A Study With BPS-314d-MR-PAH-303 in Participants With Pulmonary Arterial Hypertension (BEAT OLE)

An Open-label Extension of BPS-314d-MR-PAH-302 in Pulmonary Arterial Hypertension Patients

This is a multi-center, open-label study for eligible participants who were actively participating in the BPS-314d-MR-PAH-302 double-blind study (NCT01908699) at the time the study was concluded. This open-label extension (OLE) study will evaluate the safety, tolerability, and efficacy of long-term treatment with esuberaprost sodium tablets (Beraprost Sodium 314d Modified Release tablets).

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Esuberaprost; Drug: Placebo

Detailed Description

Participants will sign an informed consent to continue treatment for pulmonary arterial hypertension (PAH) with esuberaprost sodium tablets in this OLE study. At the Enrollment Visit for this OLE study, participants will begin a blinded transition from the BPS-314d-MR-PAH-302 double-blind study to this study over 4 weeks. The first dose for all participants in this OLE study will be 2 tablets. During this blinded transition, those participants on active study drug in the BPS-314d-MR-PAH-302 study will continue with blinded active study drug 4-times daily (QID); those participants who were on placebo study drug will receive 1 active tablet and 1 placebo tablet QID (blinded) during the first 2 weeks and increase to 2 active tablets QID (blinded) thereafter. After the first dose, the Investigator may adjust the dose as medically warranted. The maximum dose for this study is 30 microgram (μg) QID with a minimum accepted dose as 15 μg QID. For the first 4 weeks, contact with the participant should occur weekly to ensure up-titration to the fixed dose is tolerated and assess adverse events (AEs).

Participants will return to the clinic at Week 4 to be supplied open-label esuberaprost sodium tablets and complete protocol specified procedures. At the Week 4 Visit, participants will be dosed with two 15 μg tablets (30 μg total), administered orally QID (provided the target dose is tolerated), or follow the Investigator's (or designee's) directions if adjustment is needed. Following the Week 4 Visit, each participant will return to the clinic at Months 3, 6, 9, and 12, and quarterly thereafter for assessments.

This study is expected to continue until the first of any of the following are reached: the study drug is commercially available, the Sponsor discontinues the study, or the Sponsor offers enrollment in another study (estimated to be up to 2 years). At the conclusion of the study or if a participant discontinues the study prematurely, participants will return to the clinic for an End-of-Study (EOS) Visit. Participants will be provided instructions about down titration off esuberaprost sodium tablets by the Investigator.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
  • Tel Hashomer, Israel, 52621
    • The Chaim Sheba Medical Center
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • The University of Alabama at Birmingham
  • California
    • Beverly Hills, California, United States, 90211
      • Cedars-Sinai Medical Center
    • La Jolla, California, United States, 92093
      • University of California San Diego Medical Center
    • Los Angeles, California, United States, 90073
      • West Los Angeles VA Healthcare Center
    • Los Angeles, California, United States, 90024
      • University of California Los Angeles UCLA
    • Santa Barbara, California, United States, 93102
      • Santa Barbara Pulmonary Associates
    • Stanford, California, United States, 94305
      • Stanford Hospital and Clinics
    • Torrance, California, United States, 90502
      • Harbor-UCLA Medical Center
    • Westminster, California, United States, 92683
      • Allianz Research Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Health Sciences Center
    • Denver, Colorado, United States, 80128
      • Aurora Denver Cardiology Associates
    • Littleton, Colorado, United States, 80120
      • South Denver Cardiology Associates
  • Florida
    • Brandon, Florida, United States, 33511
      • Bay Area Cardiology Research
    • Gainesville, Florida, United States, 32610
      • University of Florida Clinical Research Center
    • Orlando, Florida, United States, 32803
      • Florida Hospital
    • South Miami, Florida, United States, 33143
      • South Miami Heart Specialists
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30342
      • Pulmonary & Critical Care of Atlanta
    • Austell, Georgia, United States, 30106
      • Georgia Clinical Research
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health North Hospital
  • Iowa
    • Iowa City, Iowa, United States, 54224
      • University of Iowa Hospitals and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University Of Louisville Research Foundation
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Troy, Michigan, United States, 48085
      • Beaumont Health
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43221
      • The Ohio State University Wexner Medical Center
    • Toledo, Ohio, United States, 43614
      • The University of Toledo
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Anderson Pharmaceutical Research, LLC
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Temple, Texas, United States, 76508
      • Scott & White Memorial Hospital
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Cardiovascular Research Institute
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participant must have been actively participating in the double-blind study, BPS-314d-MR-PAH-302 (NCT01908699), when the Sponsor concluded that study.
2. In the Investigator's opinion, participant must be competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent form (ICF) and must sign the form prior to the initiation of any study procedures.
3. Women of child-bearing potential (defined as less than 1 year post-menopausal and not surgically sterile) must be practicing abstinence or using 2 highly-effective methods of contraception (defined as a method of birth control that results in a low failure rate [that is, 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]). Participant must have a negative pregnancy test at the BPS-314d-MR-PAH-302 EOS Visit / BPS-314d-MR-PAH-303 Enrollment Visit.
4. Participant must be willing and able to comply with study requirements and restrictions.

