Efficacy and Safety of Oral UT-15C Tablets to Treat Pulmonary Arterial Hypertension

Pulmonary Hypertension Clinical Trial

— FREEDOM-C2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00887978
• Other study ID #: TDE-PH-308
• Status: Completed
• Phase: Phase 3
• First received: April 23, 2009
• Last updated: December 7, 2012
• Start date: June 2009
• Est. completion date: July 2011

Study information

• Verified date: December 2012
• Source: United Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 310
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• UT-15C SR
treprostinil diolamine sustained release tablets
• Placebo

Locations

Country	Name	City	State
Belgium	University Hospital Gasthuisberg	Leuven
Canada	University of Calgary	Calgary	Alberta
Canada	University of Alberta Hospitals	Edmonton	Alberta
Canada	London Health Sciences Center	London	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Vancouver Coastal Health Respiratory Clinic	Vancouver	British Columbia
France	Hospital Cavale Blanche	Brest
France	Hospital Claude Huriez	Lille	Cedex
France	Hospital Haut Leveque	Pessac	Cedex
Germany	Universitaetsklinikum Dresden	Dresden
Germany	University Hospital Greifswald	Greifswald
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Israel	Lady Davis Carmel Medical Centre	Haifa
Israel	Pulmonology Department Rambam Medical Center	Haifa
Israel	Pulmonary institute	Ramat Gan
Italy	Azienda Ospedaliera Universitaria	Naples
Netherlands	VUMC	Amsterdam
Portugal	Hospital de Santa Marta	Lisboa
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Sweden	Lund University Hospital	Lund
United Kingdom	Royal Free Hospital NHS Trust	London
United States	Emory University School of Medicine	Atlanta	Georgia
United States	University of Colorado Health Science Center	Aurora	Colorado
United States	University of Alabama-Birmingham	Birmingham	Alabama
United States	Pulmonary Critical Care Medicine, Brigham and Women's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of Chicago Hospitals	Chicago	Illinois
United States	Lindner Center	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	UT Southwestern	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Transplant Center	Falls Church	Virginia
United States	University of California, San Francisco-Fresno	Fresno	California
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Florida-Jacksonville	Jacksonville	Florida
United States	Kansas University Medical Center	Kansas City	Kansas
United States	UCSD Medical Center	La Jolla	California
United States	West Los Angeles VA Healthcare Center	Los Angeles	California
United States	Kentuckiana Pulmonary Associates	Louisville	Kentucky
United States	Winthrop University Hospital	Mineola	New York
United States	Intermountain Medical Center	Murray	Utah
United States	Columbia University Presbyterian Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialist, LTD	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Legacy Pulmonary Northwest	Portland	Oregon
United States	Maine Medical Center	Portland	Maine
United States	OHSU	Portland	Oregon
United States	Mary M Parkes Center for Asthma, Allergy and Pulmonary Care	Rochester	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	UC Davis Medical Center	Sacramento	California
United States	Washington University Hospital	St. Louis	Missouri
United States	The University of Toledo	Toledo	Ohio
United States	Harbor-UCLA Medical Center	Torrance	California
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
United Therapeutics

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Israel,  Italy,  Netherlands,  Portugal,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6-minute Walk Distance (6MWD)	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).	Baseline and 16 weeks	No
Secondary	Clinical Worsening Assessment	Definition of clinical worsening included patients who met at least one of the following criteria during the 16 weeks of study: Death (all causes excluding accident); Transplantation; Atrial septostomy; Hospitalization as a result of right heart failure; 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; Initiation of parenteral prostacyclin therapy (i.e., epoprostenol, iloprost, or treprostinil) for the treatment of PAH	Baseline and 16 Weeks	Yes
Secondary	Borg Dyspnea Score	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).	Baseline and 16 Weeks	No
Secondary	World Health Organization (WHO) Functional Class	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.	Baseline and 16 Weeks	No
Secondary	Symptoms of PAH	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.	Baseline and 16 Weeks	No
Secondary	Dyspnea Fatigue Index	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.	Baseline and 16 Weeks	No
Secondary	N-terminal proBNP (NT-proBNP)	Serum N-terminal pro-BNP concentration was assessed at Baseline and Week 16.	Baseline and 16 Weeks	No
Secondary	Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)	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.	Baseline and 16 Weeks	No