A Multi-Center, Open-Label, Multiple Dose, Dose Finding Study Exploring the Safety and Tolerability of Beraprost Sodium Modified Release in PAH Patients
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension
Study type: Interventional
Phase: Phase 2

Summary: 
      This study is an international, open-label, multi-center, Phase II, multiple dose,
      dose-finding study to investigate the safety, tolerability and pharmacokinetic
      characteristics of BPS-MR tablets in male and female patients with PAH.

      Patients who meet the inclusion/exclusion criteria will enter the Treatment Phase at a
      Baseline visit. Patients will begin taking one BPS-MR tablet (60µg) twice daily (b.i.d.)
      escalating by one tablet b.i.d. each week to a maximum dose of 600µg (ten tablets) b.i.d or
      until the patient reaches their MTD. Following the achievement of the MTD, patients will be
      down-titrated off BPS-MR in weekly one tablet b.i.d. decrements. Patients may, alternatively,
      elect to continue taking the study drug at their MTD in a separate open-label extension
      study.
    

Detailed description: 
      This study is an international, open-label, multi-center, Phase II, multiple dose,
      dose-finding study to investigate the safety, tolerability and pharmacokinetic
      characteristics of BPS-MR tablets in male and female patients with PAH. All patients will be
      receiving background therapy with either a phosphodiesterase (PDE-5) inhibitor, endothelin
      receptor antagonist (ERA), or the combination of these two.

      The study is divided into two phases:

        1. The Treatment Phase and

        2. The Down-Titration Phase

      Screening will be conducted on an outpatient basis within 21 days prior to the Baseline
      visit. Patients meeting the inclusion/exclusion criteria at the Baseline visit will enter the
      Treatment Phase and begin taking one BPS-MR tablet (60µg) b.i.d. and escalating by one tablet
      b.i.d. each week to a maximum dose of 600µg (ten tablets) b.i.d. or until the patient reaches
      an intolerable dose.

      Patients who reach an intolerable dose will be instructed to continue treatment at the
      previous dose, which will be considered as their individual MTD. For example, if a patient
      attains a full week of six BPS-MR tablets b.i.d. (360µg) but is unable to tolerate seven
      tablets (420µg) then the patient will return to using six tablets of BPS-MR b.i.d. (360µg)
      for up to an additional week of treatment. In this scenario, BPS-MR 360µg b.i.d. is the
      patient's MTD. Patients who do not reach an intolerable dose and tolerate the full ten weeks
      of BPS-MR dosing will be considered to have their individual MTD as BPS-MR 600µg b.i.d.

      When patients reach their individual MTD (either at 10 weeks or earlier) they will return to
      the site 3-7 days after for an End of Treatment Phase assessment to be evaluated for safety
      and, optionally, a PK assessment. Subsequent to the End of Treatment Phase visit patients
      will be instructed to begin down-titration off of BPS-MR in weekly increments. However,
      patients may alternatively elect to continue taking BPS-MR at their MTD in a separate
      open-label extension study.
    

Intervention name(s): Beraprost sodium modified release
Intervention type(s): Drug
Intervention description(s): Tablets 60mcg
Intervention MeSH terms: Beraprost
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment