Beraprost-314d Added-on to Tyvaso® (BEAT)

NCT01908699 | Completed Phase 3 Results DMC

• 1 other identifier: BPS-314d-MR-PAH-302
• Study Type: interventional
• Target: 273
• Locations: 2 countries
• Sites: 75

Brief Summary

This is a multicenter, double-blind, randomized, placebo-controlled Phase 3 study, to assess the efficacy and safety of BPS-314d-MR when added-on to inhaled treprostinil (Tyvaso®)in patients with pulmonary arterial hypertension. Patients new to Tyvaso, will enter a run-in period on inhaled treprostinil until 90 days of experience is achieved to ensure drug tolerability before enrolling in the study. Treatment groups consist of one active and one placebo group. Subjects will be randomly allocated in a 1:1 ratio to one of the two treatment groups.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• Number of Participants That Experienced Clinical Worsening

  The number of participants that experienced a Clinical Worsening event confirmed by Endpoint Adjudication Committee at First Maximum Severity. Clinical Worsening was defined as any of these events following the Baseline visit: Death (all causes); Hospitalization due to worsening PAH; Initiation of a parenteral (infusion or sub-cutaneous) prostacyclin, directly related to worsening PAH; Disease progression; Unsatisfactory long-term clinical response. The number of participants that experienced clinical worsening is presented; time to clinical worsening data was not measured. Given the rate of clinical worsening overall and the large number of censored observations at the end of the study, the mean survival time estimates were not available for this endpoint.

  up to 144 weeks

Secondary Outcomes (5)

• Mean Change From Baseline in Borg Dyspnea Score at Week 24

  Baseline and Week 24

• Mean Change From Baseline in NT-pro-BNP Levels at Week 24

  Baseline and Week 24

• Change in WHO Functional Class From Baseline to Week 24

  Baseline and Week 24

• Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Week 24

  Baseline and Week 24

• Number of Participants With TEAEs, Serious TEAEs, Investigations SOC TEAEs, and Serious Investigations SOC TEAEs

  up to 144 weeks

Study Arms (2)

Beraprost Sodium 314d Modified Release Tablets

EXPERIMENTAL

Available as 15 μg tablets for oral, 1 or 2 tablets four times daily (QID) administration.

Drug: Beraprost Sodium 314d Modified Release Tablets

Placebo

EXPERIMENTAL

Placebo tablets, which are identical in size and appearance to those containing BPS-314d-MR.

Drug: Placebo

Interventions

Beraprost Sodium 314d Modified Release Tablets DRUG

Available as 15 μg tablets for oral, 1 or 2 tablets four times daily (QID) administration

Beraprost Sodium 314d Modified Release Tablets

Placebo DRUG

Placebo tablets, which are identical in size and appearance to those containing BPS-314d-MR

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age 18 to 80 years (inclusive).
• Established diagnosis of pulmonary arterial hypertension that is either idiopathic or familial PAH, collagen vascular disease associated PAH, PAH associated with HIV infection, PAH induced by anorexigens/toxins, or PAH associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥1 years).
• If HIV positive, has a CD4 lymphocyte count ≥200 cells/mm3 within 30 days of Baseline Visit and is receiving current standard of care antiretroviral or other effective medication.
• At the Screening Visit, WHO functional class III or IV and who have declining or unsatisfactory clinical response to current PAH therapy.
• At the Baseline Visit, WHO functional class III or IV and who have declining or unsatisfactory clinical response to inhaled treprostinil therapy.
• Able to walk unassisted (oxygen use allowed).
• A 6-Minute Walk distance (6MWD) of ≥ 100 meters at the Screening Visit.
• Previous (within five years prior to the Baseline Visit) right heart cardiac catheterization (RHC) with findings consistent with PAH, specifically mean Pulmonary Arterial Pressure (PAPm) ≥25 mmHg (at rest), Pulmonary Capillary Wedge Pressure (PCWP) (or left ventricular end diastolic pressure) ≤15 mmHg, and Pulmonary Vascular Resistance (PVR) \>3 mmHg/L/min.
• Echocardiography excluding any clinically significant left heart disease (e.g. left sided valve disease, wall motion abnormality suggesting of myocardial infarction, left ventricular hypertrophy, etc).
• Pulmonary function tests conducted within 12 months before or during the Screening period to confirm the following:
• Total lung capacity (TLC) is at least 60% (predicted value) and
• Forced expiratory volume at one second (FEV1) of at least 50% (predicted value).
• Subjects receiving additional FDA approved PAH therapies must be stable on their current dose for at least 30 days prior to the Baseline Visit, apart from modification of anticoagulant or diuretic dosages.
• Must have completed 90 days of uninterrupted inhaled treprostinil treatment and received a stable dose of inhaled treprostinil for at least 30 days prior to Baseline to be eligible for randomization into the study.
• Women of child-bearing potential (defined as less than 1 year post-menopausal and not surgically sterile) must be practicing abstinence or using two highly effective methods of contraception (defined as a method of birth control that result in a low failure rate, i.e., less than 1% per year, such as approved hormonal contraceptives, barrier methods \[such as a condom or diaphragm\] used with a spermicide, or an intrauterine device). Subject must have a negative pregnancy test at the Screening and Baseline Visits.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from the study:
• Pregnant or lactating.
• Has previous experience with beraprost or BPS-314d (i.e., BPS-IR, BPS-MR or BPS-314d- MR).
• History of interstitial lung disease, unless subject has collagen vascular disease and has had pulmonary function testing conducted within 12 months of the Baseline Visit demonstrating a total lung capacity ≥60% of predicted.
• Has active hemorrhagic condition (e.g., upper digestive tract hemorrhage, hemoptysis, etc), or has a pre-existing condition that, in the Investigator's judgment, may increase the risk for developing hemorrhage during the study (e.g., hemophilia). Transient hemorrhage (e.g., epistaxis, normal menstrual bleeding, gingival bleeding, hemorrhoidal bleeding, etc) will not preclude enrollment.
• Has received any investigational drug, device or therapy within 30 days prior to the Baseline Visit or is scheduled to receive another investigational drug, device or therapy during the course of the study.
• Has any musculoskeletal disease or any other disease that would significantly limit ambulation.
• Has any form of unrepaired or recently repaired (\< 1 year) congenital systemic-to-pulmonary shunt other than patent foramen ovale.
• Evidence of significant coronary arterial disease with symptoms, such as angina.
• Left sided myocardial disease as evidenced by left ventricular ejection fraction \< 40%, or shortening fraction \<22%.
• Has creatinine clearance \<30 (using the Cockroft-Gault formula) or requires hemodialysis.
• Has Childs-Pugh class C liver cirrhosis.
• Has had previous atrial septostomy.
• Any other clinically significant illness or abnormal laboratory values (measured during the Screening period) that, in the opinion of the Investigator, might put the subject at risk of harm during the study or might adversely affect the interpretation of the study data.
• Anticipated survival less than 1 year due to concomitant disease.

