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
Intervention: Beraprost sodium modified release
Intervention description: Tablets 60mcg
Intervention MeSH terms: Beraprost
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Is male or female between the ages of 18 and 75 years of age, inclusive;

          2. Has either idiopathic or familial PAH, PAH associated with collagen vascular disease,
             or PAH induced by anorexigens;

          3. Is clinically stable, as determined by the investigator;

          4. Has previously undergone a cardiac catheterization which is consistent with PAH,
             specifically PAPm ≥25 mmHg (at rest), PCWP (or left ventricular end diastolic
             pressure) ≤15 mmHg, and PVR >3 wood units;

          5. Has been on a course of an endothelin receptor antagonist (ERA) or phosphodiesterase
             inhibitor (PDE-5) or the combination for at least 90 days at the time of the Baseline
             visit;

          6. Has an unencouraged six-minute walk distance (6MWD) between 300 and 600 meters at the
             Screening visit;

          7. Is able to communicate effectively with study personnel;

          8. Is considered to be reliable, willing, cooperative and compliant with the study
             protocol requirements;

          9. Provides voluntary, written informed consent before participating in the study;

         10. Is, if female, physiologically incapable of childbearing or is practicing an
             acceptable method of birth control (i.e., surgical sterilization, approved hormonal
             contraceptives, barrier methods [such as a condom or diaphragm] used with a
             spermicide, or an intrauterine device).

        Exclusion Criteria:

          1. Has pulmonary venous hypertension, pulmonary veno-occlusive disease, pulmonary
             capillary hemangiomatosis, severe chronic obstructive pulmonary disease, pulmonary
             hypertension related to congenital heart disease, or chronic thromboembolic pulmonary
             hypertension;

          2. Is pregnant or lactating;

          3. Has a known intolerance to beraprost sodium or prostanoids;

          4. Has a pre-existing condition that could interfere with the absorption, distribution,
             metabolism, or excretion of drugs;

          5. Current use of tobacco products;

          6. Known history of syncope;

          7. Has, in the opinion of the Investigator, any concomitant disease other than those
             accepted as part of the inclusion criteria that would compromise the patient or the
             study;

          8. Has had a change in or discontinued any PAH medication (with the exception of
             anticoagulants) within 30 days prior to the Baseline visit;

          9. Has received any prostanoid therapy within the 30 days prior to the Baseline visit or
             be scheduled to receive additional prostanoid therapy during the study except for
             acute vasodilatory testing;

         10. Has received any investigational medication within 30 days prior to the Baseline visit
             or be scheduled to receive another investigational drug during the course of this
             study;

         11. In the opinion of the investigator, may be unable to comply with the study protocol;

         12. Has any preexisting disease known to cause pulmonary hypertension (e.g., obstructive
             lung disease, parasitic disease affecting the pulmonary system, sickle cell anemia,
             mitral valve stenosis, portal hypertension) other than those listed in the inclusion
             criteria;

         13. Has donated blood or plasma or has lost a volume of blood >450 mL within six weeks
             prior to the Baseline visit.

         14. Has an ongoing hemorrhagic condition (e.g. upper digestive track hemorrhage,
             hemoptysis, etc.) or has a pre-existing condition that, in the investigator's
             judgement, may increase the risk for developing hemorrhage during the study (e.g.
             hemophilia). However, transient hemorrhage (e.g. epistaxis, normal menstrual bleeding,
             gingival bleeding, hemorrhoidal hemorrhage, etc.) would not preclude enrollment