Pulmonary Arterial HypertensionPhase 2NCT00781885
A Multi-Center, Open-Label, Multiple Dose, Dose Finding Study Exploring the Safety and Tolerability of Beraprost Sodium Modified Release in PAH Patients
A Phase 2 study testing Beraprost sodium modified release in people with Pulmonary Arterial Hypertension, run by Lung Biotechnology PBC at 6 sites in 3 countries.
Trial summary
This study is an international, open-label, multi-center, Phase II, multiple dose, dose-finding study to investigate the safety, tolerability and pharmacokinetic characteristics of BPS-MR tablets in male and female patients with PAH. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Beraprost sodium modified release
- Type of treatment
- Pill or oral medicine
- How many people
- 19 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 31 Jan 2009to 30 Sep 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Is male or female between the ages of 18 and 75 years of age, inclusive;
- Has either idiopathic or familial PAH, PAH associated with collagen vascular disease, or PAH induced by anorexigens;
- Is clinically stable, as determined by the investigator;
- Has previously undergone a cardiac catheterization which is consistent with PAH, specifically PAPm ≥25 mmHg (at rest), PCWP (or left ventricular end diastolic pressure) ≤15 mmHg, and PVR >3 wood units;
- Has been on a course of an endothelin receptor antagonist (ERA) or phosphodiesterase inhibitor (PDE-5) or the combination for at least 90 days at the time of the Baseline visit;
- Has an unencouraged six-minute walk distance (6MWD) between 300 and 600 meters at the Screening visit;
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- Is able to communicate effectively with study personnel;
- Is considered to be reliable, willing, cooperative and compliant with the study protocol requirements;
- Provides voluntary, written informed consent before participating in the study;
- Is, if female, physiologically incapable of childbearing or is practicing an acceptable method of birth control (i.e., surgical sterilization, approved hormonal contraceptives, barrier methods [such as a condom or diaphragm] used with a spermicide, or an intrauterine device).
Who cannot join
- Has pulmonary venous hypertension, pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, severe chronic obstructive pulmonary disease, pulmonary hypertension related to congenital heart disease, or chronic thromboembolic pulmonary hypertension;
- Is pregnant or lactating;
- Has a known intolerance to beraprost sodium or prostanoids;
- Has a pre-existing condition that could interfere with the absorption, distribution, metabolism, or excretion of drugs;
- Current use of tobacco products;
- Known history of syncope;
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- Has, in the opinion of the Investigator, any concomitant disease other than those accepted as part of the inclusion criteria that would compromise the patient or the study;
- Has had a change in or discontinued any PAH medication (with the exception of anticoagulants) within 30 days prior to the Baseline visit;
- Has received any prostanoid therapy within the 30 days prior to the Baseline visit or be scheduled to receive additional prostanoid therapy during the study except for acute vasodilatory testing;
- Has received any investigational medication within 30 days prior to the Baseline visit or be scheduled to receive another investigational drug during the course of this study;
- In the opinion of the investigator, may be unable to comply with the study protocol;
- Has any preexisting disease known to cause pulmonary hypertension (e.g., obstructive lung disease, parasitic disease affecting the pulmonary system, sickle cell anemia, mitral valve stenosis, portal hypertension) other than those listed in the inclusion criteria;
- Has donated blood or plasma or has lost a volume of blood >450 mL within six weeks prior to the Baseline visit.
- Has an ongoing hemorrhagic condition (e.g. upper digestive track hemorrhage, hemoptysis, etc.) or has a pre-existing condition that, in the investigator's judgement, may increase the risk for developing hemorrhage during the study (e.g. hemophilia). However, transient hemorrhage (e.g. epistaxis, normal menstrual bleeding, gingival bleeding, hemorrhoidal hemorrhage, etc.) would not preclude enrollment
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United States3 sites
UTSW Medical Center
Dallas, Texas, 8550
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Harbor-UCLA Medical Center
Torrance, California, 90502
Belgium2 sites
Universite Libre de Bruxelles, Hospital Erasme
Brussels
Gastuiberg University Hospital
Leuven, 3000
About this study
This study is an international, open-label, multi-center, Phase II, multiple dose, dose-finding study to investigate the safety, tolerability and pharmacokinetic characteristics of BPS-MR tablets in male and female patients with PAH.
