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

NCT01027949 | Completed Phase 3 Results

• 1 other identifier: TDE-PH-304
• Study Type: interventional
• Target: 894
• Locations: 19 countries
• Sites: 131

Brief 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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Oral Treprostinil

EXPERIMENTAL

Subjects from previous studies TDE-PH-202 (NCT01104870), TDE-PH-203 (NCT01477333), and TDE-PH-205 (NCT01588405), TDE-PH-301 (NCT00325442), TDE-PH-302 (NCT00325403), or TDE PH-308 (NCT00887978). Subjects were instructed to take the appropriate amount of 0.125, 0.25, 0.5, 1, and/or 2.5 mg tablets based upon their prescribed dose. Investigators were instructed to increase the dose of oral treprostinil in the absence of dose limiting drug-related AEs to ensure each subject received the optimal clinical dose throughout the study

Drug: Oral Treprostinil

Interventions

Oral Treprostinil DRUG

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

Also known as: Treprostinil diethanolamine, treprostinil diolamine, UT-15C

Oral Treprostinil

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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).
• 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.
• 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.
• 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.

Sponsors & Collaborators

• United Therapeutics: lead

Study Sites (135)

The Kirklin Clinic

Birmingham, Alabama, 35233, United States

Location

Arizona Pulmonary Specialists, Ltd.

Phoenix, Arizona, 85013, United States

Location

Mayo Clinic Phoenix

Phoenix, Arizona, 85054, United States

Location

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Location

University Medical Center

Tucson, Arizona, 85724, United States

Location

University of Arizona Clinical and Translational Science (CATS) Research Center

Tucson, Arizona, 85724, United States

Location

University of California, San Francisco-Fresno

Fresno, California, 93701, United States

Location

West Los Angeles VA Healthcare Center

Los Angeles, California, 90073, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

UCSD Medical Center

San Diego, California, 30322, United States

Location

University of California San Francisco Medical Center

San Francisco, California, 94118, United States

Location

Stanford University, Pulmonary and Critical Care Medicine

Stanford, California, 94305-5351, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

University of Colorado Health Science Center

Aurora, Colorado, 80045, United States

Location

University of Florida College of Medicine Jacksonville

Jacksonville, Florida, 32209, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

The University of Chicago Hospitals

Chicago, Illinois, 60637, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Kentuckiana Pulmonary Associates

Louisville, Kentucky, 40202, United States

Location

Alexandria Cardiology Clinic

Alexandria, Louisiana, 71301, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Outpatient Center

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Brigham and Woman's Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48103, United States

Location

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110-1093, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-5300, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Mary Parkes Center

Rochester, New York, 14643, United States

Location

University of North Carolina Hospitals

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Carl and Ethyl Linder Center for Research and Education at the Christ Church

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267-0564, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

The University of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

Legacy Pulmonary Clinic

Portland, Oregon, 97210, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-2650, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Medical School

Houston, Texas, 77030, United States

Location

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Intermountain Medical Center

Murray, Utah, 84157-7000, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Aurora Cardiovascular Services

Milwaukee, Wisconsin, 53215, United States

Location

The Prince Charles Hospital

Chermside West, 4032, Australia

Location

Heart/Lung Transplant Unit - St. Vincent's Hospital

Darlinghurst, 2010, Australia

Location

The Alfred Hospital

Melbourne, 3004, Australia

Location

Royal Perth Hospital

Perth, Australia

Location

Medizininische Universitaet Wien

Vienna, Austria

Location

Universitaetsklinik für Innere Medizin Innsbruck

Vienna, Austria

Location

Medical University Graz

Wein, Austria

Location

Department of Cardiology Erasme University Hospital

Brussels, Belgium

Location

University Hospital Gasthuisberg

Leuven, Belgium

Location

Peter Lougheed Centre

Calgary, Alberta, T1Y 6J4, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Vancouver Coastal Health Authority Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

London Health Sciences Center Victoria Hospital

Toronto, Ontario, N6A 4G5, Canada

Location

Sir Mortimer B. Davis Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Beijing Shijitan Hospital, Cadres Respiratory Department

Beijing, China

Location

Peking Union Medical College Hospital, Respiratory Medicine Department

Beijing, China

Location

Shanghai Pulmonary Hospital, Respiratory Medicine Department

Shanghai, China

Location

Service Chirurgie Thoracique, Hôpital Haut Levêque

Pessac, Pessac Cedex, 33604, France

Location

PMAC, Clinique de Pneumologie

Bernin, France

Location

Centre d'Investigation Clinique Hôpital La Cavale Blanche - CHU Brest

Brest, France

Location

Hospital Antoine Beclere

Clamart, France

Location

Hospital Claude Huriez

Lille, France

Location

Hôpital Louis Pradel

Lyon, France

Location

CHU Arnaud de Villeneuve - Service maladies respiratoires

Montpellier, 34295, France

Location

Service de Pneumologie Centre de Competence pour l'HTAP- Pole des Voies Respiratoires Hôpital Larrey

