Clinical Trial Results:
An open-label extension of BPS-MR-PAH-203 in pulmonary arterial hypertension (PAH) patients
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Summary
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EudraCT number |
2009-014453-32 |
Trial protocol |
BE IE DE CZ |
Global end of trial date |
26 Nov 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Jan 2020
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First version publication date |
31 Jan 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BPS-MR-PAH-204
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00990314 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Lung Biotechnology PBC
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Sponsor organisation address |
1040 Spring Street, Silver Spring, United States, 20910
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Public contact |
Lung Biotechnology PBC Study Director, Lung Biotechnology PBC, +1 3016089292,
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Scientific contact |
Lung Biotechnology PBC Study Director, Lung Biotechnology PBC, +1 3016089292,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
27 May 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Nov 2013
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
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.
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Protection of trial subjects |
The study was conducted in accordance with U.S. 21 CFR Parts 50, 56, and 312 and in
accordance with the Declaration of Helsinki.
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Background therapy |
Patients on background therapy (ERA alone, PDE-5 inhibitor alone, and ERA and PDE-5 inhibitor) were combined for the analysis. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 May 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 4
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Country: Number of subjects enrolled |
Czech Republic: 3
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Country: Number of subjects enrolled |
Romania: 9
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Country: Number of subjects enrolled |
United States: 15
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Worldwide total number of subjects |
31
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EEA total number of subjects |
16
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
27
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
This was an open-label study for subjects who participated in the BPS-MR-PAH-203 study and volunteered to continue treatment for PAH with BPS-MR tablets. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
A Protocol Amendment was to include an optional arm investigating Beraprost Sodium Modified Release Tablets administered four times daily (QID), however, no subjects were enrolled into this arm. | ||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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Beraprost Sodium | ||||||||||||||||||||
Arm description |
Beraprost Sodium Modified Release Tablet, 60 micrograms(mcg), twice a day dosing | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Beraprost Sodium Modified Release Tablet
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Modified-release tablet
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Routes of administration |
Oral use
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Dosage and administration details |
60 mcg twice a day
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Baseline characteristics reporting groups
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Reporting group title |
Beraprost Sodium
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Reporting group description |
Beraprost Sodium Modified Release Tablet, 60 micrograms(mcg), twice a day dosing | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Beraprost Sodium
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Reporting group description |
Beraprost Sodium Modified Release Tablet, 60 micrograms(mcg), twice a day dosing | ||
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End point title |
Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE) [1] | ||||||
End point description |
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
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End point type |
Primary
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End point timeframe |
Up to 42 months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of reported Treatment-Emergent Adverse Events [2] | ||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
Up to 42 months
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
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| No statistical analyses for this end point | |||||||
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End point title |
Change in Six-Minute-Walk Distance (6MWD) | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline and 42 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in Borg Dyspnea Score | ||||||||
End point description |
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 subjects with both a measurement at baseline and at the given visit are presented. All efficacy results are descriptive; no statistical analysis was conducted.
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End point type |
Secondary
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End point timeframe |
Baseline and 42 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of subjects that experienced Clinical Worsening | ||||||||||||||
End point description |
Number of subjects 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.
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End point type |
Secondary
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End point timeframe |
Up to 42 months
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of subjects With a Change in WHO Functional Class | ||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline and 42 months
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From baseline to 30 days after study treatment discontinuation, up to 42 months.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Beraprost Sodium
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Reporting group description |
Beraprost Sodium Modified Release Tablet, 60 micrograms(mcg), twice a day dosing | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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13 Oct 2011 |
Amendment 1 dated 13 October 2011 (USA, Belgium, Romania): Revised to extend the calendar end date to allow ongoing subjects to continue to receive BPS-MR until
31 December 2013 or Lung LLC discontinues the project. A further administrative revision was applied to reflect the change of the Sponsor name from Lung Rx to Lung LLC. |
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25 Jun 2012 |
Amendment 2 dated 25 June 2012 (USA, Belgium, Romania): Revised to include an optional substudy investigating the safety, tolerability, and pharmacokinetics of BPS-MR tablets
administered four times daily (QID). An additional revision was applied to extend the calendar end date to allow ongoing subjects to receive BPS-MR until 31 December 2014 or
Lung LLC discontinues the project. Revisions were made to update the status of recently completed studies |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
