An Open-Label Extension of BPS-MR-PAH-201 in Pulmonary Arterial Hypertension (PAH) Patients

Study Overview
=================
Brief Summary
-----------------
This is an open-label extension study for patients who participated in the BPS-MR-PAH-201 study.

Detailed Description
-----------------
This is an open-label study for patients who participated in the BPS-MR-PAH-201 study and have volunteered to continue treatment for PAH with BPS-MR tablets. Each patient will return to the clinic following enrollment in the study at 3, 6, and 12 months, and annually thereafter for assessment. Currently enrolled patients may be invited to participate in an optional four times daily (QID) dosing substudy of BPS-MR with total daily dose of BPS-MR achieved previously in the main study. Patients will return to the clinic for baseline visit, week 12, and then will follow the visit schedule provided to them in BPS-MR-PAH-202 main study.

Official Title
-----------------
An Open-Label Extension of BPS-MR-PAH-201 in Pulmonary Arterial Hypertension (PAH) Patients.

Conditions
-----------------
Pulmonary Arterial Hypertension

Intervention / Treatment
-----------------
* Drug: Beraprost Sodium Modified Release


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who remained on study drug and completed all assessments during the Treatment Phase of Study BPS-MR-PAH-201 are eligible for this study. Female patients must either be physiologically incapable of childbearing or be practicing an acceptable method of birth control (e.g. approved hormonal contraceptive, barrier method, such as condom or diaphragm, used with a spermicide, or an intrauterine device). Exclusion Criteria: Patients who discontinued study drug during the previous study (BPS-MR-PAH-201) for any reason (e.g. treatment related adverse events) are not eligible for entry into this study. Patients who are pregnant or lactating are excluded from participation in the open-label extension.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B.I.D<br>Beraprost Sodium Modified Release Tablets, 60mcg, b.i.d (twice a day dosing) | Drug: Beraprost Sodium Modified Release<br> <br> * Other names: Beraprost Sodium Modified Release Tablet, 60 mcg;|
| Experimental: Q.I.D<br>Beraprost Sodium Modified Release Tablets, 60mcg, q.i.d (four times a day dosing) | Drug: Beraprost Sodium Modified Release<br> <br> * Other names: Beraprost Sodium Modified Release Tablet, 60 mcg;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting at Least One Treatment-Emergent Adverse Event (TEAE) | A treatment-emergent adverse event (TEAEs) is defined as an event not present prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments. AEs occurring more than 3 days after the last day study drug is taken in the study will not be included in the statistical analyses or summaries (except for subjects with adverse events leading to study drug withdrawn). Only treatment-emergent adverse events occurring during the treatment period of the BPS-MR-PAH-202 study will be summarized. Any adverse event starting prior to the first dose of study drug will be excluded from the summary analyses and only presented in the data listings. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Up to 56 months | 
| Number of Treatment Emergent Adverse Events Reported During The Study | A treatment-emergent adverse event (TEAE) is defined as an event not present prior to the initiation of the treatment or any event already present that worsens in either intensity or frequency following exposure to the treatment. AEs occurring more than 3 days after the last day study drug was taken in the study was not included in the statistical analyses or summaries (except for participants with adverse events leading to study drug withdrawn). Only TEAEs that occurred during the treatment period of the BPS-MR-PAH-202 study were summarized. Any adverse event starting prior to the first dose of study drug was excluded from the summary analyses and only presented in the data listings. All efficacy results are descriptive; no statistical analysis was conducted. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | Up to 56 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at End of Study | The area used for the Six Minute Walk Test (6MWT) was pre-measured at a minimum of 30 meters in length and at least 2 to 3 meters in width. There were no turns or significant curves to the 6-minute walk area. The length was marked with gradations to ensure the accurate measurement of the distance walked. The area was well ventilated with air temperature controlled at 20 to 23°C. Intermittent rest periods were allowed if the participant could no longer continue. If the participant needed to rest briefly, he/she could stand or sit and then begin again when rested but the clock continued to run. At the end of 6 minutes, the tester called stop while simultaneously stopping the watch and then measured the distance walked. For the purposes of the 6MWT if a participant was assessed at Baseline using oxygen therapy, then all future 6MWT were conducted in the same manner. All efficacy results are descriptive; no statistical analysis was conducted. | Baseline and 56 months | 
| Change From Baseline in Borg Dyspnea Score at End of Study | The modified 0-10 category-ratio Borg scale consists of an 11-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (for the best condition) and 10 (for the worst condition) with nonlinear spacing of verbal descriptors of severity corresponding to specific numbers. The participant chose the number or the verbal descriptor to reflect presumed ratio properties of sensation or symptom intensity. Baseline was defined as the last non-missing evaluation preceding the first dose of study drug in study BPS-MR-PAH-201. Only participants with both a measurement at baseline and at the given visit are presented. All efficacy results are descriptive; no statistical analysis was conducted. | Baseline and 56 months | 
| Number of Participants That Experienced Clinical Worsening During the Study | Number of Participants that experienced Clinical Worsening in the opinion of the Investigator. Clinical Worsening was defined as any of these events following the Baseline visit: Death, Transplantation or atrial septostomy, Clinical deterioration as defined by: Hospitalization as a result of PAH symptoms or Initiation of any new PAH specific therapy (e.g. ERA, PDE-5 inhibitor, prostanoid). All efficacy results are descriptive; no statistical analysis was conducted. | Up to 56 months | 
| Number of Participants With a Change in WHO Functional Class | Change from Baseline in participant clinical status was recorded according to the World Health Organization (WHO) Functional Class. A change from lower to higher functional class (i.e. 'III to IV' or 'II to III') was considered as a deterioration. A change from higher to lower functional class (i.e. 'III to II' or 'II to I') was considered as an improvement. All efficacy results are descriptive; no statistical analysis was conducted. | Baseline and 56 months |