Toulouse, France

Location

Universitätsklinikum Dresden Abtl. Pneumologie

Dresden, 01307, Germany

Location

University Hospital Greifswald

Greifswald, 17475, Germany

Location

DRK Kliniken Berlin Köpenick

Hamburg, Germany

Location

Universitatsklinikum Hamburg Eppendorf

Hamburg, Germany

Location

Universitätsklinkium Köln Klinik III für Innere Medizin

Hamburg, Germany

Location

Zentrum für Lungenhochdruck Thoraxklinik am Universitätsklinikum Heidelberg

Hamburg, Germany

Location

Medizinische Hochschule Hannover (MHH)

Hanover, Germany

Location

Dept. of Internal Medicine III University Heidelberg

Heidelberg, 69120, Germany

Location

Care Institute of Medical Sciences

Ahmedabad, Gujarat, 380054, India

Location

Narayana Hrudayalaya Hospitals

Bangalore, Karnataka, 560034, India

Location

Asian Heart Institute & Research Centre Pvt. Ltd.

Mumbai, Maharashtra, 400012, India

Location

Poona Hospital and Research Centre

Pune, Maharashtra, 411030, India

Location

Life Care Institute of Medical Sciences & Research

Ahmedabad, 380054, India

Location

Sri Ramachandra Medical College & Research Institute

Chennai, India

Location

G. Kuppuswamy Naidu Memorial Hospital

Coimbatore, India

Location

PRIME Hospitals

Hyderabad, 500038, India

Location

Sir Ganga Ram Hospital

New Delhi, 110060, India

Location

Ruby Hall Clinic

Pune, India

Location

Queen's NRI Hospital

Visakhapatnam, India

Location

Pulmonary Hypertension Unit Centre for Lung Health Mater Misericordiae University Hospital

Dublin, Ireland

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

The Lady Davis Carmel Medical Center

Haifa, Israel

Location

Hadassah Hebrew University Medical Center

Jerusalem, Israel

Location

Pulmonary Institute Rabin Medical Center (Belinson Kampus)

Petah Tikva, Israel

Location

Pulmonary Institute Chaim Sheba Medical Center

Ramat Gan, Israel

Location

Policlinico S. Orsola Malpighi - Università degli studi di Bologna

Bologna, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale Monaldi - Cotugno-CTO Cardiologia S.U.N.

Naples, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale Monaldi - Cotugno-CTO Cardiologia S.U.N.

Napoli, Italy

Location

Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche

Rome, Italy

Location

Instituto Nacional de Cardiologia

Mexico City, 14080, Mexico

Location

Hospital Universitario de la UANL

Monterrey, 64460, Mexico

Location

Unidad de Investigacion Clinica en Medicina S.C.

Monterrey, 64718, Mexico

Location

Radboud University Nijmegen Medical Center

Amsterdam, Netherlands

Location

VU Medish Centrum

Amsterdam, Netherlands

Location

Klinika Chorób Serca i Naczyń, Krakowski Szpital Specjalistyczny im. Jana Pawla II

Krakow, 31-202, Poland

Location

Europejskie Centrum Zdrowia Otwock

Warsaw, Poland

Location

Oddzial Kardiologiczny

Wroclaw, 51-124, Poland

Location

Servico de Cardiologia Hospital de Santa Marta

Lisbon, Portugal

Location

Auxilio Mutuo Hospital CardioPulmonary Research Center

Guaynabo, 00968, Puerto Rico

Location

Hospital Clínic I Provincial

Barcelona, Spain

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Skane University Hospital

Lund, SE 22185, Sweden

Location

Papworth Hospital

Cambridge, United Kingdom

Location

Papworth Hospital NHS Foundation Trust

Glasgow, United Kingdom

Location

Royal Free Hospital

London, United Kingdom

Location

Freeman Hospital

Newcastle, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Louis Holdstock, PhD
• Organization: United Therapeutics

lholdstock@unither.com

919-425-8866

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2009
• First Posted: December 9, 2009
• Study Start: January 16, 2007
• Primary Completion: February 12, 2020
• Study Completion: February 12, 2020
• Last Updated: May 10, 2021
• Results First Posted: May 10, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

ME (3); PR (1); CA (6); IE (1); AU (3); CN (3); PT (1); BE (2); GB (5); US (61); PL (3); FR (8); SE (1); IT (4); IN (11); NL (2); IL (5); ES (3); DE (8)