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

NCT ID: NCT01027949

Last Updated: 2021-05-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

894 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-16

Study Completion Date

2020-02-12

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Pulmonary Arterial Hypertension

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Oral Treprostinil

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

Group Type EXPERIMENTAL

Oral Treprostinil

Intervention Type DRUG

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

Interventions

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Oral Treprostinil

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

Intervention Type DRUG

Other Intervention Names

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Treprostinil diethanolamine, treprostinil diolamine UT-15C

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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United Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The Kirklin Clinic

Birmingham, Alabama, United States

Site Status

Arizona Pulmonary Specialists, Ltd.

Phoenix, Arizona, United States

Site Status

Mayo Clinic Phoenix

Phoenix, Arizona, United States

Site Status

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Site Status

University Medical Center

Tucson, Arizona, United States

Site Status

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

Tucson, Arizona, United States

Site Status

University of California, San Francisco-Fresno

Fresno, California, United States

Site Status

West Los Angeles VA Healthcare Center

Los Angeles, California, United States

Site Status

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Site Status

UC Davis Medical Center

Sacramento, California, United States

Site Status

UCSD Medical Center

San Diego, California, United States

Site Status

University of California San Francisco Medical Center

San Francisco, California, United States

Site Status

Stanford University, Pulmonary and Critical Care Medicine

Stanford, California, United States

Site Status

Harbor-UCLA Medical Center

Torrance, California, United States

Site Status

The Children's Hospital

Aurora, Colorado, United States

Site Status

University of Colorado Health Science Center

Aurora, Colorado, United States

Site Status

University of Florida College of Medicine Jacksonville

Jacksonville, Florida, United States

Site Status

Cleveland Clinic Florida

Weston, Florida, United States

Site Status

The Emory Clinic

Atlanta, Georgia, United States

Site Status

The University of Chicago Hospitals

Chicago, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Kentuckiana Pulmonary Associates

Louisville, Kentucky, United States

Site Status

Alexandria Cardiology Clinic

Alexandria, Louisiana, United States

Site Status

Maine Medical Center

Portland, Maine, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Johns Hopkins Outpatient Center

Baltimore, Maryland, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Brigham and Woman's Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

Winthrop University Hospital

Mineola, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Mary Parkes Center

Rochester, New York, United States

Site Status

University of North Carolina Hospitals

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

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

Cincinnati, Ohio, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

University Hospitals of Cleveland

Cleveland, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

The University of Toledo Medical Center

Toledo, Ohio, United States

Site Status

Legacy Pulmonary Clinic

Portland, Oregon, United States

Site Status

Oregon Health and Sciences University

Portland, Oregon, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

University of Texas Medical School

Houston, Texas, United States

Site Status

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Aurora Cardiovascular Services

Milwaukee, Wisconsin, United States

Site Status

The Prince Charles Hospital

Chermside West, , Australia

Site Status

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

Darlinghurst, , Australia

Site Status

The Alfred Hospital

Melbourne, , Australia

Site Status

Royal Perth Hospital

Perth, , Australia

Site Status

Medizininische Universitaet Wien

Vienna, , Austria

Site Status

Universitaetsklinik für Innere Medizin Innsbruck

Vienna, , Austria

Site Status

Medical University Graz

Wein, , Austria

Site Status

Department of Cardiology Erasme University Hospital

Brussels, , Belgium

Site Status

University Hospital Gasthuisberg

Leuven, , Belgium

Site Status

Peter Lougheed Centre

Calgary, Alberta, Canada

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Vancouver Coastal Health Authority Vancouver General Hospital

Vancouver, British Columbia, Canada

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

London Health Sciences Center Victoria Hospital

Toronto, Ontario, Canada

Site Status

Sir Mortimer B. Davis Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Beijing Shijitan Hospital, Cadres Respiratory Department

