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)

NCT03496623 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: RIN-PH-304
• Study Type: interventional
• Target: 188
• Locations: 4 countries
• Sites: 76

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.

Conditions

Pulmonary Hypertension; Chronic Obstructive Pulmonary Disease

Keywords

Pulmonary Hypertension; COPD; Inhaled Treprostinil; 6-Minute Walk Test; Tyvaso

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Change From Baseline to Week 12 in Moderate to Vigorous Physical Activity (MVPA)

  Baseline, Week 12

• Change From Baseline to Week 12 in Overall Activity

  Baseline, Week 12

• Change From Baseline to Week 12 in Borg Dyspnea Score

  Baseline, Week 12

• Change From Baseline to Week 12 in 6MWD/Borg Dyspnea Composite Score

  Baseline, Week 12

• Change From Baseline to Week 12 in Quality of Life (QOL) Measured by St. George's Respiratory Questionnaire (SGRQ)

  Baseline, Week 12

Study Arms (2)

Inhaled Treprostinil

EXPERIMENTAL

Inhaled treprostinil delivered via an ultrasonic nebulizer with a target dosing regimen of 12 breaths (72 micrograms \[mcg\]) 4 times daily (QID)

Drug: Inhaled treprostinil solution

Placebo

PLACEBO COMPARATOR

Placebo delivered via an ultrasonic nebulizer for QID administration

Drug: Placebo solution

Interventions

Inhaled treprostinil solution DRUG

Treprostinil inhalation solution

Inhaled Treprostinil

Placebo solution DRUG

Placebo solution

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.
• 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).
• 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):
• Forced expiratory volume in 1 second (FEV1) \<80% predicted
• 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:
• Pulmonary vascular resistance (PVR) greater than or equal to 4 Wood units
• A pulmonary artery wedge pressure (PAWP) or left ventricular end-diastolic pressure (LVEDP) of less than or equal to 15 millimeters of mercury (mmHg)

You may not qualify if:

• 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.

Sponsors & Collaborators

• United Therapeutics: lead

Study Sites (76)

The University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Banner University Medical Center

Phoenix, Arizona, 85006, United States

Location

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

Tucson, Arizona, 85724, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

West Los Angeles VA Healthcare Center

Los Angeles, California, 90073, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

Santa Barbara Pulmonary Associates

Santa Barbara, California, 93102, United States

Location

University of Colorado Health Sciences Center

Aurora, Colorado, 80045, United States

Location

South Denver Cardiology

Littleton, Colorado, 80120, United States

Location

Hartford Hospital

Hartford, Connecticut, 06106, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

St. Francis Medical Institute

Clearwater, Florida, 33765, United States

Location

University of Florida Clinical Research Center

Gainesville, Florida, 32610, United States

Location

St. Vincent's Lung, Sleep, and Critical Care Specialists

Jacksonville, Florida, 32204, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Pulmonary Disease Specialists

Kissimmee, Florida, 34741, United States

Location

University of Miami Hospital

Miami, Florida, 33136, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Pulmonary & Critical Care of Atlanta

Atlanta, Georgia, 30342, United States

Location

Georgia Clinical Research

Austell, Georgia, 30106, United States

Location

University of Illinois Medical Center

Chicago, Illinois, 60612, United States

Location

Advocate Aurora Health Care

Elmhurst, Illinois, 60126, United States

Location

Advocate Condell Medical Center

Libertyville, Illinois, 60048, United States

Location

Advocate Heart Institute & Pulmonology

Normal, Illinois, 06176, United States

Location

Edward Heart Hospital

Oakbrook Terrace, Illinois, 60181, United States

Location

Indiana University Healh North Hospital

Indianapolis, Indiana, 46202, United States

Location

St. Vincent Medical Group, Inc.

Indianapolis, Indiana, 46260, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

Kentuckiana Pulmonary Associates

Louisville, Kentucky, 40202, United States

Location

University of Louisville Research Foundation

Louisville, Kentucky, 40202, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Detroit Medical Center Lung Institute

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Spectrum Health

Grand Rapids, Michigan, 49546, United States

Location

Beaumont Health

Troy, Michigan, 48085, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

The University of New Mexico

Albuquerque, New Mexico, 87106, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

The Mount Sinai Hospital

New York, New York, 10029, United States

Location

University of Rochester Medical Center

Rochester, New York, 14623, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27517, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Carl and Edyth Lindner Research Center at the Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Clinical Research Associates of Central PA, LLC

DuBois, Pennsylvania, 15801, United States

Location

Temple Lung Center

Philadelphia, Pennsylvania, 19140, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh Medical Center - Montefiore

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Statcare Pulmonary Consultants

Knoxville, Tennessee, 37909, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Texas Tech

El Paso, Texas, 79905, United States

Location

Clear Lake Specialties/Tranquility Research

Webster, Texas, 77598, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Pulmonary Associates of Richmond, Inc.

Richmond, Virginia, 23230, United States

Location

Carilion Clinic

Roanoke, Virginia, 24014, United States

Location

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Hospital Britanico de Buenos Aires

Buenos Aires, 1280AEB, Argentina

Location

El Cruce Hospital

Buenos Aires, Argentina

Location

Fundacion Favaloro

Ciudad Autonoma Buenos Aires, C1093AAS, Argentina

Location

Hospital Italiano de Buenos Aires

Ciudad Autonoma Buenos Aires, C1093AAS, Argentina

Location

Hospital Italiano de Cordoba

Córdoba, Argentina

Location

Centro Medico 21 de Diciembre

Santa Fe, Argentina

Location

Lady Davis Carmel Medical Centre

Haifa, 34362, Israel

Location

Hadassah-Hebrew University Hospital

Jerusalem, 9112001, Israel

Location

Rabin Medical Center

Petah Tiva, 49100, Israel

Location

The Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

CardioPulmonary Research Center

Guaynabo, 00968, Puerto Rico

Location

Related Publications (1)

• Nathan SD, Argula R, Trivieri MG, Aziz S, Gay E, Medarov B, Parambil J, Raina A, Risbano MG, Thenappan T, Soto JS, Bell H, Lacasse V, Sista P, Di Marino M, Smart A, Hawkes B, Nelson E, Bull T, Tapson V, Waxman A. Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results. Eur Respir J. 2024 Jun 6;63(6):2400172. doi: 10.1183/13993003.00172-2024. Print 2024 Jun.

  PMID: 38811045 DERIVED

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Per sponsor decision, the study was terminated early. Data were not collected for the secondary outcome measures due to study termination and lack of appropriate sample size.

Results Point of Contact

• Title: United Therapeutics Global Medical Information
• Organization: United Therapeutics

304perfectstudy@lungbiotechnology.com

240-821-1881

Study Officials

• Medical Director

  United Therapeutics

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2018
• First Posted: April 12, 2018
• Study Start: May 8, 2018
• Primary Completion: October 13, 2022
• Study Completion: October 13, 2022
• Last Updated: November 24, 2023
• Results First Posted: November 24, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

AR (6); IL (4); US (65); PR (1)