Pulmonary Arterial Hypertension
Conditions
Brief summary
This is an open-label study for patients who participated in the BPS-MR-PAH-203 study and have volunteered to continue treatment for PAH with Beraprost Sodium Modified Release (BPS-MR) tablets.
Detailed description
Eligible patients who participated in BPS-MR-PAH-203 and who elect to continue receiving study drug in an open-label extension.Each patient will return to the clinic following enrollment in the study at 3, 6, and 12 months, and annually thereafter for assessment. Patients will be called by study personnel to assess adverse events and concomitant medications at Month 9, and at 3 month intervals following the annual visit. At the End of Study visit, patients discontinuing study drug will be down-titrated off of BPS-MR at the discretion of the Investigator, at a maximum decrement of one tablet (60µg) b.i.d. per day and a minimum decrement of one tablet (60µg) b.i.d. per week. Likewise, patients who withdraw early from the study will be down-titrated off of BPS-MR in the same manner. Upon completion of down-titration, patients will return to the clinic for a final Closeout visit. Currently enrolled patients may be invited to participate in an optional four times daily (QID) dosing substudy of BPS-MR with total daily dose of BPS-MR achieved previously in the main study. Patients will return to the clinic for baseline visit, week 12, and then will follow the visit schedule provided to them in BPS-MR-PAH-204 main study.
Interventions
Sponsors
Lung Biotechnology PBC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients who remained on study drug and completed all assessments during the Treatment Phase of Study BPS MR PAH 203 are eligible for this study. * 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.
Exclusion criteria
* Patients who discontinued study drug during the previous study (BPS MR PAH 203) for any reason (e.g. treatment related adverse events) are not eligible for entry into this study. * Patients who are pregnant or lactating are excluded from participation in the open-label extension.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE) | Up to 42 months | 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-204 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 |
| Number of Reported Treatment-Emergent Adverse Events | Up to 42 months | 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-204 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Six-Minute-Walk Distance (6MWD) | Baseline and 42 months | Area used for the Six Minute Walk Test (6MWT) was pre-measured at 30 meters in length. Rest periods were allowed if patient could no longer continue. If patient needed to rest, he/she could stand or sit and then begin again when rested but the clock continued to run. At the end of 6 minutes, the tester called stop while stopping the watch and then measured the distance walked. For purposes of the 6MWT, if patient was assessed at Baseline using oxygen therapy, all future 6MWT were conducted in the same manner. All efficacy results are descriptive; no statistical analysis was conducted. |
| Change in Borg Dyspnea Score | Baseline and 42 months | The modified 0-10 category-ratio Borg scale consists of an 11-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (for the best condition) and 10 (for the worst condition) with nonlinear spacing of verbal descriptors of severity corresponding to specific numbers. The participant chose the number or the verbal descriptor to reflect presumed ratio properties of sensation or symptom intensity. Baseline was defined as the last non-missing evaluation preceding the first dose of study drug in study BPS-MR-PAH-203. Only participants with both a measurement at baseline and at the given visit are presented. All efficacy results are descriptive; no statistical analysis was conducted. |
| Number of Participants That Experienced Clinical Worsening | Up to 42 months | Number of Participants that experienced Clinical Worsening in the opinion of the Investigator. Clinical Worsening was defined as any of these events following the Baseline visit: Death, Transplantation or atrial septostomy, Clinical deterioration as defined by: Hospitalization as a result of PAH symptoms or Initiation of any new PAH specific therapy (e.g. ERA, PDE-5 inhibitor, prostanoid). All efficacy results are descriptive; no statistical analysis was conducted. |
| Number of Participants With a Change in WHO Functional Class | Baseline and 42 months | Change from Baseline in participant clinical status was recorded according to the World Health Organization (WHO) Functional Class. A change from lower to higher functional class (i.e. 'III to IV' or 'II to III') was considered as a deterioration. A change from higher to lower functional class (i.e. 'III to II' or 'II to I') was considered as an improvement. All efficacy results are descriptive; no statistical analysis was conducted. |
Countries
Belgium, Czechia, Germany, Ireland, Romania, United States
Participant flow
Pre-assignment details
A Protocol Amendment was to include an optional arm investigating Beraprost Sodium Modified Release Tablets administered four times daily (QID), however, no participants were enrolled into this arm.