Beijing, , China

Site Status

Peking Union Medical College Hospital, Respiratory Medicine Department

Beijing, , China

Site Status

Shanghai Pulmonary Hospital, Respiratory Medicine Department

Shanghai, , China

Site Status

Service Chirurgie Thoracique, Hôpital Haut Levêque

Pessac, Pessac Cedex, France

Site Status

PMAC, Clinique de Pneumologie

Bernin, , France

Site Status

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

Brest, , France

Site Status

Hospital Antoine Beclere

Clamart, , France

Site Status

Hospital Claude Huriez

Lille, , France

Site Status

Hôpital Louis Pradel

Lyon, , France

Site Status

CHU Arnaud de Villeneuve - Service maladies respiratoires

Montpellier, , France

Site Status

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

Toulouse, , France

Site Status

Universitätsklinikum Dresden Abtl. Pneumologie

Dresden, , Germany

Site Status

University Hospital Greifswald

Greifswald, , Germany

Site Status

DRK Kliniken Berlin Köpenick

Hamburg, , Germany

Site Status

Universitatsklinikum Hamburg Eppendorf

Hamburg, , Germany

Site Status

Universitätsklinkium Köln Klinik III für Innere Medizin

Hamburg, , Germany

Site Status

Zentrum für Lungenhochdruck Thoraxklinik am Universitätsklinikum Heidelberg

Hamburg, , Germany

Site Status

Medizinische Hochschule Hannover (MHH)

Hanover, , Germany

Site Status

Dept. of Internal Medicine III University Heidelberg

Heidelberg, , Germany

Site Status

Care Institute of Medical Sciences

Ahmedabad, Gujarat, India

Site Status

Narayana Hrudayalaya Hospitals

Bangalore, Karnataka, India

Site Status

Asian Heart Institute & Research Centre Pvt. Ltd.

Mumbai, Maharashtra, India

Site Status

Poona Hospital and Research Centre

Pune, Maharashtra, India

Site Status

Life Care Institute of Medical Sciences & Research

Ahmedabad, , India

Site Status

Sri Ramachandra Medical College & Research Institute

Chennai, , India

Site Status

G. Kuppuswamy Naidu Memorial Hospital

Coimbatore, , India

Site Status

PRIME Hospitals

Hyderabad, , India

Site Status

Sir Ganga Ram Hospital

New Delhi, , India

Site Status

Ruby Hall Clinic

Pune, , India

Site Status

Queen's NRI Hospital

Visakhapatnam, , India

Site Status

Pulmonary Hypertension Unit Centre for Lung Health Mater Misericordiae University Hospital

Dublin, , Ireland

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

The Lady Davis Carmel Medical Center

Haifa, , Israel

Site Status

Hadassah Hebrew University Medical Center

Jerusalem, , Israel

Site Status

Pulmonary Institute Rabin Medical Center (Belinson Kampus)

Petah Tikva, , Israel

Site Status

Pulmonary Institute Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Policlinico S. Orsola Malpighi - Università degli studi di Bologna

Bologna, , Italy

Site Status

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

Naples, , Italy

Site Status

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

Napoli, , Italy

Site Status

Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche

Rome, , Italy

Site Status

Instituto Nacional de Cardiologia

Mexico City, , Mexico

Site Status

Hospital Universitario de la UANL

Monterrey, , Mexico

Site Status

Unidad de Investigacion Clinica en Medicina S.C.

Monterrey, , Mexico

Site Status

Radboud University Nijmegen Medical Center

Amsterdam, , Netherlands

Site Status

VU Medish Centrum

Amsterdam, , Netherlands

Site Status

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

Krakow, , Poland

Site Status

Europejskie Centrum Zdrowia Otwock

Warsaw, , Poland

Site Status

Oddzial Kardiologiczny

Wroclaw, , Poland

Site Status

Servico de Cardiologia Hospital de Santa Marta

Lisbon, , Portugal

Site Status

Auxilio Mutuo Hospital CardioPulmonary Research Center

Guaynabo, , Puerto Rico

Site Status

Hospital Clínic I Provincial

Barcelona, , Spain

Site Status

Hospital Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital 12 de Octubre

Madrid, , Spain

Site Status

Skane University Hospital

Lund, , Sweden

Site Status

Papworth Hospital

Cambridge, , United Kingdom

Site Status

Papworth Hospital NHS Foundation Trust

Glasgow, , United Kingdom

Site Status

Royal Free Hospital

London, , United Kingdom

Site Status

Freeman Hospital

Newcastle, , United Kingdom

Site Status

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Site Status

Countries

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

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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TDE-PH-304

Identifier Type: -

Identifier Source: org_study_id

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