An Open-Label Extension Trial of UT-15C Sustained-release (SR) in Subjects With Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

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Official title:

An Open-Label Extension Trial of UT-15C SR in Subjects With Pulmonary Arterial Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01027949
• Other study ID #: TDE-PH-304
• Status: Completed
• Phase: Phase 3
• Start date: January 16, 2007
• Est. completion date: February 12, 2020

Study information

• Verified date: April 2021
• Source: United Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study provided/continued to provide oral treprostinil (UT-15C SR; treprostinil diethanolamine) to eligible subjects who participated in Studies TDE-PH-202, TDE-PH-203, TDE-PH-205, TDE-PH-301, TDE-PH-302, and TDE-PH-308. The study assessed the long term safety of oral treprostinil and the effect of continued treatment with oral treprostinil on exercise capacity after 1 year of treatment.

Description:

This was an international, multicenter, open-label study designed to provide oral treprostinil for eligible subjects who participated in Studies TDE-PH-301, TDE-PH-302, TDE-PH-308, TDE-PH-202, TDE PH 203, and TDE-PH-205. Subjects randomly allocated to receive oral treprostinil in Studies TDE-PH-301, TDE-PH-302, or TDE-PH-308 and enrolled in this open-label study completed visits at Months 6, 12, 24, 36, and yearly visits thereafter. Subjects randomly allocated to receive placebo in Studies TDE-PH-301, TDE-PH-302, or TDE-PH-308 completed visits at Months 3, 6, 12, 24, 36, and yearly visits thereafter. Subjects that transitioned from Studies TDE-PH-202, TDE-PH-203, and TDE-PH-205 (that had an open-label study design) followed the regimen for subjects receiving oral treprostinil. A 6-Minute Walk Test (6MWT) and Borg dyspnea score were conducted at the visit which occurred 12 months after the subject's first exposure to oral treprostinil.

Adverse events (AEs) were reported continuously throughout the study; any AEs ongoing at the time of discharge from Studies TDE PH-301, TDE PH-302, TDE-PH-308, TDE-PH-202, TDE-PH-203, and TDE-PH-205 were recorded as AEs and marked as "ongoing from previous study" in the subject's electronic Case Report Form (eCRF). Study drug dosing and pulmonary arterial hypertension (PAH) concomitant medication usage were assessed at each scheduled study visit and recorded in the subject's eCRF.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 894
• Est. completion date: February 12, 2020
• Est. primary completion date: February 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

1. The subject remained on study drug and completed all assessments during the Treatment Phase of the previous study (TDE-PH-202, TDE-PH-203, TDE-PH-205, TDE-PH-301, TDE PH-302, or TDE-PH-308) OR the subject permanently discontinued study drug during the Treatment Phase of the previous study due to clinical worsening (as defined in the protocol of the previous study), completed premature termination assessments prior to discontinuing study drug, completed all remaining scheduled study visits, AND received placebo during the Treatment Phase of the previous studies OR the subject was randomized into Group 1 or Group 2 in Study TDE PH 202, permanently discontinued study drug during the 12-week Treatment Phase due to clinical worsening, completed all premature termination assessments prior to discontinuing study drug, and completed all remaining scheduled study visits and assessments (with the exception of the hemodynamic measurements) through Week 12. Such subjects should have started treatment with oral treprostinil in the open-label study at 0.25 mg twice daily (BID).

2. The subject voluntarily gave informed consent to participate in the study.

3. Women of childbearing potential includes any female who had experienced menarche and who had not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or was not postmenopausal (defined as amenorrhea for at least 12 consecutive months). Sexually active women of childbearing potential must have used 2 effective forms of contraception during the length of the study. Medically acceptable forms of effective contraception included: (1) approved hormonal contraceptives (such as birth control pills), (2) barrier methods (such as a condom or diaphragm) used with a spermicide, (3) an intrauterine device, (4) partner vasectomy, or (5) abstinence. Males participating in the study must have used a condom during the length of the study, and for at least 48 hours after discontinuing study medication. Protocol Amendment A.1AU included the required assessment for Austrian subjects to perform urine pregnancy tests every 4 weeks during the study.

Exclusion Criteria:

1. The subject permanently discontinued study drug during the previous study (TDE PH 202, TDE-PH-203, TDE PH 205, TDE-PH-301, TDE-PH-302, or TDE PH 308) due to treatment-related adverse events (AEs).

2. The subject permanently discontinued study drug during the Treatment Phase of the previous study (TDE-PH-202, TDE-PH-203, TDE-PH-205, TDE-PH-301, TDE-PH-302, or TDE-PH-308) due to clinical worsening (as defined in those study protocols) and did not undergo premature termination assessments prior to discontinuing study drug, and/or did not complete all remaining study visits through the final scheduled visit.

