A Study With BPS-314d-MR-PAH-303 in Participants With Pulmonary Arterial Hypertension (BEAT OLE)
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|ClinicalTrials.gov Identifier: NCT03657095|
Recruitment Status : Terminated (The pivotal study, BPS-314d-MR-PAH-302 (NCT01908699), failed to demonstrate efficacy.)
First Posted : September 4, 2018
Results First Posted : September 7, 2020
Last Update Posted : September 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Arterial Hypertension||Drug: Esuberaprost Drug: Placebo||Phase 3|
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 (Clinical Trial)|
|Actual Enrollment :||112 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Masking Description:||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.|
|Official Title:||An Open-label Extension of BPS-314d-MR-PAH-302 in Pulmonary Arterial Hypertension Patients|
|Actual Study Start Date :||December 10, 2018|
|Actual Primary Completion Date :||July 20, 2019|
|Actual Study Completion Date :||July 20, 2019|
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).
Other Name: 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).
Other Name: Beraprost Sodium 314d Modified Release tablets
Placebo tablets, which are identical in size and appearance to those containing Esuberaprost.
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to Month 7 ]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.
- Area Walked for the 6 Minute Walk Distance (6MWD) Test [ Time Frame: Week 4 and then every 3 months until study termination (Month 7) ]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.
- Borg Dyspnea Score [ Time Frame: Week 4 and then every 3 months until study termination (Month 7) ]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.
- Number of Participants in Each Category of the World Health Organization (WHO) Functional Class (FC) [ Time Frame: Week 4 and then every 3 months until study termination (Month 7) ]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.
- Number of Participants With a TEAE of N-terminal Pro-brain Natriuretic Peptide (NT-pro-BNP) Increased [ Time Frame: Baseline up to Month 7 ]A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03657095