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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lung Biotechnology Inc.
ClinicalTrials.gov Identifier:
NCT00989963
First received: October 5, 2009
Last updated: April 16, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: Beraprost Sodium Modified Release
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A 12-week, Double-blind, International, Multicenter, Dose-response Study of the Safety and Efficacy of Beraprost Sodium Modified Release (BPS-MR) in Patients With Pulmonary Arterial Hypertension (PAH)

Resource links provided by NLM:


Further study details as provided by Lung Biotechnology Inc.:

Primary Outcome Measures:
  • Right Heart Catheterization [ Time Frame: 12 weeks after randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Exercise Capacity [ Time Frame: 6 & 12 weeks after randomization ] [ Designated as safety issue: No ]
  • World Health Organization(WHO)Functional Class. [ Time Frame: 6 &12 weeks after randomization ] [ Designated as safety issue: No ]
  • Clinical Laboratory Parameters [ Time Frame: 6 &12 Weeks after randomization ] [ Designated as safety issue: Yes ]
  • Electrocardiogram (ECG) Findings [ Time Frame: 6 & 12 weeks after randomization ] [ Designated as safety issue: Yes ]

Enrollment: 36
Study Start Date: November 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Maximum Tolerated Dose (MTD)
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
60µg Tablets, twice a day for 12 weeks
Experimental: Low Fixed Dose
The low dose group will receive 60µg twice a day(b.i.d.)
Drug: Beraprost Sodium Modified Release
60µg Tablets, twice a day for 12 weeks
Experimental: High Fixed Dose
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
60µg Tablets, twice a day for 12 weeks

Detailed Description:

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.

A total of approximately 36 patients will be randomized to 1 of 3 treatment groups (12 per group) in a 1:1:1 ratio and will be stratified by PAH background therapy (ERA, PDE-5, and both). The treatment groups consist of one MTD and two 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. Between visits, clinical site personnel will contact patients by phone each week to assess tolerability, provide instructions for a change in dosage, record changes in concomitant medications, and record adverse events. Patients who complete the study will be offered the opportunity to continue taking study medication in a separate open-label continuation protocol. Patients who withdraw early from the study or who otherwise do not elect to enroll into the open-label continuation protocol will be down-titrated off of BPS-MR at the discretion of the Investigator, at a maximum decrement not to exceed one tablet (60µg) b.i.d. per day and a minimum decrement of one tablet (60µg) b.i.d. per week.

Patients in the iMTD 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.

The FD treatment groups will consist of a low dose group receiving 60µg b.i.d. and a high dose group receiving 240µg b.i.d. Patients in the high dose group will dose escalate weekly by 60µg 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, weekly increases in the number of placebo tablets administered will continue in order to maintain the blind.

Patients will be requested to maintain a daily diary of symptoms and study drug administration for evaluation by clinical site personnel. Also, patients will be given the option to contribute blood for pharmacokinetic assessment of BPS/BPS-314d plasma concentrations at the Week 12 visit.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. IRB approved written informed consent has been obtained.
  2. Male or female, age 18 to 75 years (inclusive).
  3. 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).
  4. Clinically stable PAH as determined by the Investigator.
  5. Able to walk unassisted.
  6. Has a complete, unencouraged 6MWT distance of 150 to 450 meters (inclusive) at Screening.
  7. 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.
  8. Previous (at any time) chest radiograph consistent with the diagnosis of PAH.
  9. Has been on a stable course of an ERA or/and PDE-5 inhibitor for a minimum of 60 days prior to Baseline.
  10. 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.
  11. 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. 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.
  3. 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%.
  4. Is pregnant and/or lactating.
  5. 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).
  6. 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.
  7. Has donated blood or plasma, or has lost a volume of blood >450mL within 6-weeks of the Baseline visit.
  8. 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.
  9. Has received any prostanoid therapy at any time.
  10. Has any preexisting disease known to cause pulmonary hypertension other than collagen vascular disease.
  11. Has any musculoskeletal disease or any other disease that would limit ambulation.
  12. Has any form of unrepaired or recently repaired (< 5 years) congenital systemic-to-pulmonary shunt other than patent foramen ovale.
  13. History of pulmonary embolism or deep venous thrombosis.
  14. History of ischemic heart disease, including previous myocardial infarction, or symptomatic coronary artery disease, or 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 patients 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. Presence of atrial fibrillation (determined from 12-lead ECG at Screening).
  16. Any other clinically significant illness that, in the opinion of the Investigator, might put the patient at risk of harm during the study or might adversely affect the interpretation of the study data.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00989963

Locations
United States, California
Harbor-UCLA Medical Center
Torrance, California, United States, 90502
United States, Illinois
Edward Heart Hospital
Naperville, Illinois, United States, 60566
United States, New York
Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Beth Israel Medical Center
New York, New York, United States, 10003
United States, Pennsylvania
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Belgium
Universite Libre de Bruxelles
Bruxellas, Belgium, 1070
Catholic University of Leuven
Leuven, Belgium, 3000
Czech Republic
General Teaching Hospital
Praha, Czech Republic, 2, 128 08
Germany
Klinikum der Universitat zu Koln
Cologne, Germany, 50937
Medizinische Klinik und Poliklinik
Dresden, Germany, 01307
Abt. Innere Medizin III, Medizinische Universitatsklinik
Heidelberg, Germany, 69120
Universitatsklinik Leipzig Abteilung Pulmologie
Leipzig, Germany, 04103
Ireland
Mater Misericordiae University Hospital Ltd.
Dublin, Ireland, 7
Romania
Institutul National de Pneumologie
Bucuresti, Romania, 050159
Institutul de Urgenta pentru Boli
Bucuresti, Romania, 022322
Institutul de Boli Cardiovasculare
Lasi, Romania, 700503
Sponsors and Collaborators
Lung Biotechnology Inc.
  More Information

No publications provided

Responsible Party: Lung Biotechnology Inc.
ClinicalTrials.gov Identifier: NCT00989963     History of Changes
Other Study ID Numbers: BPS-MR-PAH-203
Study First Received: October 5, 2009
Last Updated: April 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Lung Biotechnology Inc.:
PAH

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Beraprost
Epoprostenol
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vasodilator Agents
Cardiovascular Agents
Antihypertensive Agents

ClinicalTrials.gov processed this record on September 30, 2014