Patients who meet the inclusion/exclusion criteria will enter the Treatment Phase at a Baseline visit. Patients will begin taking one BPS-MR tablet (60µg) twice daily (b.i.d.) escalating by one tablet b.i.d. each week to a maximum dose of 600µg (ten tablets) b.i.d or until the patient reaches their MTD. Following the achievement of the MTD, patients will be down-titrated off BPS-MR in weekly one tablet b.i.d. decrements. Patients may, alternatively, elect to continue taking the study drug at their MTD in a separate open-label extension study.
Read the detailed description
This study is an international, open-label, multi-center, Phase II, multiple dose, dose-finding study to investigate the safety, tolerability and pharmacokinetic characteristics of BPS-MR tablets in male and female patients with PAH. All patients will be receiving background therapy with either a phosphodiesterase (PDE-5) inhibitor, endothelin receptor antagonist (ERA), or the combination of these two.
The study is divided into two phases:
- The Treatment Phase and
- The Down-Titration Phase
Screening will be conducted on an outpatient basis within 21 days prior to the Baseline visit. Patients meeting the inclusion/exclusion criteria at the Baseline visit will enter the Treatment Phase and begin taking one BPS-MR tablet (60µg) b.i.d. and escalating by one tablet b.i.d. each week to a maximum dose of 600µg (ten tablets) b.i.d. or until the patient reaches an intolerable dose.
Patients who reach an intolerable dose will be instructed to continue treatment at the previous dose, which will be considered as their individual MTD. For example, if a patient attains a full week of six BPS-MR tablets b.i.d. (360µg) but is unable to tolerate seven tablets (420µg) then the patient will return to using six tablets of BPS-MR b.i.d. (360µg) for up to an additional week of treatment. In this scenario, BPS-MR 360µg b.i.d. is the patient's MTD. Patients who do not reach an intolerable dose and tolerate the full ten weeks of BPS-MR dosing will be considered to have their individual MTD as BPS-MR 600µg b.i.d.
When patients reach their individual MTD (either at 10 weeks or earlier) they will return to the site 3-7 days after for an End of Treatment Phase assessment to be evaluated for safety and, optionally, a PK assessment. Subsequent to the End of Treatment Phase visit patients will be instructed to begin down-titration off of BPS-MR in weekly increments. However, patients may alternatively elect to continue taking BPS-MR at their MTD in a separate open-label extension study.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Beraprost sodium modified release
- 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 modified releaseDrug
Tablets 60mcg
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of BPS-MR in Pulmonary Arterial Hypertension (PAH) Patients, Following Chronic, Twice-daily Administration.
Measured: 10 Weeks
Secondary outcomes (11)
Number of Participants That Reported at Least One Treatment-Emergent Adverse Event (TEAE)
A treatment-emergent adverse event (TEAE) is defined as an event not present prior to the initiation of the treatment or any event already present that worsens in either intensity or frequency following exposure to the treatment. AEs occurring more than 3 days after the last day study drug was taken in the study was not included in the statistical analyses or summaries (except for subjects with adverse events leading to study drug withdrawn). Only TEAEs that occurred during the treatment period of the BPS-MR-PAH-201 study were summarized. Any adverse event starting prior to the first dose of study drug was excluded from the summary analyses and only presented in the data listings. All efficacy results are descriptive; no statistical analysis was conducted
Measured: 19 Weeks
Change in Body Mass Index (BMI) From Baseline to Week 19
Body Mass Index (BMI) was assessed at each study visit and taken after five minutes of seated rest. Body mass index is a value derived from the mass and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is universally expressed in units of kg/m², resulting from mass in kilograms and height in meters.
Measured: Baseline and 19 weeks
Change in Weight From Baseline to Week 19
Weight was assessed at each study visit and taken after five minutes of seated rest. Weight was measured in kilograms (kg).
