A Multinational, Multicenter, Study to Assess the Efficacy and Safety of BPS-314d-MR in Subjects With Pulmonary Arterial Hypertension Currently Receiving Treatment With an Endothelin Receptor Antagonist and/or a Phosphodiesterase-5 Inhibitor

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01458236
• Date of registration: 29/09/2011
• Prospective Registration: Yes
• Primary sponsor: Lung Biotechnology Inc.
• Public title: A Multinational, Multicenter, Study to Assess the Efficacy and Safety of BPS-314d-MR in Subjects With Pulmonary Arterial Hypertension Currently Receiving Treatment With an Endothelin Receptor Antagonist and/or a Phosphodiesterase-5 Inhibitor
• Scientific title: A Multinational, Multicenter, Double-blind, Randomized, Placebo-controlled, Phase III Study to Assess the Efficacy and Safety of BPS-314d-MR in Subjects With Pulmonary Arterial Hypertension Currently Receiving Treatment With an Endothelin Receptor Antagonist and/or a Phosphodiesterase-5 Inhibitor
• Date of first enrolment: November 2011
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: http://clinicaltrials.gov/show/NCT01458236
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 3

Key inclusion & exclusion criteria

Inclusion Criteria:

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 induced by
anorexigens/toxins, or PAH associated with repaired congenital systemic-to-pulmonary
shunts (repaired =5 years).

3. Clinically stable PAH as determined by the Investigator.

4. Able to walk unassisted (oxygen use allowed).

5. A 6-Minute Walk distance (6MWD) of 150 to 450 meters (inclusive) at Screening.

6. A 6MWD at the Baseline visit that is within 15% of the Screening 6MWD.

7. An average 6MWD (Screening and Baseline visits) of 150 to 450 meters (inclusive).

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) >3 mmHg/L/min.

9. Previous (within five years prior to the Baseline visit) chest radiograph consistent
with the diagnosis of PAH.

10. Has been on a current background regimen of an ERA and/or PDE-5 inhibitor for a
minimum of 90 days with at least 30 days on a stable dose of ERA and/or PDE-5
inhibitor prior to the Baseline visit.

11. 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.

12. Willing and able to comply with study requirements and restrictions.

Exclusion Criteria:

1. Has pulmonary venous hypertension, pulmonary veno-occlusive disease, pulmonary
capillary hemangiomatosis, or chronic thromboembolic pulmonary hypertension.

2. As the diagnosis of PAH may be challenging in subjects with multiple co-morbid
conditions, if the subject has the presence of two or more of the following co-morbid
conditions:

- Diabetes

- Age > 70 years

- Body Mass Index [BMI] > 35

- Past history of pulmonary embolism

- Chronic atrial fibrillation

- FEV1 of < 70% of predicted

- Systemic hypertension requiring treatment. AND

- the Sponsor does not concur, in writing, with the appropriateness of the subject
to enter the study.

3. Has a history of interstitial lung disease, unless subject has collagen vascular
disease and has had pulmonary function testing conducted within 6 months of the
Baseline visit demonstrating a total lung capacity =70% of predicted.

4. Has a history of obstructive lung disease, unless subject has had pulmonary function
testing conducted within 6 months of the Baseline visit demonstrating a forced
expiratory volume in 1 second (FEV1) of = 50% of predicted.

5. Is pregnant or lactating.

6. Has received prostanoid therapy at any time.

7. Modified dose, initiated or discontinued any PAH medication within 30 days prior to
the Baseline visit including, but not limited to, an ERA, PDE-5 inhibitor, oral
vasodilators, diuretics, digoxin, oxygen or calcium channel blocker (with the
exception of anticoagulants).

8. Has an ongoing hemorrhagic condition (e.g., upper digestive tract hemorrhage,
hemoptysis, etc.), or has a pre existing condition that, in the Investigator's
judgment, may increase the risk for developing hemorrhage during the study (e.g.,
hemophilia). Transient hemorrhage (e.g., epistaxis, normal menstrual bleeding,
gingival bleeding, hemorrhoidal bleeding, etc.) will not preclude enrollment

9. Has received any investigational medication, device or therapy within 30 days prior
to the Baseline visit or is scheduled to receive another investigational drug, device
or therapy during the course of the study.

10. Has any preexisting disease known to cause pulmonary hypertension other than those
listed in the Inclusion Criteria.

11. Has any musculoskeletal disease or any other disease that would significantly limit
ambulation.

12. Has any form of unrepaired or recently repaired (< 5 years) congenital
systemic-to-pulmonary shunt other than patent foramen ovale.

13. Documented history or current evidence of ischemic heart disease.

14. History of left sided myocardial disease as evidenced by a mean PCWP (or a left
ventricular end diastolic pressure) > 15 mmHg or left ventricular ejection fraction <
40% as assessed by either multigated angiogram, angiography or echocardiography, or
left ventricular shortening fraction <22% as assessed by echocardiography. Note that
subjects in whom abnormal left ventricular function is attributed entirely to
impaired left ventricular filling due to the effects of right ventricular overload
(i.e., right ventricular hypertrophy and/or dilatation) will not be excluded.

15. Has creatinine clearance <30 (using the Crockroft-Gault formula) or requires
hemodialysis.

16. Has Childs-Pugh class C liver cirrhosis.

17. Has had previous atrial septostomy.

18. Any other clinically significant illness that, in the opinion of the Investigator,
might put the subject at risk of harm during the study or might adversely affect the
interpretation of the study data.



Age minimum: 18 Years
Age maximum: 80 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: Placebo

Drug: Beraprost Sodium 314d Modified Release Tablets

Primary Outcome(s)

Time-to-clinical-worsening [Time Frame: up to 252 weeks]

Secondary Outcome(s)

Borg Dyspnea Score [Time Frame: up to 252 weeks]

pro-BNP levels (Pro-B Type Brain Natriuretic Peptide) [Time Frame: up to 252 weeks]

6 Minute Walk Distance (6MWD) [Time Frame: up to 252 weeks]

World Health Organization Functional Class (WHO) [Time Frame: up to 252 weeks]

Secondary ID(s)

BPS-314d-MR-PAH-301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors