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[RegisteredTM]) 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 ([LessThanorequalTo] 90 days,[Greater Than] 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 >=1 years).
3. If HIV positive, has a 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. At the Screening Visit, WHO functional class III or IV and who have declining or
unsatisfactory clinical response to current PAH therapy.
5. At the Baseline Visit, WHO functional class III or IV and who have declining or
unsatisfactory clinical response to inhaled treprostinil therapy.
6. Able to walk unassisted (oxygen use allowed).
7. A 6-Minute Walk distance (6MWD) of >= 100 meters at the Screening Visit.
8. 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)
9. Echocardiography excluding any clinically significant left heart disease (e.g. left sided
valve disease, wall motion abnormality suggesting of myocardial infarction, left ventricular
10. Pulmonary function tests conducted within 12 months before or during the Screening
period to confirm the following:
a. Total lung capacity (TLC) is at least 60% (predicted value) and
b. Forced expiratory volume at one second (FEV1) of at least 50% (predicted value).
11. Subjects receiving additional FDA approved PAH therapies must be stable on their current
dose for at least 30 days prior to the Baseline Visit, apart from modification of
anticoagulant or diuretic dosages.
12. Must have completed 90 days of uninterrupted inhaled treprostinil treatment and received
a stable dose of inhaled treprostinil for at least 30 days prior to Baseline to be eligible for
randomization into the study.
13. 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 ofcontraception (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.
14. Willing and able to comply with study requirements and restrictions.