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Treprostinil
Antihypertensive Agents
Cardiovascular Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014