Pulmonary Arterial HypertensionPhase 3NCT01458236
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
A Phase 3 study testing Beraprost Sodium 314d Modified Release Tablets in people with Pulmonary Arterial Hypertension, run by Lung Biotechnology PBC.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Beraprost Sodium 314d Modified Release Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2011to Mar 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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).
- 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
- 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 any preexisting disease known to cause pulmonary hypertension other than those listed in the Inclusion Criteria.
- Has any musculoskeletal disease or any other disease that would significantly limit ambulation.
- Has any form of unrepaired or recently repaired (< 5 years) congenital systemic-to-pulmonary shunt other than patent foramen ovale.
- Documented history or current evidence of ischemic heart disease.
- 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.
- Has creatinine clearance <30 (using the Crockroft-Gault formula) or requires hemodialysis.
- Has Childs-Pugh class C liver cirrhosis.
- Has had previous atrial septostomy.
- 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.
About this study
Official 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
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.
Read the detailed description
This study is designed to evaluate the efficacy and safety of BPS-314d-MR in subjects with PAH who are treated with background therapy such as ERA and/or a PDE-5 inhibitor.
Subjects who consent to the study will be assessed at the Screening and Baseline visits to determine eligibility for the study. Subjects meeting eligibility criteria at the Baseline visit will be enrolled into the study and treated by either active or placebo study drug. The subject, the clinical site staff and the Sponsor will be blinded to the treatment assignment. Treatment assignment will be random.
Following the Baseline visit, subjects will return to the clinical site at Week 6, Week 12, Week 20 and every 12 weeks thereafter. Subjects will undergo all scheduled efficacy and safety assessments, as defined by the protocol. Between scheduled clinical site visits, the clinical site staff will be required to contact the subject by a telephone call to assess tolerability to study drug and change subject's dosage as appropriate. Telephone calls should occur at least once weekly for the first 20 study weeks when dose changes will occur most frequently and subjects are becoming familiar with the study procedures. Telephone calls will occur at least once monthly thereafter. Subjects will be provided with an electronic diary to record doses taken and help in tracking of health issues for conversations with the clinical site staff.
Subjects will continue their participation in the study until the Sponsor formally closes the study. At that time the subject will return to the clinical site for an End of Treatment visit to complete all scheduled tests. Subjects who are participating in the study at its conclusion may be offered the opportunity to enroll in a long-term extension study. Subjects who do not continue into an extension study are required to discontinue from study drug.
Subjects will be urged to remain in the study for long-term follow-up even if study drug is discontinued.
In the event that a subject withdraws consent for participation in the study or the Investigator terminates the subject from the study the subject will return to the clinical site for an End of Treatment visit to complete all scheduled tests. After study drug has been permanently discontinued, and if the subject is terminated from the study, the subject will return to the clinical site after 30-37 days for a final Safety Follow-up visit and to return any remaining study drug.
The optional Pharmacokinetic (PK) evaluation will be offered to all study subjects at clinical sites. Subjects within those sites will decide if they wish to participate in the optional PK evaluation. For those subjects electing to participate, two blood samples will be collected at three clinical site visits (Weeks 6, 12 and 20).
The optional hemodynamic sub-study will be offered to all study subjects at clinical sites. All subjects at the selected research centers will be offered the opportunity to volunteer in the sub-study. Hemodynamic measurements will be assessed by Right Heart Catheterization (RHC). For those subjects who consent to the RHC, the RHC procedure will be performed at the Baseline visit and during Week 20.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Beraprost Sodium 314d Modified Release Tablets, Placebo
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beraprost Sodium 314d Modified Release TabletsDrug
Available as 15 μg and 60 μg tablets for oral, twice daily (BID) administration
PlaceboDrug
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
| Study group | Role | What they receive |
|---|---|---|
| BPS-314d-MR | Experimental | Available as 15 μg and 60 μg tablets for oral, twice daily (BID) administration. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: up to 252 weeks
Secondary outcomes (4)
World Health Organization Functional Class (WHO)
The outcome will be measured at baseline (Day 1) and at each visit (From baseline to week 6 visit, to week 12 visit, to week 20 visit, to quaterly follow up visits, to End of treatment visit)
Measured: up to 252 weeks
Borg Dyspnea Score
The outcome will be measured at baseline (Day 1) and at each visit (From baseline to week 6 visit, to week 12 visit, to week 20 visit, to quaterly follow up visits, to End of treatment visit)
Measured: up to 252 weeks
pro-BNP levels (Pro-B Type Brain Natriuretic Peptide)
The outcome will be measured at baseline (Day 1) and at each visit (From baseline to week 6 visit, to week 12 visit, to week 20 visit, to quaterly follow up visits, to End of treatment visit)
Measured: up to 252 weeks
6 Minute Walk Distance (6MWD)
The outcome will be measured at baseline (Day 1) and at each visit (From baseline to week 6 visit, to week 12 visit, to week 20 visit, to quaterly follow up visits, to End of treatment visit)
Measured: up to 252 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2011 (estimated)
- Study startNov 2011
- Primary completionMar 2016 (estimated)
- Study completionMar 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lung Biotechnology PBC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01458236
- Sponsor's protocol ID
- BPS-314d-MR-PAH-301
- Status last verified
- May 2012
- First submitted
- 29 Sep 2011
- Last updated
- 14 May 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01458236
- Acronym / sponsor ID
- BPS-314d-MR-PAH-301
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Lung Biotechnology PBCIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Mar 2016 (estimated)
- Study completion
- Mar 2016 (estimated)
- First posted
- 24 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study is designed to evaluate the efficacy and safety of BPS-314d-MR in subjects with PAH who are treated with background therapy such as ERA and/or a PDE-5 inhibitor.
