Clinical trial NCT03657095: A Study With BPS-314d-MR-PAH-303 in Participants With Pulmonary Arterial Hypertension
Official title: An Open-label Extension of BPS-314d-MR-PAH-302 in Pulmonary Arterial Hypertension Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: Hypertension
Familial Primary Pulmonary Hypertension
Hypertension, Pulmonary
Lung Diseases
Vascular Diseases
Cardiovascular Diseases
Respiratory Tract Diseases
Prostacyclin
Beraprost
Epoprostenol
Platelet Aggregation Inhibitors
Vasodilator Agents
Antihypertensive Agents
Lead sponsor: Lung Biotechnology PBC
Sponsor class: INDUSTRY
First posted: 2018-09-04
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Month 7
Secondary outcomes:
measure: Area Walked for the 6 Minute Walk Distance (6MWD) Test
timeFrame: Week 4 and then every 3 months until study termination (Month 7)
measure: Borg Dyspnea Score
timeFrame: Week 4 and then every 3 months until study termination (Month 7)
measure: Number of Participants in Each Category of the World Health Organization (WHO) Functional Class (FC)
timeFrame: Week 4 and then every 3 months until study termination (Month 7)
measure: Number of Participants With a TEAE of N-terminal Pro-brain Natriuretic Peptide (NT-pro-BNP) Increased
timeFrame: Baseline up to Month 7
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Beverly Hills
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles UCLA
state: California
city: Los Angeles
country: United States
facility: West Los Angeles VA Healthcare Center
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Pulmonary Associates
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Westminster
country: United States
facility: Allianz Research Institute
state: California
city: Aurora
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Denver
country: United States
facility: Aurora Denver Cardiology Associates
state: Colorado
city: Littleton
country: United States
facility: South Denver Cardiology Associates
state: Colorado
city: Brandon
country: United States
facility: Bay Area Cardiology Research
state: Florida
city: Gainesville
country: United States
facility: University of Florida Clinical Research Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: South Miami
country: United States
facility: South Miami Heart Specialists
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Pulmonary & Critical Care of Atlanta
state: Georgia
city: Austell
country: United States
facility: Georgia Clinical Research
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Health North Hospital
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: University of Louisville Research Foundation
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Troy
country: United States
facility: Beaumont Health
state: Michigan
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Toledo
country: United States
facility: The University of Toledo
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Anderson
country: United States
facility: Anderson Pharmaceutical Research, LLC
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Temple
country: United States
facility: Scott & White Memorial Hospital
state: Texas
city: Norfolk
country: United States
facility: Sentara Cardiovascular Research Institute
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
Study officials:
References: