A Phase 3 Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Participants With Pulmonary Hypertension (PH) Due to Chronic Obstructive Pulmonary Disease (COPD)

Phase 3

Terminated

Conditions: Pulmonary Hypertension
Chronic Obstructive Pulmonary Disease

Interventions: Drug: Inhaled treprostinil solution
Drug: Placebo solution

Registration Number: NCT03496623

Lead Sponsor: United Therapeutics

Brief 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.

Detailed 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 & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 188

Inclusion Criteria

Participants who meet the following criteria may be included in the study:

Participant voluntarily gives informed consent to participate in the study.
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.
Diagnosis of PH-COPD (World Heath Organization [WHO] Group 3).
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
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.
During Screening Visit 1 prior to start of low-dose inhaled treprostinil, a 6MWD greater than or equal to 100 meters.
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
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.
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:

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.
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.
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.
The participant has a previous diagnosis of homozygous alpha-1 antitrypsin deficiency.
The participant has any prior intolerance to inhaled prostanoid therapy.
Inability to tolerate low-dose (3 breaths, 18 mcg) study drug and/or inability to follow dosing regimen during the Screening Period (pre-randomization).
Unwilling or unable to use Sponsor-provided devices (actigraph, spirometer, or smart device).
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.
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.
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.
The participant has any form of congenital heart disease (repaired or unrepaired; other than a patent foramen ovale).
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.
Use of any other investigational drug or device within 30 days prior to the start of Screening Visit 1.
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 Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Inhaled Treprostinil	Inhaled treprostinil solution	Inhaled treprostinil delivered via an ultrasonic nebulizer with a target dosing regimen of 12 breaths (72 micrograms \[mcg\]) 4 times daily (QID)
Placebo	Placebo solution	Placebo delivered via an ultrasonic nebulizer for QID administration

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 12 in 6-Minute Walk Distance (6MWD)	Baseline, Week 12	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Week 12 in Moderate to Vigorous Physical Activity (MVPA)	Baseline, Week 12	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.
Change From Baseline to Week 12 in Overall Activity	Baseline, Week 12	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.
Change From Baseline to Week 12 in Borg Dyspnea Score	Baseline, Week 12	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.
Change From Baseline to Week 12 in 6MWD/Borg Dyspnea Composite Score	Baseline, Week 12	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.
Change From Baseline to Week 12 in Quality of Life (QOL) Measured by St. George's Respiratory Questionnaire (SGRQ)	Baseline, Week 12	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.
Change From Baseline to Week 12 in QOL Measured by the University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ)	Baseline, Week 12	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.
Change From Baseline to Week 12 in Plasma Concentration of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Levels	Baseline, Week 12	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.
Change From Baseline to Week 12 in Patient Global Assessment (PGA)	Baseline, Week 12	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.

