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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
112
Sodium tablets
Placebo tablets, which are identical in size and appearance to those containing Esuberaprost.
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.
Time frame: Baseline up to Month 7
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.
Time frame: 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.
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The University of Alabama at Birmingham
Birmingham, Alabama, United States
Cedars-Sinai Medical Center
Beverly Hills, California, United States
University of California San Diego Medical Center
La Jolla, California, United States
University of California Los Angeles UCLA
Los Angeles, California, United States
West Los Angeles VA Healthcare Center
Los Angeles, California, United States
Santa Barbara Pulmonary Associates
Santa Barbara, California, United States
Stanford Hospital and Clinics
Stanford, California, United States
Harbor-UCLA Medical Center
Torrance, California, United States
Allianz Research Institute
Westminster, California, United States
University of Colorado Health Sciences Center
Aurora, Colorado, United States
...and 35 more locations
Time frame: 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.
Time frame: 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.
Time frame: Baseline up to Month 7