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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03496623
Other study ID # RIN-PH-304
Secondary ID
Status Terminated
Phase Phase 3
First received
Last updated
Start date May 8, 2018
Est. completion date October 13, 2022

Study information

Verified date November 2023
Source United Therapeutics
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary objective of this study is to demonstrate the efficacy of inhaled treprostinil compared to placebo in improving exercise ability as measured by change from baseline in 6-Minute Walk Distance (6MWD) following 12 weeks of active treatment in participants with PH-COPD.


Description:

This is a multicenter, randomized, double-blind, placebo-controlled, 34-week, cross-over study, with a Treatment Period of approximately 26 weeks under the Original Crossover Design or, if applicable, a 21-week parallel study, with a Treatment Period of approximately 14 weeks under the Contingent Parallel Design.


Recruitment information / eligibility

Status Terminated
Enrollment 188
Est. completion date October 13, 2022
Est. primary completion date October 13, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: Participants who meet the following criteria may be included in the study: 1. Participant voluntarily gives informed consent to participate in the study. 2. Males and females 18 years of age and above at the time of informed consent. 1. Women of childbearing potential (defined as less than 1 year post-menopausal and not surgically sterile) must agree to practice abstinence or use 2 highly effective methods of contraception (defined as a method of birth control that results in a low failure rate, [<1% per year], such as approved hormonal contraceptives, barrier methods [such as condom or diaphragm] used with a spermicide, or an intrauterine device) for the duration of study treatment and for 48 hours after discontinuing study drug. Participants must have a negative pregnancy test at the Screening Visit 1 (urine [prior to the first dose of study medication] and serum) and Baseline Visit (Study Week 1) (urine). 2. Males with a partner of childbearing potential must agree to use a barrier method (condom) with a spermicide for the duration of treatment and for at least 48 hours after discontinuing study drug. 3. Diagnosis of PH-COPD (World Heath Organization [WHO] Group 3). 4. Clinical diagnosis of COPD will be made using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) diagnostic criteria (GOLD Criteria 2020) and spirometry with the following documented parameters measured during Screening Visit 1 (prior to start of low-dose inhaled treprostinil): 1. Forced expiratory volume in 1 second (FEV1) <80% predicted 2. FEV1/Forced vital capacity (FVC) <70 5. The participant has a resting saturation peripheral capillary oxygenation (SpO2) greater than or equal to 90%, with or without supplemental oxygen, but not to exceed 10 liters (L)/min oxygen supplementation by any mode of delivery during Screening Visit 1. 6. During Screening Visit 1 prior to start of low-dose inhaled treprostinil, a 6MWD greater than or equal to 100 meters. 7. Have a right heart catheterization (RHC) performed during Screening Visit 1. (A previous RHC obtained within 12 months prior to the start of Screening Visit 1 is acceptable for determining eligibility, even if done without oxygen or vasodilator challenge, and a repeat RHC is not required.) The following parameters must be documented for eligibility: 1. Pulmonary vascular resistance (PVR) greater than or equal to 4 Wood units 2. A pulmonary artery wedge pressure (PAWP) or left ventricular end-diastolic pressure (LVEDP) of less than or equal to 15 millimeters of mercury (mmHg) 3. A Pulmonary artery pressure mean (PAPm) of greater than or equal to 30 mmHg 8. Participants must be on a stable and optimized dose of chronic COPD medications for greater than or equal to 30 days prior to start of Screening Visit 1 and remain on the same dose throughout the Screening Period. 9. In the opinion of the Investigator, the participant can communicate effectively with study personnel and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits. Exclusion Criteria: The following will exclude participants from the study: 1. The participant has a diagnosis of either pulmonary arterial hypertension (PAH) or pulmonary hypertension (PH) due to reasons other than COPD. This would include, but is not limited to, chronic thromboembolic PH or acute/recent deep vein thrombosis or pulmonary embolism, untreated or inadequately treated obstructive sleep apnea, connective tissue disease (including but not limited to systemic sclerosis/scleroderma or systemic lupus erythematosus), sarcoidosis, human immunodeficiency virus-1 infection, and other conditions under WHO Group 1, 2, 4, and 5 classifications. 2. Based on chest computed tomography (CT) imaging during Screening Visit 1, the participant has a confirmed diagnosis of WHO Group 3 PH, other than COPD, such as idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, diffuse parenchymal lung disease or interstitial lung disease. A previous chest CT scan performed within the 6 months prior to the start of Screening Visit 1 is also acceptable, and a repeat assessment is not required. A redacted CT scan report (from Screening Visit 1 or dated within prior 6 months) should be provided to the Medical Monitor with the Pre-Baseline Review Form to confirm eligibility. 3. The participant has received any Food and Drug Administration (FDA)-approved medication for the treatment of PAH (that is, prostacyclin, prostacyclin receptor agonist, endothelin receptor antagonist [ERA], phosphodiesterase type 5 inhibitor [PDE5-I], or soluble guanylate cyclase [sGC] stimulator) at Screening Visit 1 and thereafter, except if received for acute vasoreactivity testing. 4. The participant has a previous diagnosis of homozygous alpha-1 antitrypsin deficiency. 5. The participant has any prior intolerance to inhaled prostanoid therapy. 6. Inability to tolerate low-dose (3 breaths, 18 mcg) study drug and/or inability to follow dosing regimen during the Screening Period (pre-randomization). 7. Unwilling or unable to use Sponsor-provided devices (actigraph, spirometer, or smart device). 8. The participant has evidence of clinically significant left-sided heart disease (including but not limited to left ventricular ejection fraction <40%, left ventricular hypertrophy,) or clinically significant cardiologic conditions, such as congestive heart failure, coronary artery disease, or valvular heart disease. Note: Participants with abnormal left ventricular function attributable to the effects of right ventricular overload will not be excluded, but a discussion with and approval by the Sponsor Medical Monitor is needed. 9. Any exacerbation of COPD (including hospitalization or outpatient therapy) or active pulmonary or upper respiratory infection 60 days prior to start of Screening Visit 1 through the Baseline Visit. This is defined as worsening of respiratory symptoms that required treatment with corticosteroids and/or antibiotics. 10. Initiation of pulmonary rehabilitation within 12 weeks prior to start of Screening Visit 1 or, in the opinion of the Investigator, pulmonary rehabilitation is likely to be needed during the study Treatment Period. 11. The participant has any form of congenital heart disease (repaired or unrepaired; other than a patent foramen ovale). 12. The participant has any musculoskeletal disorder (severe arthritis of the lower limbs which limits ambulation, recent hip or knee joint replacement, artificial leg) or any other condition that would likely be the primary limitation to ambulation. 13. Use of any other investigational drug or device within 30 days prior to the start of Screening Visit 1. 14. Any other clinically significant illness or abnormal laboratory value(s) measured during the Screening Period that, in the opinion of the Investigator, might adversely affect the interpretation of the study data or safety of the participant.

