Trial Outcomes & Findings for An Open-Label Extension of BPS-MR-PAH-201 in Pulmonary Arterial Hypertension (PAH) Patients (NCT NCT00792571)

NCT ID: NCT00792571

Last Updated: 2019-12-26

Results Overview

A treatment-emergent adverse event (TEAEs) is defined as an event not present prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments. AEs occurring more than 3 days after the last day study drug is taken in the study will not be included in the statistical analyses or summaries (except for subjects with adverse events leading to study drug withdrawn). Only treatment-emergent adverse events occurring during the treatment period of the BPS-MR-PAH-202 study will be summarized. Any adverse event starting prior to the first dose of study drug will be excluded from the summary analyses and only presented in the data listings. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

Up to 56 months

Results posted on

2019-12-26

Participant Flow

Participants with pulmonary artery hypertension (PAH) who had completed lead in study BPS-MR-PAH-201 were enrolled in this study

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.

Participant milestones

Participant milestones
Measure
Beraprost Sodium
Beraprost Sodium Modified Release Tablets, 60mcg, b.i.d (twice a day dosing)
Overall Study
STARTED
18
Overall Study
COMPLETED
8
Overall Study
NOT COMPLETED
10

Reasons for withdrawal

Reasons for withdrawal
Measure
Beraprost Sodium
Beraprost Sodium Modified Release Tablets, 60mcg, b.i.d (twice a day dosing)
Overall Study
Death
1
Overall Study
Adverse Event
4
Overall Study
Withdrawal by Subject
1
Overall Study
Other
4

Baseline Characteristics

An Open-Label Extension of BPS-MR-PAH-201 in Pulmonary Arterial Hypertension (PAH) Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Beraprost Sodium
n=18 Participants
Beraprost Sodium Modified Release Tablets, 60mcg, b.i.d (twice a day dosing)
Age, Continuous
47.8 years
STANDARD_DEVIATION 13.16 • n=5 Participants
Sex: Female, Male
Female
14 Participants
n=5 Participants
Sex: Female, Male
Male
4 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
3 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
15 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
3 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
Race (NIH/OMB)
White
15 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Six-Minute Walk Distance
419.5 meters
STANDARD_DEVIATION 73.1 • n=5 Participants
Borg Dyspnea Score
3.4 score on a scale
STANDARD_DEVIATION 2.44 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 56 months

A treatment-emergent adverse event (TEAEs) is defined as an event not present prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments. AEs occurring more than 3 days after the last day study drug is taken in the study will not be included in the statistical analyses or summaries (except for subjects with adverse events leading to study drug withdrawn). Only treatment-emergent adverse events occurring during the treatment period of the BPS-MR-PAH-202 study will be summarized. Any adverse event starting prior to the first dose of study drug will be excluded from the summary analyses and only presented in the data listings. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure
Beraprost Sodium
n=18 Participants
Beraprost Sodium Modified Release Tablets, 60mcg, b.i.d (twice a day dosing)
Number of Participants Reporting at Least One Treatment-Emergent Adverse Event (TEAE)
18 Participants

PRIMARY outcome

Timeframe: Up to 56 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 participants with adverse events leading to study drug withdrawn). Only TEAEs that occurred during the treatment period of the BPS-MR-PAH-202 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. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure
Beraprost Sodium
n=18 Participants
Beraprost Sodium Modified Release Tablets, 60mcg, b.i.d (twice a day dosing)
Number of Treatment Emergent Adverse Events Reported During The Study
156 TEAEs

SECONDARY outcome

Timeframe: Baseline and 56 months

Population: Only participants with both a measurement at baseline and at the given visit are presented.