Subjects who consent to the study will be assessed at the Screening and Baseline visits to determine eligibility for the study. Subjects meeting eligibility criteria at the Baseline visit will be enrolled into the study and treated by either active or placebo study drug. The subject, the clinical site staff and the Sponsor will be blinded to the treatment assignment. Treatment assignment will be random.
Following the Baseline visit, subjects will return to the clinical site at Week 6, Week 12, Week 20 and every 12 weeks thereafter. Subjects will undergo all scheduled efficacy and safety assessments, as defined by the protocol. Between scheduled clinical site visits, the clinical site staff will be required to contact the subject by a telephone call to assess tolerability to study drug and change subject's dosage as appropriate. Telephone calls should occur at least once weekly for the first 20 study weeks when dose changes will occur most frequently and subjects are becoming familiar with the study procedures. Telephone calls will occur at least once monthly thereafter. Subjects will be provided with an electronic diary to record doses taken and help in tracking of health issues for conversations with the clinical site staff.
Subjects will continue their participation in the study until the Sponsor formally closes the study. At that time the subject will return to the clinical site for an End of Treatment visit to complete all scheduled tests. Subjects who are participating in the study at its conclusion may be offered the opportunity to enroll in a long-term extension study. Subjects who do not continue into an extension study are required to discontinue from study drug.
Subjects will be urged to remain in the study for long-term follow-up even if study drug is discontinued.
In the event that a subject withdraws consent for participation in the study or the Investigator terminates the subject from the study the subject will return to the clinical site for an End of Treatment visit to complete all scheduled tests. After study drug has been permanently discontinued, and if the subject is terminated from the study, the subject will return to the clinical site after 30-37 days for a final Safety Follow-up visit and to return any remaining study drug.
The optional Pharmacokinetic (PK) evaluation will be offered to all study subjects at clinical sites. Subjects within those sites will decide if they wish to participate in the optional PK evaluation. For those subjects electing to participate, two blood samples will be collected at three clinical site visits (Weeks 6, 12 and 20).
The optional hemodynamic sub-study will be offered to all study subjects at clinical sites. All subjects at the selected research centers will be offered the opportunity to volunteer in the sub-study. Hemodynamic measurements will be assessed by Right Heart Catheterization (RHC). For those subjects who consent to the RHC, the RHC procedure will be performed at the Baseline visit and during Week 20.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BPS-314d-MR | Experimental | Drug: Beraprost Sodium 314d Modified Release TabletsAvailable as 15 μg and 60 μg tablets for oral, twice daily (BID) administration. |
| Placebo | Experimental | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (26 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Beraprost Sodium 314d Modified Release TabletsAvailable as 15 μg and 60 μg tablets for oral, twice daily (BID) administration | Drug | BPS-314d-MR |
| PlaceboPlacebo 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 |
Primary outcome
Time-to-clinical-worsening
Time frame: up to 252 weeks
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
4 secondary outcomes
World Health Organization Functional Class (WHO)
Time frame: up to 252 weeks
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Beraprost Sodium 314d Modified Release Tablets in people with Pulmonary Arterial Hypertension, run by Lung Biotechnology PBC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 14 May 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time-to-clinical-worsening (time frame: up to 252 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2012.