The pivotal study, BPS-314d-MR-PAH-302 (NCT01908699), failed to demonstrate efficacy.

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).

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.

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.

Treatment during the first 4 weeks of this study will be double-blind. The Investigator and study staff, the participants, the monitors, and the Sponsor will remain blinded to the treatment group allocation from BPS-314d-MR-PAH-302 double-blind study (NCT01908699) and to study drug during the first 4 weeks of the OLE study while the participants transition to the OLE treatment. After the 4 weeks, the study will continue as unblinded and open label.