Sponsors & Collaborators

• Lung Biotechnology PBC: lead

Study Sites (75)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Cedars-Sinai Medical Center Heart Institute

Beverly Hills, California, 90211, United States

Location

Allianz Research Institute Inc.

Fountain Valley, California, 92708, United States

Location

University of California San Francisco - Fresno

Fresno, California, 93720, United States

Location

University of California - San Diego

La Jolla, California, 92093, United States

Location

University of California Los Angeles

Los Angeles, California, 90024, United States

Location

Keck Medical Center of USC

Los Angeles, California, 90033, United States

Location

Veterans Affairs Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

Center for Advanced Pulmonary Medicine

Rancho Mirage, California, 92270, United States

Location

University of California - San Francisco

San Francisco, California, 94143, United States

Location

Cottage Pulmonary Hypertension Center

Santa Barbara, California, 93105, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Aurora Denver Cardiology Associates

Denver, Colorado, 80218, United States

Location

South Denver Cardiology Associates P.C.

Littleton, Colorado, 80120, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

Bay Area Cardiology Associates, P.A.

Brandon, Florida, 33511, United States

Location

Florida Lung, Asthma, and Sleep Institute

Celebration, Florida, 34747, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Florida College of Medicine

Jacksonville, Florida, 32209, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Florida Hospital

Orlando, Florida, 32804, United States

Location

Orlando Health Heart Institute

Orlando, Florida, 32806, United States

Location

South Miami Heart Specialists

South Miami, Florida, 33143, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Pulmonary & Critical Care of Atlanta

Atlanta, Georgia, 30342, United States

Location

Georgia Clinical Research

Austell, Georgia, 30106, United States

Location

Gwinnett Biomedical Research

Lawrenceville, Georgia, 30046, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Advocate Health and Hospitals Corporation

Oakbrook Terrace, Illinois, 60181, United States

Location

Indiana University - Health Physicians

Carmel, Indiana, 46032, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Kentuckiana Pulmonary Associates

Louisville, Kentucky, 40202, United States

Location

University of Louisville Department of Medicine

Louisville, Kentucky, 40202, United States

Location

John Ochsner Heart & Vascular Institute

New Orleans, Louisiana, 70121, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beaumont Health Systems

Troy, Michigan, 48085, United States

Location

Rutgers University Hospital

Newark, New Jersey, 07103, United States

Location

Albany Medical College

Albany, New York, 12206, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Pulmonary Health Physicians, PC

Syracuse, New York, 13210, United States

Location

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45627, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Ohio State University

Columbus, Ohio, 43221, United States

Location

University of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Anderson Pharmaceutical Research

Anderson, South Carolina, 29621, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Methodist Healthcare Clinical Trials Office

San Antonio, Texas, 78229, United States

Location

Scott & White Memorial Hospital

Temple, Texas, 76508, United States

Location

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Soroka Medical Center

Beersheba, 84101, Israel

Location

The Lady Davis Carmel Medical Center

Haifa, 3436212, Israel

Location

Hadassah University Hospital - Ein Kerem

Jerusalem, 9112001, Israel

Location

Rabin Medical Center-Beilinson Campus

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Kaplan Medical Center

Rehovot, 7610001, Israel

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

beraprost

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Lung Biotechnology PBC Study Director
• Organization: Lung Biotechnology PBC

info@lungbiotechnology.com

301-608-9292

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: July 16, 2013
• First Posted: July 26, 2013
• Study Start: May 31, 2013
• Primary Completion: February 19, 2019
• Study Completion: February 19, 2019
• Last Updated: August 3, 2020
• Results First Posted: February 28, 2020

Record last verified: 2020-07

Locations

US (69); IL (6)