Dose-response Study of the Safety and Efficacy of Beraprost Sodium Modified Release (BPS-MR) in Patients With Pulmonary Arterial Hypertension (PAH)

NCT00989963 | Completed Phase 2 Results

• 1 other identifier: BPS-MR-PAH-203
• Study Type: interventional
• Target: 36
• Locations: 6 countries
• Sites: 17

Brief Summary

This is a 12-week, international, multicenter, double-blind, three-group, dose-response study to assess the safety and efficacy of BPS-MR in patients with PAH. Eligible patients will have been previously diagnosed with PAH and will be on a stable course of an ERA and/or PDE-5 inhibitor for at least 60 days prior to Baseline. Patients will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio and will be stratified by PAH background therapy (Endothelium Receptor Antagonist (ERA), Phosphodiesterase-5 (PDE-5), and both). The treatment groups consist of one Maximum Tolerated Dose (MTD) and two Fixed Dose (FD) groups. Following randomization, patients will begin taking active drug (60µg) orally twice daily. Patients will visit their investigational site at Week 6 and Week 12 for study evaluations.

Conditions

Pulmonary Arterial Hypertension

Keywords

PAH

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Pulmonary Vascular Resistance at Week 12

  The change in Pulmonary Vascular Resistance (PVR) was evaluated from Baseline to Week 12. PVR is expressed in Wood Units or millimeters of Mercury per Liter per minute (mmHG/L/min)

  Week 12

• Change From Baseline in Cardiac Output (CO) at Week 12

  The change in Cardiac Output was evaluated from Baseline to Week 12.

  Week 12

• Change From Baseline in Pulmonary Arterial Pressure at Week 12

  The change in mean Pulmonary Arterial Pressure (mPAP) was evaluated from Baseline to Week 12.

  12 weeks

Secondary Outcomes (6)

• Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12

  Baseline, Week 6 and 12

• Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12

  Week 6 and Week 12

• Number of Participants With at Least One Post-baseline Clinically Significant Laboratory Value

  Up to Week 12

• Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities

  Up to 12 weeks

• Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12

  Baseline, Week 6 and 12

Study Arms (3)

Maximum Tolerated Dose (MTD)

EXPERIMENTAL

Patients in the MTD treatment group will dose escalate weekly by 60µg b.i.d. until they reach the maximum dose of 600µg b.i.d. or they reach an intolerable dose which requires them to down-titrate by 60µg b.i.d. In these instances and at the Investigator's discretion, further attempts at dose escalation may be made.

Drug: Beraprost Sodium Modified Release

Low Fixed Dose

EXPERIMENTAL

The low dose group will receive 60µg twice a day(b.i.d.)

Drug: Beraprost Sodium Modified Release

High Fixed Dose

EXPERIMENTAL

Patients in the high dose group will dose escalate weekly by 60µg twice a day (b.i.d.) until they reach the fixed dose of 240µg b.i.d. Once patients in these treatment groups have reached their assigned maximum dose of active drug,

Drug: Beraprost Sodium Modified Release

Interventions

Beraprost Sodium Modified Release DRUG

60µg Tablets, twice a day for 12 weeks

High Fixed Dose; Low Fixed Dose; Maximum Tolerated Dose (MTD)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• IRB approved written informed consent has been obtained.
• Male or female, age 18 to 75 years (inclusive).
• Established diagnosis of pulmonary arterial hypertension that is either idiopathic or familial PAH, collagen vascular disease associated PAH, PAH induced by anorexigens, 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.
• Has a complete, unencouraged 6MWT distance of 150 to 450 meters (inclusive) at Screening.
• Previous (at any time) right heart cardiac catheterization 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 (at any time) chest radiograph consistent with the diagnosis of PAH.
• Has been on a stable course of an ERA or/and PDE-5 inhibitor for a minimum of 60 days prior to Baseline.
• Women of child-bearing potential (defined as less than 1 year post-menopausal or not surgically sterile) must be using an acceptable method of birth control or practicing abstinence. If sexually active, female patients must use a double barrier method of birth control, such as a condom and spermicidal. Patient 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.
• Has a history of interstitial lung disease, unless:
• Pulmonary Function Testing conducted within 6 months of the Baseline visit demonstrates a Total Lung Capacity ≥ 70 % of predicted.
• Has a history of obstructive lung disease, unless:
• Pulmonary Function Testing conducted within 6 months of the Baseline visit demonstrates a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of ≥ 50%.
• Is pregnant and/or lactating.
• Changed or discontinued any PAH medication within 60 days prior to the Baseline visit including, but not limited to, an ERA, PDE-5 inhibitor, or calcium channel blocker (with the exception of anticoagulants).
• 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 hemorrhage, etc.) will not preclude enrollment.
• Has donated blood or plasma, or has lost a volume of blood \>450mL within 6-weeks of the Baseline visit.
• 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.
• Has received any prostanoid therapy at any time.
• Has any preexisting disease known to cause pulmonary hypertension other than collagen vascular disease.
• Has any musculoskeletal disease or any other disease that would limit ambulation.
• Has any form of unrepaired or recently repaired (\< 5 years) congenital systemic-to-pulmonary shunt other than patent foramen ovale.
• History of pulmonary embolism or deep venous thrombosis.

Sponsors & Collaborators

• Lung Biotechnology PBC: lead

Study Sites (17)

Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Edward Heart Hospital

Naperville, Illinois, 60566, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Universite Libre de Bruxelles

Bruxellas, 1070, Belgium

Location

Catholic University of Leuven

Leuven, 3000, Belgium

Location

General Teaching Hospital

Prague, 2, 128 08, Czechia

Location

Klinikum der Universitat zu Koln

Cologne, 50937, Germany

Location

Medizinische Klinik und Poliklinik

Dresden, 01307, Germany

Location

Abt. Innere Medizin III, Medizinische Universitatsklinik

Heidelberg, 69120, Germany

Location

Universitatsklinik Leipzig Abteilung Pulmologie

Leipzig, 04103, Germany

Location

Mater Misericordiae University Hospital Ltd.

Dublin, 7, Ireland

Location

Institutul de Urgenta pentru Boli

Bucharest, 022322, Romania

Location

Institutul National de Pneumologie

Bucharest, 050159, Romania

Location

Institutul de Boli Cardiovasculare

Lasi, 700503, Romania

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Lung Biotechnology PBC Study Director
• Organization: Lung Biotechnology PBC

info@lungbiotechnology.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2009
• First Posted: October 6, 2009
• Study Start: February 1, 2010
• Primary Completion: September 13, 2011
• Study Completion: September 13, 2011
• Last Updated: September 30, 2020
• Results First Posted: September 30, 2020

Record last verified: 2020-09

Locations

DE (4); IE (1); BE (2); CZ (1); RO (3); US (6)