A Study With BPS-314d-MR-PAH-303 in Participants With Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

— BEAT OLE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03657095
• Other study ID #: BPS-314d-MR-PAH-303
• Status: Terminated
• Phase: Phase 3
• Start date: December 10, 2018
• Est. completion date: July 20, 2019

Study information

• Verified date: September 2020
• Source: Lung Biotechnology PBC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 112
• Est. completion date: July 20, 2019
• Est. primary completion date: July 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Esuberaprost
Sodium tablets
• Placebo
Placebo tablets, which are identical in size and appearance to those containing Esuberaprost.

Locations

Country	Name	City	State
Israel	Rabin Medical Center	Petah Tikva
Israel	The Chaim Sheba Medical Center	Tel Hashomer
United States	Albany Medical Center	Albany	New York
United States	Anderson Pharmaceutical Research, LLC	Anderson	South Carolina
United States	Emory University	Atlanta	Georgia
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	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Cedars-Sinai Medical Center	Beverly Hills	California
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Bay Area Cardiology Research	Brandon	Florida
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Aurora Denver Cardiology Associates	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida Clinical Research Center	Gainesville	Florida
United States	Indiana University Health North Hospital	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of California San Diego Medical Center	La Jolla	California
United States	South Denver Cardiology Associates	Littleton	Colorado
United States	University of California Los Angeles UCLA	Los Angeles	California
United States	West Los Angeles VA Healthcare Center	Los Angeles	California
United States	University of Louisville Research Foundation	Louisville	Kentucky
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	The Mount Sinai Hospital	New York	New York
United States	Sentara Cardiovascular Research Institute	Norfolk	Virginia
United States	Florida Hospital	Orlando	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Santa Barbara Pulmonary Associates	Santa Barbara	California
United States	University of Washington Medical Center	Seattle	Washington
United States	South Miami Heart Specialists	South Miami	Florida
United States	Stanford Hospital and Clinics	Stanford	California
United States	Scott & White Memorial Hospital	Temple	Texas
United States	The University of Toledo	Toledo	Ohio
United States	Harbor-UCLA Medical Center	Torrance	California
United States	Beaumont Health	Troy	Michigan
United States	Allianz Research Institute	Westminster	California
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Lung Biotechnology PBC

Countries where clinical trial is conducted

United States,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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