Participants by arm
| Arm | Count |
|---|---|
| Beraprost Sodium Beraprost Sodium Modified Release Tablet, 60 micrograms(mcg), twice a day dosing | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 2 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Non-Compliance | 1 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Beraprost Sodium |
|---|---|
| Age, Continuous | 46.5 years STANDARD_DEVIATION 14.16 |
| Borg Dyspnea Score | 3.2 score STANDARD_DEVIATION 1.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 5 Participants |
| Six-Minute Walk Distance | 360.7 meters STANDARD_DEVIATION 78 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 31 |
| other Total, other adverse events | 26 / 31 |
| serious Total, serious adverse events | 11 / 31 |
Outcome results
Primary
Number of Reported Treatment-Emergent Adverse Events
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-204 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.
Time frame: Up to 42 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Beraprost Sodium | Number of Reported Treatment-Emergent Adverse Events | 230 TEAEs |
Primary
Number of Subjects Reporting 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-204 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
Time frame: Up to 42 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Beraprost Sodium | Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE) | 27 Participants |
Secondary
Change in Borg Dyspnea Score
The modified 0-10 category-ratio Borg scale consists of an 11-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (for the best condition) and 10 (for the worst condition) with nonlinear spacing of verbal descriptors of severity corresponding to specific numbers. The participant chose the number or the verbal descriptor to reflect presumed ratio properties of sensation or symptom intensity. Baseline was defined as the last non-missing evaluation preceding the first dose of study drug in study BPS-MR-PAH-203. Only participants with both a measurement at baseline and at the given visit are presented. All efficacy results are descriptive; no statistical analysis was conducted.
Time frame: Baseline and 42 months
Population: Only participants with both a measurement at Baseline and at the End of Study visit are presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Beraprost Sodium | Change in Borg Dyspnea Score | 0.86 scores on a scale | Standard Deviation 1.89 |
Secondary
Change in Six-Minute-Walk Distance (6MWD)
Area used for the Six Minute Walk Test (6MWT) was pre-measured at 30 meters in length. Rest periods were allowed if patient could no longer continue. If patient needed to rest, he/she could stand or sit and then begin again when rested but the clock continued to run. At the end of 6 minutes, the tester called stop while stopping the watch and then measured the distance walked. For purposes of the 6MWT, if patient was assessed at Baseline using oxygen therapy, all future 6MWT were conducted in the same manner. All efficacy results are descriptive; no statistical analysis was conducted.
Time frame: Baseline and 42 months
Population: Only participants with both a measurement at Baseline and at the End of Study visit are presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Beraprost Sodium | Change in Six-Minute-Walk Distance (6MWD) | 24.09 meters | Standard Deviation 81.01 |
Secondary
Number of Participants That Experienced Clinical Worsening
Number of Participants that experienced Clinical Worsening in the opinion of the Investigator. Clinical Worsening was defined as any of these events following the Baseline visit: Death, Transplantation or atrial septostomy, Clinical deterioration as defined by: Hospitalization as a result of PAH symptoms or Initiation of any new PAH specific therapy (e.g. ERA, PDE-5 inhibitor, prostanoid). All efficacy results are descriptive; no statistical analysis was conducted.
Time frame: Up to 42 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Beraprost Sodium | Number of Participants That Experienced Clinical Worsening | Death | 1 Participants |
| Beraprost Sodium | Number of Participants That Experienced Clinical Worsening | Hospitalization As A Result of PAH Symptoms | 2 Participants |
| Beraprost Sodium | Number of Participants That Experienced Clinical Worsening | New PAH Therapies | 4 Participants |
| Beraprost Sodium | Number of Participants That Experienced Clinical Worsening | Transplantation or atrial septostomy | 0 Participants |
Secondary
Number of Participants With a Change in WHO Functional Class
Change from Baseline in participant clinical status was recorded according to the World Health Organization (WHO) Functional Class. A change from lower to higher functional class (i.e. 'III to IV' or 'II to III') was considered as a deterioration. A change from higher to lower functional class (i.e. 'III to II' or 'II to I') was considered as an improvement. All efficacy results are descriptive; no statistical analysis was conducted.
Time frame: Baseline and 42 months
Population: Only participants with both a measurement at Baseline and at the End of Study visit are presented.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Beraprost Sodium | Number of Participants With a Change in WHO Functional Class | Improved: Change from Class II to Class I | 2 Participants |
| Beraprost Sodium | Number of Participants With a Change in WHO Functional Class | Improved: Change from Class III to Class II | 7 Participants |
| Beraprost Sodium | Number of Participants With a Change in WHO Functional Class | Deteriorated: Change from Class II to Class III | 5 Participants |
| Beraprost Sodium | Number of Participants With a Change in WHO Functional Class | Deteriorated: Change from Class III to Class IV | 1 Participants |
| Beraprost Sodium | Number of Participants With a Change in WHO Functional Class | No Change in Class | 10 Participants |