3. The subject prematurely discontinued study drug during the Treatment Phase of the previous study due to clinical worsening (as defined in those study protocols), completed premature termination assessments prior to discontinuing study drug, completed all remaining scheduled study visits AND received oral treprostinil during the Treatment Phase of the previous study (TDE PH-202, TDE-PH-203, TDE-PH-301, TDE-PH-302, or TDE PH-308). Subjects enrolled in Study TDE-PH-202 who were randomized into the individual maximum tolerated dose (iMTD) group who clinically worsened could not participate. Subjects who permanently discontinued study drug during the 12-week Treatment Phase due to treatment-related AEs were not eligible even if they completed all remaining scheduled study visits. Subjects who permanently discontinued study drug during the 12 week Treatment Phase and did not undergo premature termination assessments prior to discontinuing study drug and/or who did not complete all remaining study visits through the Week 12 visit were also not eligible.

4. The subject developed any concurrent illness or condition during the conduct of the previous study, including but not restricted to: sleep apnea, chronic renal insufficiency, anemia, uncontrolled systemic hypertension, or left sided heart disease, unless their physician felt that entry into this study would not be detrimental to their overall health.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Oral Treprostinil
Oral sustained release tablet, twice or thrice daily. Open label study with active drug, no other intervention arms.

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Chermside West
Australia	Heart/Lung Transplant Unit - St. Vincent's Hospital	Darlinghurst
Australia	The Alfred Hospital	Melbourne
Australia	Royal Perth Hospital	Perth
Austria	Medical University Graz	Wein
Austria	Medizininische Universitaet Wien	Wien
Austria	Universitaetsklinik für Innere Medizin Innsbruck	Wien
Belgium	Department of Cardiology Erasme University Hospital	Brussels
Belgium	University Hospital Gasthuisberg	Leuven
Canada	Peter Lougheed Centre	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Sir Mortimer B. Davis Jewish General Hospital	Montréal	Quebec
Canada	London Health Sciences Center Victoria Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Vancouver Coastal Health Authority Vancouver General Hospital	Vancouver	British Columbia
China	Beijing Shijitan Hospital, Cadres Respiratory Department	Beijing
China	Peking Union Medical College Hospital, Respiratory Medicine Department	Beijing
China	Shanghai Pulmonary Hospital, Respiratory Medicine Department	Shanghai
France	PMAC, Clinique de Pneumologie	Bernin
France	Centre d'Investigation Clinique Hôpital La Cavale Blanche - CHU Brest	Brest
France	Hospital Antoine Beclere	Clamart
France	Hospital Claude Huriez	Lille Cedex
France	Hôpital Louis Pradel	Lyon
France	CHU Arnaud de Villeneuve - Service maladies respiratoires	Montpellier cedex 5
France	Service Chirurgie Thoracique, Hôpital Haut Levêque	Pessac	Pessac Cedex
France	Service de Pneumologie Centre de Competence pour l'HTAP- Pole des Voies Respiratoires Hôpital Larrey	Toulouse
Germany	Universitätsklinikum Dresden Abtl. Pneumologie	Dresden
Germany	University Hospital Greifswald	Greifswald
Germany	DRK Kliniken Berlin Köpenick	Hamburg
Germany	Universitatsklinikum Hamburg Eppendorf	Hamburg
Germany	Universitätsklinkium Köln Klinik III für Innere Medizin	Hamburg
Germany	Zentrum für Lungenhochdruck Thoraxklinik am Universitätsklinikum Heidelberg	Hamburg
Germany	Medizinische Hochschule Hannover (MHH)	Hannover
Germany	Dept. of Internal Medicine III University Heidelberg	Heidelberg
India	Care Institute of Medical Sciences	Ahmedabad	Gujarat
India	Life Care Institute of Medical Sciences & Research	Ahmedabad
India	Narayana Hrudayalaya Hospitals	Bangalore	Karnataka
India	Sri Ramachandra Medical College & Research Institute	Chennai
India	G. Kuppuswamy Naidu Memorial Hospital	Coimbatore
India	PRIME Hospitals	Hyderabad
India	Asian Heart Institute & Research Centre Pvt. Ltd.	Mumbai	Maharashtra
India	Sir Ganga Ram Hospital	New Delhi
India	Poona Hospital and Research Centre	Pune	Maharashtra
India	Ruby Hall Clinic	Pune
India	Queen's NRI Hospital	Visakhapatnam
Ireland	Pulmonary Hypertension Unit Centre for Lung Health Mater Misericordiae University Hospital	Dublin
Israel	Rambam Medical Center	Haifa
Israel	The Lady Davis Carmel Medical Center	Haifa
Israel	Hadassah Hebrew University Medical Center	Jerusalem
Israel	Pulmonary Institute Rabin Medical Center (Belinson Kampus)	Petah Tiqva
Israel	Pulmonary Institute Chaim Sheba Medical Center	Ramat Gan
Italy	Policlinico S. Orsola Malpighi - Università degli studi di Bologna	Bologna
