A Multi-Center, Open-Label, Multiple Dose, Dose Finding Study Exploring the Safety and Tolerability of Beraprost Sodium Modified Release in PAH Patients
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.
Pulmonary Arterial Hypertension
Drug: Beraprost sodium modified release
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multi-Center, Open-Label, Multiple Dose, Dose Finding Study Exploring the Safety and Tolerability of Beraprost Sodium Modified Release in PAH Patients|
- To determine the maximum tolerated dose (MTD) of BPS-MR in pulmonary arterial hypertension (PAH) patients, following chronic, twice-daily administration. [ Time Frame: 10 Weeks ] [ Designated as safety issue: Yes ]
- To assess the effect of BPS-MR on the following: Safety (adverse events, physical exam, vital signs, tolerability to BPS-MR, clinical laboratory parameters, electrocardiogram findings) Patient pharmacokinetic parameters at MTD, including estimates of [ Time Frame: 19 Weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2009|
|Study Completion Date:||September 2010|
|Primary Completion Date:||September 2010 (Final data collection date for primary outcome measure)|
Drug: Beraprost sodium modified release
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:
- The Treatment Phase and
- 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.
|United States, California|
|Harbor-UCLA Medical Center|
|Torrance, California, United States, 90502|
|United States, Pennsylvania|
|Allegheny General Hospital|
|Pittsburgh, Pennsylvania, United States, 15212|
|United States, Texas|
|UTSW Medical Center|
|Dallas, Texas, United States, 8550|
|Universite Libre de Bruxelles, Hospital Erasme|
|Gastuiberg University Hospital|
|Leuven, Belgium, 3000|
|Mater Misericordiae University Hospital Ltd.|
|Study Director:||Ted Staub, MS, MEng||Study Sponsor|