The area used for the Six Minute Walk Test (6MWT) was pre-measured at a minimum of 30 meters in length and at least 2 to 3 meters in width. There were no turns or significant curves to the 6-minute walk area. The length was marked with gradations to ensure the accurate measurement of the distance walked. The area was well ventilated with air temperature controlled at 20 to 23°C. Intermittent rest periods were allowed if the participant could no longer continue. If the participant needed to rest briefly, 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 simultaneously stopping the watch and then measured the distance walked. For the purposes of the 6MWT if a participant was assessed at Baseline using oxygen therapy, then all future 6MWT were conducted in the same manner. All efficacy results are descriptive; no statistical analysis was conducted.

Outcome measures

Outcome measures
Measure
Beraprost Sodium
n=11 Participants
Beraprost Sodium Modified Release Tablets, 60mcg, b.i.d (twice a day dosing)
Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at End of Study
10.55 meters
Standard Deviation 79.17

SECONDARY outcome

Timeframe: Baseline and 56 months

Population: Only participants with both a measurement at baseline and at the given visit are presented.

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-201. 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.

Outcome measures

Outcome measures
Measure
Beraprost Sodium
n=11 Participants
Beraprost Sodium Modified Release Tablets, 60mcg, b.i.d (twice a day dosing)
Change From Baseline in Borg Dyspnea Score at End of Study
-0.09 scores on a scale
Standard Deviation 2.84

SECONDARY outcome

Timeframe: Up to 56 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.

Outcome measures

Outcome measures
Measure
Beraprost Sodium
n=18 Participants
Beraprost Sodium Modified Release Tablets, 60mcg, b.i.d (twice a day dosing)
Number of Participants That Experienced Clinical Worsening During the Study
Death
1 Participants
Number of Participants That Experienced Clinical Worsening During the Study
New PAH Therapies
6 Participants
Number of Participants That Experienced Clinical Worsening During the Study
Transplantation or atrial septostomy
0 Participants
Number of Participants That Experienced Clinical Worsening During the Study
Hospitalization
0 Participants

SECONDARY outcome

Timeframe: Baseline and 56 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.

Outcome measures

Outcome measures
Measure
Beraprost Sodium
n=18 Participants
Beraprost Sodium Modified Release Tablets, 60mcg, b.i.d (twice a day dosing)
Number of Participants With a Change in WHO Functional Class
Improved: Change from Class III to Class II
1 Participants
Number of Participants With a Change in WHO Functional Class
No Change in Class
7 Participants
Number of Participants With a Change in WHO Functional Class
Deteriorated: Change from Class II to Class III
4 Participants
Number of Participants With a Change in WHO Functional Class
Not Reported
6 Participants

Adverse Events

Beraprost Sodium

Serious events: 7 serious events
Other events: 18 other events
Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure
Beraprost Sodium
n=18 participants at risk
Beraprost Sodium Modified Release Tablets, 60mcg, b.i.d (twice a day dosing)
Cardiac disorders
Right ventricular failure
11.1%
2/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Respiratory, thoracic and mediastinal disorders
Worsening Pulmonary arterial hypertension
11.1%
2/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Respiratory, thoracic and mediastinal disorders
Haemoptysis
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Lower respiratory tract infection
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Injury, poisoning and procedural complications
Post procedural haemorrhage
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Nervous system disorders
Presyncope
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Cardiac disorders
Atrial fibrillation
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Gastroenteritis viral
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Nervous system disorders
Syncope
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Cardiac disorders
Atrial flutter
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Bronchitis
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Surgical and medical procedures
Atrial septal defect repair
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.

