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

NCT01458236 | Withdrawn Phase 3 DMC

• 1 other identifier: BPS-314d-MR-PAH-301
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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 (ERA) and/or a Phosphodiesterase-5 Inhibitor (PDE-5 inhibitor). Approximately 100 centers will be participating in the study. Approximately 630 eligible subjects will be randomized 1:1 into two groups, BPS-314d-MR (active) or placebo study drug.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• Time-to-clinical-worsening

  Clinical worsening events: * All-cause death * Non-planned PAH-related hospitalization (i.e. for at least 24 hours caused by a clinical condition related to PAH such as right heart failure, arrhythmia, syncope, hemoptysis, chest pain or dyspnea). * Addition of parenteral (i.e. IV or SQ) prostanoid therapy * ≥15% decrease from baseline in 6MWD, confirmed by 2 consecutive tests performed 1 to 28 days apart * Increase from Baseline Visit in WHO functional class

  up to 252 weeks

Secondary Outcomes (4)

• World Health Organization Functional Class (WHO)

  up to 252 weeks

• Borg Dyspnea Score

  up to 252 weeks

• pro-BNP levels (Pro-B Type Brain Natriuretic Peptide)

  up to 252 weeks

• 6 Minute Walk Distance (6MWD)

  up to 252 weeks

Study Arms (2)

BPS-314d-MR

EXPERIMENTAL

Available as 15 μg and 60 μg tablets for oral, twice daily (BID) administration.

Drug: Beraprost Sodium 314d Modified Release Tablets

Placebo

EXPERIMENTAL

Placebo tablets, which are identical in size and appearance to those containing BPS-314d-MR and are for oral, BID administration, will be utilized in subjects assigned to the placebo study drug treatment group.

Drug: Placebo

Interventions

Beraprost Sodium 314d Modified Release Tablets DRUG

Available as 15 μg and 60 μg tablets for oral, twice daily (BID) administration

BPS-314d-MR

Placebo DRUG

Placebo tablets, which are identical in size and appearance to those containing BPS-314d-MR and are for oral, BID administration, will be utilized in subjects assigned to the placebo study drug treatment group

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age 18 to 80 years (inclusive).
• 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).
• Clinically stable PAH as determined by the Investigator.
• Able to walk unassisted (oxygen use allowed).
• A 6-Minute Walk distance (6MWD) of 150 to 450 meters (inclusive) at Screening.
• A 6MWD at the Baseline visit that is within 15% of the Screening 6MWD.
• An average 6MWD (Screening and Baseline visits) of 150 to 450 meters (inclusive).
• 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.
• Previous (within five years prior to the Baseline visit) chest radiograph consistent with the diagnosis of PAH.
• 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.
• 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.
• Willing and able to comply with study requirements and restrictions.

You may not qualify if:

• Has pulmonary venous hypertension, pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, or chronic thromboembolic pulmonary hypertension.
• 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.
• 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.
• 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.
• Is pregnant or lactating.
• Has received prostanoid therapy at any time.
• 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).

Sponsors & Collaborators

• Lung Biotechnology PBC: lead

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

beraprost

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2011
• First Posted: October 24, 2011
• Study Start: November 1, 2011
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: May 14, 2012

Record last verified: 2012-05