Dose-response Study of the Safety and Efficacy of Beraprost Sodium Modified Release (BPS-MR) in Patients With Pulmonary Arterial Hypertension (PAH)

This is a 12-week, international, multicenter, double-blind, three-group, dose-response
study to assess the safety and efficacy of BPS-MR in patients with PAH. Eligible patients
will have been previously diagnosed with PAH and will be on a stable course of an ERA and/or
PDE-5 inhibitor for at least 60 days prior to Baseline.

A total of approximately 36 patients will be randomized to 1 of 3 treatment groups (12 per
group) in a 1:1:1 ratio and will be stratified by PAH background therapy (ERA, PDE-5, and
both). The treatment groups consist of one MTD and two FD groups. Following randomization,
patients will begin taking active drug (60µg) orally twice daily. Patients will visit their
investigational site at Week 6 and Week 12 for study evaluations. Between visits, clinical
site personnel will contact patients by phone each week to assess tolerability, provide
instructions for a change in dosage, record changes in concomitant medications, and record
adverse events. Patients who complete the study will be offered the opportunity to continue
taking study medication in a separate open-label continuation protocol. Patients who
withdraw early from the study or who otherwise do not elect to enroll into the open-label
continuation protocol will be down-titrated off of BPS-MR at the discretion of the
Investigator, at a maximum decrement not to exceed one tablet (60µg) b.i.d. per day and a
minimum decrement of one tablet (60µg) b.i.d. per week.

Patients in the iMTD treatment group will dose escalate weekly by 60µg b.i.d. until they
reach the maximum dose of 600µg b.i.d. or they reach an intolerable dose which requires them
to down-titrate by 60µg b.i.d. In these instances and at the Investigator's discretion,
further attempts at dose escalation may be made.

The FD treatment groups will consist of a low dose group receiving 60µg b.i.d. and a high
dose group receiving 240µg b.i.d. Patients in the high dose group will dose escalate weekly
by 60µg b.i.d. until they reach the fixed dose of 240µg b.i.d. Once patients in these
treatment groups have reached their assigned maximum dose of active drug, weekly increases
in the number of placebo tablets administered will continue in order to maintain the blind.

Patients will be requested to maintain a daily diary of symptoms and study drug
administration for evaluation by clinical site personnel. Also, patients will be given the
option to contribute blood for pharmacokinetic assessment of BPS/BPS-314d plasma
concentrations at the Week 12 visit.