Study Design


Intervention

Drug:
Inhaled treprostinil solution
Treprostinil inhalation solution
Placebo solution
Placebo solution

Locations

Country Name City State
Argentina El Cruce Hospital Buenos Aires
Argentina Hospital Britanico de Buenos Aires Buenos Aires
Argentina Fundacion Favaloro Ciudad Autonoma Buenos Aires
Argentina Hospital Italiano de Buenos Aires Ciudad Autonoma Buenos Aires
Argentina Hospital Italiano de Cordoba Cordoba
Argentina Centro Medico 21 de Diciembre Santa Fe
Israel Lady Davis Carmel Medical Centre Haifa
Israel Hadassah-Hebrew University Hospital Jerusalem
Israel Rabin Medical Center Petah Tiva
Israel The Chaim Sheba Medical Center Tel Hashomer
Puerto Rico CardioPulmonary Research Center Guaynabo
United States Albany Medical College Albany New York
United States The University of New Mexico Albuquerque New Mexico
United States Pulmonary & Critical Care of Atlanta Atlanta Georgia
United States University of Colorado Health Sciences Center Aurora Colorado
United States Georgia Clinical Research Austell Georgia
United States University of Maryland Medical Center Baltimore Maryland
United States The University of Alabama at Birmingham Birmingham Alabama
United States Brigham and Women's Hospital Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States University of North Carolina at Chapel Hill Chapel Hill North Carolina
United States Medical University of South Carolina Charleston South Carolina
United States University of Illinois Medical Center Chicago Illinois
United States The Carl and Edyth Lindner Research Center at the Christ Hospital Cincinnati Ohio
United States University of Cincinnati Cincinnati Ohio
United States St. Francis Medical Institute Clearwater Florida
United States Cleveland Clinic Cleveland Ohio
United States The Ohio State University Wexner Medical Center Columbus Ohio
United States UT Southwestern Medical Center Dallas Texas
United States Detroit Medical Center Lung Institute Detroit Michigan
United States Henry Ford Health System Detroit Michigan
United States Clinical Research Associates of Central PA, LLC DuBois Pennsylvania
United States Duke University Medical Center Durham North Carolina
United States Texas Tech El Paso Texas
United States Advocate Aurora Health Care Elmhurst Illinois
United States Inova Fairfax Hospital Falls Church Virginia
United States University of Florida Clinical Research Center Gainesville Florida
United States Spectrum Health Grand Rapids Michigan
United States Hartford Hospital Hartford Connecticut
United States Indiana University Healh North Hospital Indianapolis Indiana
United States St. Vincent Medical Group, Inc. Indianapolis Indiana
United States Mayo Clinic - Jacksonville Jacksonville Florida
United States St. Vincent's Lung, Sleep, and Critical Care Specialists Jacksonville Florida
United States Pulmonary Disease Specialists Kissimmee Florida
United States Statcare Pulmonary Consultants Knoxville Tennessee
United States University of Kentucky Medical Center Lexington Kentucky
United States Advocate Condell Medical Center Libertyville Illinois
United States South Denver Cardiology Littleton Colorado
United States Loma Linda University Medical Center Loma Linda California
United States Cedars-Sinai Medical Center Los Angeles California
United States University of Southern California Los Angeles California
United States West Los Angeles VA Healthcare Center Los Angeles California
United States Kentuckiana Pulmonary Associates Louisville Kentucky
United States University of Louisville Research Foundation Louisville Kentucky
United States University of Wisconsin School of Medicine and Public Health Madison Wisconsin
United States University of Miami Hospital Miami Florida
United States Medical College of Wisconsin Milwaukee Wisconsin
United States University of Minnesota Minneapolis Minnesota
United States The Mount Sinai Hospital New York New York
United States Advocate Heart Institute & Pulmonology Normal Illinois
United States Edward Heart Hospital Oakbrook Terrace Illinois
United States Temple Lung Center Philadelphia Pennsylvania
United States Banner University Medical Center Phoenix Arizona
United States Allegheny General Hospital Pittsburgh Pennsylvania
United States University of Pittsburgh Medical Center - Montefiore Pittsburgh Pennsylvania
United States Rhode Island Hospital Providence Rhode Island
United States Pulmonary Associates of Richmond, Inc. Richmond Virginia
United States Carilion Clinic Roanoke Virginia
United States University of Rochester Medical Center Rochester New York
United States University of California Davis Medical Center Sacramento California
United States Santa Barbara Pulmonary Associates Santa Barbara California
United States University of South Florida Tampa Florida
United States Beaumont Health Troy Michigan
United States University of Arizona Clinical and Translational Science (CATS) Research Center Tucson Arizona
United States MedStar Washington Hospital Center Washington District of Columbia
United States Clear Lake Specialties/Tranquility Research Webster Texas