Exclusion Criteria:

1. Participant is pregnant or lactating.
2. Participant is scheduled to receive another investigational drug, device, or therapy during the course of the study.
3. Participant is taking or intends to take any prostacyclin / prostacyclin (IP) analog or IP receptor agonist (except for treprostinil, inhaled [Tyvaso®]).
4. Participant has any other clinically significant illness or other reason that, in the opinion of the Investigator, might put the participant at risk of harm during the study or might adversely affect the interpretation of the study data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esuberaprost; Participants who received esuberaprost during the BPS-314d-MR-PAH-302 double-blind study will receive 2 tablets of 15 μg esuberaprost sodium tablets for oral administration QID for up to 7 months (which will include the 4 weeks of blinded transition).	Drug: Esuberaprost; Sodium tablets; Other Names: Beraprost Sodium 314d Modified Release tablets
Placebo Comparator: Placebo/Esuberaprost; Participants who received placebo during the BPS-314d-MR-PAH-302 double-blind study will receive 1 esuberaprost tablet and 1 placebo tablet QID during the first 2 weeks of the blinded transition and then receive 2 esuberaprost tablets QID for the rest of the study, for up to 7 months (which will include the other 2 weeks of the total 4-week blinded transition).	Drug: Esuberaprost; Sodium tablets; Other Names: Beraprost Sodium 314d Modified Release tablets; Drug: Placebo; Placebo tablets, which are identical in size and appearance to those containing Esuberaprost.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	A TEAE is any untoward medical occurrence or undesirable event(s) experienced in a participant that begins or worsens following administration of study drug, whether or not considered related to study drug by Investigator. A serious adverse event (SAE) is an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason, death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), or persistent or significant disability/incapacity. AEs included both SAEs and non-serious AEs. AEs were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 20.1. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.	Baseline up to Month 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Walked for the 6 Minute Walk Distance (6MWD) Test	Area used for the Six Minute Walk Test (6MWT) were to be pre-measured at 30 meters in length. Rest periods were to be allowed if participant could no longer continue. If participant needed to rest, he/she could have stood or sit and then begin again when rested but the clock would continue to run. At the end of 6 minutes, the tester was to call "stop" while stopping the watch and then measure the distance walked. Distance <500 meters would have suggested considerable exercise limitation; distance 500-800 meters would have suggested moderate limitation; and distance >800 meters (with no rests) would have suggested mild or no limitation. This extension study was terminated early due to the pivotal double-blind study failed to demonstrate efficacy. Therefore, efficacy data was not collected or analyzed.	Week 4 and then every 3 months until study termination (Month 7)
Borg Dyspnea Score	The modified 0-10 category-ratio Borg scale is one in which the participants were to rate the maximum level of dyspnea they experienced during the 6MWT. Scores would have ranged from 0 (for the best condition) and 10 (for the worst condition). This extension study was terminated early due to the pivotal double-blind study failed to demonstrate efficacy. Therefore, efficacy data was not collected or analyzed. Note, a summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.	Week 4 and then every 3 months until study termination (Month 7)
Number of Participants in Each Category of the World Health Organization (WHO) Functional Class (FC)	The WHO Functional Class of pulmonary hypertension is a physical activity rating scale as follows: Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms. This extension study was terminated early due to the pivotal double-blind study failed to demonstrate efficacy. Therefore, efficacy data was not collected or analyzed.	Week 4 and then every 3 months until study termination (Month 7)
Number of Participants With a TEAE of N-terminal Pro-brain Natriuretic Peptide (NT-pro-BNP) Increased	A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.	Baseline up to Month 7

Collaborators and Investigators

• Sponsor: Lung Biotechnology PBC

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2018
• Primary Completion (Actual): July 20, 2019
• Study Completion (Actual): July 20, 2019

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: August 29, 2018
• First Posted (Actual): September 4, 2018

Study Record Updates

• Last Update Posted (Actual): September 7, 2020
• Last Update Submitted That Met QC Criteria: September 3, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Vascular Diseases; Cardiovascular Diseases; Hypertension; Prostacyclin; Lung Diseases; Platelet Aggregation Inhibitors; Antihypertensive Agents; Vasodilator Agents; Hypertension, Pulmonary; Epoprostenol; Familial Primary Pulmonary Hypertension; Beraprost
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Vasodilator Agents; Platelet Aggregation Inhibitors; Beraprost
• Other Study ID Numbers: BPS-314d-MR-PAH-303

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No