Measured: Baseline and 19 weeks
Change in Heart Rate From Baseline to Week 19
Heart Rate was assessed at each study visit and taken after five minutes of seated rest. Heart rate is measured in beats per minute (BPM).
Measured: Baseline and 19 weeks
Change in Body Temperature From Baseline to Week 19
Body Temperature was assessed at each study visit and taken after five minutes of seated rest. Body temperature was measured in degrees Celsius (C).
Measured: Baseline and 19 weeks
Change in Systolic Blood Pressure (SBP) From Baseline to Week 19
Systolic blood pressure was assessed at each study visit and taken after five minutes of seated rest. Systolic blood pressure was measured in millimeters of mercury (mmHg).
Measured: Baseline and 19 weeks
Change in Diastolic Blood Pressure (DBP) From Baseline to Week 19
Diastolic blood pressure was assessed at each study visit and taken after five minutes of seated rest. Diastolic blood pressure was measured in millimeters of mercury (mmHg).
Measured: Baseline and 19 weeks
Change in Respiratory Rate From Baseline to Week 19
Respiratory Rate was assessed at each study visit and taken after five minutes of seated rest. Respiratory rate was measured in breaths per minute.
Measured: Baseline and 19 weeks
Change in Electrocardiogram Intervals From Baseline to Week 19
Measured: Baseline and 19 weeks
Apparent Clearance (CL/F) of BPS-MR
Apparent clearance is defined as plasma clearance divided by absolute bioavailability per kilogram of bodyweight.
Measured: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 67
Apparent Volume of Distribution (Vz/F) of BPS-MR
Measured: pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 67
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2008 (estimated)
- Study start31 Jan 2009
- Primary completion30 Sep 2010
- Study completion30 Sep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lung Biotechnology PBC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ted Staub, MS, MEng, Study director, Study Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00781885
- Sponsor's protocol ID
- BPS-MR-PAH-201
- Status last verified
- Jun 2020
- First submitted
- 27 Oct 2008
- Last updated
- 9 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Open-Label, Multiple Dose, Dose Finding Study Exploring the Safety and Tolerability of Beraprost Sodium Modified Release in PAH Patients
- ClinicalTrials.gov ID
- NCT00781885
- Acronym / sponsor ID
- BPS-MR-PAH-201
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Lung Biotechnology PBCIndustry (pharma, biotech, devices)
- Study start
- 31 Jan 2009 (actual)
- Primary completion
- 30 Sep 2010 (actual)
- Study completion
- 30 Sep 2010 (actual)
- First posted
- 29 Oct 2008 (estimated)
- Results
- Posted 9 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an international, open-label, multi-center, Phase II, multiple dose, dose-finding study to investigate the safety, tolerability and pharmacokinetic characteristics of BPS-MR tablets in male and female patients with PAH.
Patients who meet the inclusion/exclusion criteria will enter the Treatment Phase at a Baseline visit. Patients will begin taking one BPS-MR tablet (60µg) twice daily (b.i.d.) escalating by one tablet b.i.d. each week to a maximum dose of 600µg (ten tablets) b.i.d or until the patient reaches their MTD. Following the achievement of the MTD, patients will be down-titrated off BPS-MR in weekly one tablet b.i.d. decrements. Patients may, alternatively, elect to continue taking the study drug at their MTD in a separate open-label extension study.
Detailed description
This study is an international, open-label, multi-center, Phase II, multiple dose, dose-finding study to investigate the safety, tolerability and pharmacokinetic characteristics of BPS-MR tablets in male and female patients with PAH. All patients will be receiving background therapy with either a phosphodiesterase (PDE-5) inhibitor, endothelin receptor antagonist (ERA), or the combination of these two.
The study is divided into two phases:
- The Treatment Phase and
- The Down-Titration Phase
Screening will be conducted on an outpatient basis within 21 days prior to the Baseline visit. Patients meeting the inclusion/exclusion criteria at the Baseline visit will enter the Treatment Phase and begin taking one BPS-MR tablet (60µg) b.i.d. and escalating by one tablet b.i.d. each week to a maximum dose of 600µg (ten tablets) b.i.d. or until the patient reaches an intolerable dose.
