Dose-response Study of the Safety and Efficacy of Beraprost Sodium Modified Release (BPS-MR) in Patients With Pulmonary Arterial Hypertension (PAH)
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Beraprost Sodium Modified Release
Intervention type(s): Drug
Intervention description(s): 60µg Tablets, twice a day for 12 weeks
Intervention MeSH terms: Beraprost
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: PAH