Italy	Azienda Ospedaliera di Rilievo Nazionale Monaldi - Cotugno-CTO Cardiologia S.U.N.	Naples
Italy	Azienda Ospedaliera di Rilievo Nazionale Monaldi - Cotugno-CTO Cardiologia S.U.N.	Napoli
Italy	Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche	Rome
Mexico	Instituto Nacional de Cardiologia	Mexico City
Mexico	Hospital Universitario de la UANL	Monterrey
Mexico	Unidad de Investigacion Clinica en Medicina S.C.	Monterrey
Netherlands	Radboud University Nijmegen Medical Center	Amsterdam
Netherlands	VU Medish Centrum	Amsterdam
Poland	Klinika Chorób Serca i Naczyn, Krakowski Szpital Specjalistyczny im. Jana Pawla II	Kraków
Poland	Europejskie Centrum Zdrowia Otwock	Warsaw
Poland	Oddzial Kardiologiczny	Wroclaw
Portugal	Servico de Cardiologia Hospital de Santa Marta	Lisbon
Puerto Rico	Auxilio Mutuo Hospital CardioPulmonary Research Center	Guaynabo
Spain	Hospital Clínic I Provincial	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Sweden	Skane University Hospital	Lund
United Kingdom	Papworth Hospital	Cambridge
United Kingdom	Papworth Hospital NHS Foundation Trust	Glasgow
United Kingdom	Royal Free Hospital	London
United Kingdom	Freeman Hospital	Newcastle
United Kingdom	Royal Hallamshire Hospital	Sheffield
United States	Alexandria Cardiology Clinic	Alexandria	Louisiana
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	The Emory Clinic	Atlanta	Georgia
United States	The Children's Hospital	Aurora	Colorado
United States	University of Colorado Health Science Center	Aurora	Colorado
United States	Johns Hopkins Outpatient Center	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	The Kirklin Clinic	Birmingham	Alabama
United States	Brigham and Woman's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of North Carolina Hospitals	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	The University of Chicago Hospitals	Chicago	Illinois
United States	The Carl and Ethyl Linder Center for Research and Education at the Christ Church	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	University of California, San Francisco-Fresno	Fresno	California
United States	Baylor College of Medicine	Houston	Texas
United States	University of Texas Medical School	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Florida College of Medicine Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	West Los Angeles VA Healthcare Center	Los Angeles	California
United States	Kentuckiana Pulmonary Associates	Louisville	Kentucky
United States	Aurora Cardiovascular Services	Milwaukee	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	University of Minnesota Medical Center, Fairview	Minneapolis	Minnesota
United States	Intermountain Medical Center	Murray	Utah
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University 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	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists, Ltd.	Phoenix	Arizona
United States	Mayo Clinic Phoenix	Phoenix	Arizona
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	Legacy Pulmonary Clinic	Portland	Oregon
United States	Maine Medical Center	Portland	Maine
United States	Oregon Health and Sciences University	Portland	Oregon
United States	Mary Parkes Center	Rochester	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	UC Davis Medical Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	The University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSD Medical Center	San Diego	California
United States	University of California San Francisco Medical Center	San Francisco	California
United States	University of Washington Medical Center	Seattle	Washington
United States	Stanford University, Pulmonary and Critical Care Medicine	Stanford	California
United States	The University of Toledo Medical Center	Toledo	Ohio
United States	Harbor-UCLA Medical Center	Torrance	California
United States	University Medical Center	Tucson	Arizona
United States	University of Arizona Clinical and Translational Science (CATS) Research Center	Tucson	Arizona
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
United Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  France,  Germany,  India,  Ireland,  Israel,  Italy,  Mexico,  Netherlands,  Poland,  Portugal,  Puerto Rico,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Exercise Capacity at Month 12	Assess the effect of continued therapy with oral treprostinil on exercise capacity as assessed by the change from Baseline in 6-Minute Walk Test (6MWT) after 1 year of treatment. The 6MWT is the clinical standard for assessing subject functional status in the treatment of PAH and has been considered an objective measure of subject functional status by the American Thoracic Society. The distance a subject can walk in 6 minutes is recorded in meters.	From First Visit (Visit 1) to Month 12