Trial Locations

Locations (76): University of Southern California
🇺🇸
Los Angeles, California, United States
Pulmonary & Critical Care of Atlanta
🇺🇸
Atlanta, Georgia, United States
St. Vincent Medical Group, Inc.
🇺🇸
Indianapolis, Indiana, United States
Hartford Hospital
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Hartford, Connecticut, United States
St. Francis Medical Institute
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Clearwater, Florida, United States
South Denver Cardiology
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Littleton, Colorado, United States
MedStar Washington Hospital Center
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Washington, District of Columbia, United States
Mayo Clinic - Jacksonville
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Jacksonville, Florida, United States
University of Maryland Medical Center
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Baltimore, Maryland, United States
Cleveland Clinic
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Cleveland, Ohio, United States
Pulmonary Disease Specialists
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Kissimmee, Florida, United States
Texas Tech
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El Paso, Texas, United States
Allegheny General Hospital
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Pittsburgh, Pennsylvania, United States
Brigham and Women's Hospital
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Boston, Massachusetts, United States
Indiana University Healh North Hospital
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Indianapolis, Indiana, United States
Statcare Pulmonary Consultants
🇺🇸
Knoxville, Tennessee, United States
St. Vincent's Lung, Sleep, and Critical Care Specialists
🇺🇸
Jacksonville, Florida, United States
Temple Lung Center
🇺🇸
Philadelphia, Pennsylvania, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States
University of Miami Hospital
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Miami, Florida, United States
The University of New Mexico
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Albuquerque, New Mexico, United States
Spectrum Health
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Grand Rapids, Michigan, United States
The Mount Sinai Hospital
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New York, New York, United States
UT Southwestern Medical Center
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Dallas, Texas, United States
Centro Medico 21 de Diciembre
🇦🇷
Santa Fe, Argentina
Banner University Medical Center
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Phoenix, Arizona, United States
Detroit Medical Center Lung Institute
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Detroit, Michigan, United States
Henry Ford Health System
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Detroit, Michigan, United States
Duke University Medical Center
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Durham, North Carolina, United States
The Carl and Edyth Lindner Research Center at the Christ Hospital
🇺🇸
Cincinnati, Ohio, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Medical College of Wisconsin
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Milwaukee, Wisconsin, United States
University of Rochester Medical Center
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Rochester, New York, United States
University of Colorado Health Sciences Center
🇺🇸
Aurora, Colorado, United States
Santa Barbara Pulmonary Associates
🇺🇸
Santa Barbara, California, United States
The University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
University of Arizona Clinical and Translational Science (CATS) Research Center
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Tucson, Arizona, United States
Cedars-Sinai Medical Center
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Los Angeles, California, United States
Loma Linda University Medical Center
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Loma Linda, California, United States
University of Florida Clinical Research Center
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Gainesville, Florida, United States
West Los Angeles VA Healthcare Center
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Los Angeles, California, United States
Georgia Clinical Research
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Austell, Georgia, United States
University of Illinois Medical Center
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Chicago, Illinois, United States
Advocate Aurora Health Care
🇺🇸
Elmhurst, Illinois, United States
Edward Heart Hospital
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Oakbrook Terrace, Illinois, United States
Advocate Heart Institute & Pulmonology
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Normal, Illinois, United States
University of Kentucky Medical Center
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Lexington, Kentucky, United States
Beaumont Health
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Troy, Michigan, United States
Albany Medical College
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Albany, New York, United States
The Ohio State University Wexner Medical Center
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Columbus, Ohio, United States
Clinical Research Associates of Central PA, LLC
🇺🇸
DuBois, Pennsylvania, United States
University of Pittsburgh Medical Center - Montefiore
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Pittsburgh, Pennsylvania, United States
Inova Fairfax Hospital
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Falls Church, Virginia, United States
University of Wisconsin School of Medicine and Public Health
🇺🇸
Madison, Wisconsin, United States
Hospital Britanico de Buenos Aires
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Buenos Aires, Argentina
El Cruce Hospital
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Buenos Aires, Argentina
Fundacion Favaloro
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Ciudad Autonoma Buenos Aires, Argentina
Hospital Italiano de Buenos Aires
🇦🇷
Ciudad Autonoma Buenos Aires, Argentina
Hospital Italiano de Cordoba
🇦🇷
Cordoba, Argentina
Rabin Medical Center
🇮🇱
Petah Tiva, Israel
Hadassah-Hebrew University Hospital
🇮🇱
Jerusalem, Israel
Lady Davis Carmel Medical Centre
🇮🇱
Haifa, Israel
The Chaim Sheba Medical Center
🇮🇱
Tel Hashomer, Israel
CardioPulmonary Research Center
🇵🇷
Guaynabo, Puerto Rico
Advocate Condell Medical Center
🇺🇸
Libertyville, Illinois, United States
Clear Lake Specialties/Tranquility Research
🇺🇸
Webster, Texas, United States
Carilion Clinic
🇺🇸
Roanoke, Virginia, United States
University of Minnesota
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Minneapolis, Minnesota, United States
University of South Florida
🇺🇸
Tampa, Florida, United States
University of California Davis Medical Center
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Sacramento, California, United States
Kentuckiana Pulmonary Associates
🇺🇸
Louisville, Kentucky, United States
University of Louisville Research Foundation
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Louisville, Kentucky, United States
University of North Carolina at Chapel Hill
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Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Pulmonary Associates of Richmond, Inc.
🇺🇸
Richmond, Virginia, United States
Rhode Island Hospital
🇺🇸
Providence, Rhode Island, United States

A Phase 3 Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Participants With Pulmonary Hypertension (PH) Due to Chronic Obstructive Pulmonary Disease (COPD)

Recruitment & Eligibility

Study & Design

Trial Locations

Instant Trial Alerts

Instant Trial Alerts