Conditions: Pulmonary Arterial Hypertension
Keywords: PAH
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 36
Healthy volunteers: no

Brief summary:
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.

Patients will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio and will be stratified by PAH background therapy (Endothelium Receptor Antagonist (ERA), Phosphodiesterase-5 (PDE-5), and both). The treatment groups consist of one Maximum Tolerated Dose (MTD) and two Fixed Dose (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.

Detailed description:
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.

Arms:
arm 1: Patients in the MTD 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. arm 2: The low dose group will receive 60µg twice a day(b.i.d.) arm 3: Patients in the high dose group will dose escalate weekly by 60µg twice a day (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,

Interventions: intervention 1: Beraprost Sodium Modified Release
Intervention descriptions: intervention 1: 60µg Tablets, twice a day for 12 weeks

Protocol document: