A multicenter, double-blind, randomized, placebo-controlled, Phase 3 study to assess the efficacy and safety of oral BPS-314d-MR added-on to treprostinil, inhaled (Tyvaso(RegisteredTM)) in subjects with pulmonary arterial hypertension
Treprostinil, inhaled (Tyvaso(TM)) is a registered treatment for PAH with an acceptable safety
profile. Oral BPS-314d-MR is under development as a prostacyclin for the treatment of PAH. This study is designed to leverage the complimentary mechanistic and pharmacokinetic differences between locally acting inhaled treprostinil and the systemic delivery of BPS-314d-MR, creating an effect that more closely approximates parenteral therapy than using either therapy alone. This study will test the hypothesis that combining these therapies will achieve a more effective and longer lasting therapeutic effect, delaying time to clinical worsening.
To preserve study blinding, the placebo tablets are identical in size, shape, color, and appearance to the BPS-314d-MR tablets. The tablet packaging and configuration for placebo tablets are also identical to active tablet.
Patients who continue to meet eligibility criteria at the Baseline Visit will be randomized into the study using a centralized randomization system, stratified by time on inhaled treprostinil, to either active or placebo study drug.
Treatment groups consist of one active and one placebo group. Subjects will be randomly
allocated in a 1:1 ratio to one of the two treatment groups. All subjects will be randomized using
a centrally administered randomization stratified by time on inhaled treprostinil (? 90 days, and amp;gt; 90 days). Randomization codes will be blocked. Block sizes will not be disclosed to
Investigators to prevent inferences about possible treatment assignments for current or future
subjects. Interactive Randomization Technology (IRT) will be utilized for the central
randomization procedure. Once all entry criteria have been met at the Baseline visit, the
Investigator or designee will access the IRT (by phone or by web) to assign the subject a
randomization number and the study drug corresponding to the assigned treatment group.
1. Male or female, age 18 to 80 years (inclusive).
2. Established diagnosis of pulmonary arterial hypertension that is either idiopathic or familial
PAH, collagen vascular disease associated PAH, PAH associated with HIV infection, PAH
induced by anorexigens/toxins, or PAH associated with repaired congenital systemic-topulmonary
shunts (repaired >=5 years).
3. If HIV positive, has CD4 lymphocyte count >=200 cells/mm3 within 30 days of Baseline Visit
and is receiving current standard of care anti-retroviral or other effective medication.
4. Showing signs of deterioration on inhaled treprostinil or having a less than optimal response
to inhaled treprostinil treatment.
5. Able to walk unassisted (oxygen use allowed).
6. A 6-Minute Walk distance (6MWD) of >= 100 meters at the Screening Visit.
7. Previous (within five years prior to the Baseline visit) right heart cardiac catheterization
(RHC) with findings consistent with PAH, specifically mean Pulmonary Arterial Pressure
(PAPm) >=25 mmHg (at rest), Pulmonary Capillary Wedge Pressure (PCWP) (or left
ventricular end diastolic pressure) <=15 mmHg, and Pulmonary Vascular Resistance (PVR)
8. Within five years prior to the Baseline visit, chest radiograph consistent with PAH.
9. Echocardiography with results consistent with PAH and the absence of any clinically
significant left heart disease (e.g. mitral valve stenosis, myocardial infarction, etc.).
10. Pulmonary function tests conducted within 6 months before or during the Screening period to
confirm the following:
a. Total lung capacity (TLC) is at least 60% (predicted value) assessed by whole body
b. Forced expiratory volume at one second (FEV1) of at least 50% (predicted value)
11. WHO functional class III to IV
12. Subjects receiving PAH therapies (i.e. ERAs, PDE-5 inhibitors) must be stable on their
current dose for at least 30 days prior to Baseline. Discontinuation or dose changes of
anticoagulants and/or dose change of diuretics are allowed.
13. Must have received a stable dose of inhaled treprostinil for at least 30 days prior to Baseline.
Those initiating therapy at the time of screening must complete 90 days of inhaled
treprostinil treatment and any concurrent background therapies before the Baseline visit to be
eligible for randomization into the study.
14. Women of child-bearing potential (defined as less than 1 year post-menopausal and not
surgically sterile) must be practicing abstinence or using two highly effective methods of
contraception (defined as a method of birth control that result in a low failure rate, i.e., less
than 1% per year, such as approved hormonal contraceptives, barrier methods [such as a
condom or diaphragm] used with a spermicide, or an intrauterine device). Subject must have
a negative pregnancy test at the Screening and Baseline visits.
15. Willing and able to comply with study requirements and restrictions.