Sponsors (1)

Lead Sponsor Collaborator
United Therapeutics

Countries where clinical trial is conducted

United States,  Argentina,  Israel,  Puerto Rico, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change From Baseline to Week 12 in 6-Minute Walk Distance (6MWD) 6 MWD was calculated at peak exposure (10 to 60 minutes after dosing). 6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course for 6 minutes (timed) and the distance walked (in meters) was recorded. Statistical analyses were not performed due to lack of appropriate sample size. Baseline, Week 12
Secondary Change From Baseline to Week 12 in Moderate to Vigorous Physical Activity (MVPA) MVPA was defined as the number of minutes spent in moderate to vigorous physical activity as measured via a wrist-worn medical grade physical activity monitor. The screening data were used to establish a baseline level of physical activity. Baseline, Week 12
Secondary Change From Baseline to Week 12 in Overall Activity Overall activity was defined as the number of minutes spent in overall activity (non-sedentary activity) as measured via a wrist-worn medical grade physical activity monitor. The screening data will be used to establish a baseline level of physical activity. Baseline, Week 12
Secondary Change From Baseline to Week 12 in Borg Dyspnea Score The Borg Dyspnea Score was a 11-point scale rating the maximum level of dyspnea experienced during the 6-minute walking test (6MWT). Scores range from 0 (no dyspnea at all) to 10 (very, very severe dyspnea), with lower scores indicating a less exertion (a better outcome). The Borg Dyspnea Score was to be evaluated immediately after the 6MWT. Baseline, Week 12
Secondary Change From Baseline to Week 12 in 6MWD/Borg Dyspnea Composite Score 6MWD was calculated at peak exposure (10 to 60 minutes after dosing). 6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course for 6 minutes (timed) and the distance walked (in meters) was recorded. The Borg Dyspnea Score was an 11-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (no dyspnea at all) to 10 (very, very severe dyspnea), with lower scores indicating less exertion (a better outcome). The Borg Dyspnea Score was to be evaluated immediately after the 6MWT. The average 6WMWD data and the average Borg Dyspnea Composite Score data were summed and reported as the composite score. Baseline, Week 12
Secondary Change From Baseline to Week 12 in Quality of Life (QOL) Measured by St. George's Respiratory Questionnaire (SGRQ) The SGRQ is a designed to measure how breathing impacts overall health, daily life, and perceived well-being in participants with obstructive airways disease. Scores range from 0 to 100, with lower scores indicating a better QoL. Baseline, Week 12
Secondary Change From Baseline to Week 12 in QOL Measured by the University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) The UCSD SOBQ is a self-administered rating of dyspnea associated with activities of daily living. The questionnaire uses a 6-point scale where 0 = "not at all" and 5 = "maximal or unable to do because of breathlessness". Lower scores indicate a better QoL. Baseline, Week 12
Secondary Change From Baseline to Week 12 in Plasma Concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Levels The NT-proBNP concentration is a biomarker associated with changes in right heart morphology and function. Improvement is defined as a decrease in the NT-proBNP plasma concentration. Baseline, Week 12
Secondary Change From Baseline to Week 12 in Patient Global Assessment (PGA) The PGA is used to rate participant fatigue and shortness of breath. Participants will use the Sponsor-provided smart device for at-home capture of PGA data. The PGA used a 5-point response scale of: "never," "rarely," "sometimes," "often," or "always" with higher scores indicating a worse symptom rating. Baseline, Week 12
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