Patients who reach an intolerable dose will be instructed to continue treatment at the previous dose, which will be considered as their individual MTD. For example, if a patient attains a full week of six BPS-MR tablets b.i.d. (360µg) but is unable to tolerate seven tablets (420µg) then the patient will return to using six tablets of BPS-MR b.i.d. (360µg) for up to an additional week of treatment. In this scenario, BPS-MR 360µg b.i.d. is the patient's MTD. Patients who do not reach an intolerable dose and tolerate the full ten weeks of BPS-MR dosing will be considered to have their individual MTD as BPS-MR 600µg b.i.d.
When patients reach their individual MTD (either at 10 weeks or earlier) they will return to the site 3-7 days after for an End of Treatment Phase assessment to be evaluated for safety and, optionally, a PK assessment. Subsequent to the End of Treatment Phase visit patients will be instructed to begin down-titration off of BPS-MR in weekly increments. However, patients may alternatively elect to continue taking BPS-MR at their MTD in a separate open-label extension study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Is male or female between the ages of 18 and 75 years of age, inclusive;
- Has either idiopathic or familial PAH, PAH associated with collagen vascular disease, or PAH induced by anorexigens;
- Is clinically stable, as determined by the investigator;
- Has previously undergone a cardiac catheterization which is consistent with PAH, specifically PAPm ≥25 mmHg (at rest), PCWP (or left ventricular end diastolic pressure) ≤15 mmHg, and PVR >3 wood units;
- Has been on a course of an endothelin receptor antagonist (ERA) or phosphodiesterase inhibitor (PDE-5) or the combination for at least 90 days at the time of the Baseline visit;
Key exclusion criteria (14 listed)
- Has pulmonary venous hypertension, pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, severe chronic obstructive pulmonary disease, pulmonary hypertension related to congenital heart disease, or chronic thromboembolic pulmonary hypertension;
- Is pregnant or lactating;
- Has a known intolerance to beraprost sodium or prostanoids;
- Has a pre-existing condition that could interfere with the absorption, distribution, metabolism, or excretion of drugs;
- Current use of tobacco products;
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 modified releaseTablets 60mcg | Drug | – |
Primary outcome
Maximum Tolerated Dose (MTD) of BPS-MR in Pulmonary Arterial Hypertension (PAH) Patients, Following Chronic, Twice-daily Administration.
Time frame: 10 Weeks
11 secondary outcomes
Number of Participants That Reported at Least One Treatment-Emergent Adverse Event (TEAE)
Time frame: 19 Weeks
Change in Body Mass Index (BMI) From Baseline to Week 19
Time frame: Baseline and 19 weeks
Change in Weight From Baseline to Week 19
Time frame: Baseline and 19 weeks
Change in Heart Rate From Baseline to Week 19
Time frame: Baseline and 19 weeks
Change in Body Temperature From Baseline to Week 19
Time frame: Baseline and 19 weeks
Change in Systolic Blood Pressure (SBP) From Baseline to Week 19
Time frame: Baseline and 19 weeks
Change in Diastolic Blood Pressure (DBP) From Baseline to Week 19
Time frame: Baseline and 19 weeks
Change in Respiratory Rate From Baseline to Week 19
Time frame: Baseline and 19 weeks
Change in Electrocardiogram Intervals From Baseline to Week 19
Time frame: Baseline and 19 weeks
Apparent Clearance (CL/F) of BPS-MR
Time frame: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 67
Apparent Volume of Distribution (Vz/F) of BPS-MR
Time frame: pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 67
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Ted Staub, MS, MEng study director
Study Sponsor
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Beraprost sodium modified release in people with Pulmonary Arterial Hypertension, run by Lung Biotechnology PBC at 6 sites in 3 countries.
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 10 inclusion and 14 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: finished, as of the sponsor's last update on 9 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Belgium, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose (MTD) of BPS-MR in Pulmonary Arterial Hypertension (PAH) Patients, Following Chronic, Twice-daily Administration. (time frame: 10 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 9 Jun 2020.