Other adverse events

Other adverse events
Measure
Beraprost Sodium
n=18 participants at risk
Beraprost Sodium Modified Release Tablets, 60mcg, b.i.d (twice a day dosing)
Blood and lymphatic system disorders
Anaemia
16.7%
3/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Cardiac disorders
Arrhythmia
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Cardiac disorders
Atrial Fibrillation
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Cardiac disorders
Palpitations
22.2%
4/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Cardiac disorders
Right ventricular heave
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Ear and labyrinth disorders
Tinnitus
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Ear and labyrinth disorders
Vertigo
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Eye disorders
Astigmatism
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Eye disorders
Cataract
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Eye disorders
Eyelid Cyst
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Eye disorders
Myopia
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Eye disorders
Retinal Detachment
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Eye disorders
Retinal Tear
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Gastrointestinal disorders
Abdominal Discomfort
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Gastrointestinal disorders
Abdominal Pain
11.1%
2/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Gastrointestinal disorders
Abdominal Pain Upper
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Gastrointestinal disorders
Defaecation urgency
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Gastrointestinal disorders
Diarrhoea
16.7%
3/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Gastrointestinal disorders
Gastritis
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Gastrointestinal disorders
Irritable Bowel Syndrome
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Gastrointestinal disorders
Nausea
27.8%
5/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Gastrointestinal disorders
Rectal Hemmorrhage
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Gastrointestinal disorders
Vomiting
16.7%
3/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
General disorders
Asthenia
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
General disorders
Chest Pain
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
General disorders
Fatigue
11.1%
2/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
General disorders
Generalised oedema
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
General disorders
Pain
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
General disorders
Pyrexia
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Hepatobiliary disorders
Biliary Colic
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Hepatobiliary disorders
Cholecystitis
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Hepatobiliary disorders
Hepatitis acute
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Immune system disorders
Seasonal Allergy
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Bronchiolitis
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Bronchitis
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Cystitis
16.7%
3/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Fungal skin infection
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Herpes zoster
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Nasopharyngitis
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Pharyngitis
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Sinusitis
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Upper respiratory tract infection
33.3%
6/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Infections and infestations
Urinary Tract Infections
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Investigations
Liver Function Test Abnormal
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Investigations
Platelet Count Decreased
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Investigations
Urine analysis abnormal
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Investigations
Weight increased
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Metabolism and nutrition disorders
Fluid overload
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Metabolism and nutrition disorders
Hyperuricaemia
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Metabolism and nutrition disorders
Hypokalemia
11.1%
2/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Metabolism and nutrition disorders
Hypomagnesaemia
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Metabolism and nutrition disorders
Lactose Intolerance
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Musculoskeletal and connective tissue disorders
Arthralgia
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Musculoskeletal and connective tissue disorders
Muscle spasms
11.1%
2/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Musculoskeletal and connective tissue disorders
Muscle Tightness
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Musculoskeletal and connective tissue disorders
Muscle twitching
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Musculoskeletal and connective tissue disorders
Osteoporosis
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Musculoskeletal and connective tissue disorders
Pain in extremity
16.7%
3/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Musculoskeletal and connective tissue disorders
Pain in Jaw
16.7%
3/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Nervous system disorders
Dizziness
27.8%
5/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Nervous system disorders
Headache
33.3%
6/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Nervous system disorders
Hypoaesthesia
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Nervous system disorders
Presyncope
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Nervous system disorders
Restless Leg Syndrome
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Nervous system disorders
Syncope
11.1%
2/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Psychiatric disorders
Anxiety
11.1%
2/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Psychiatric disorders
Depression
11.1%
2/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Psychiatric disorders
Insomnia
16.7%
3/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Psychiatric disorders
Panic Attack
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Renal and urinary disorders
Haematuria
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Renal and urinary disorders
Pollakiuria
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Respiratory, thoracic and mediastinal disorders
Cough
16.7%
3/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Respiratory, thoracic and mediastinal disorders
Worsening pulmonary arterial hypertension
11.1%
2/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Respiratory, thoracic and mediastinal disorders
Dyspnoea
27.8%
5/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Respiratory, thoracic and mediastinal disorders
Nasal congestion
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Skin and subcutaneous tissue disorders
Rash
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Skin and subcutaneous tissue disorders
Urticaria
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Skin and subcutaneous tissue disorders
Skin Irritation
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Surgical and medical procedures
Tooth Extraction
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Vascular disorders
Flushing
33.3%
6/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Vascular disorders
Peripheral Coldness
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.
Vascular disorders
Vasculitis
5.6%
1/18 • From baseline to 30 days after study treatment discontinuation, up to 56 months.

Additional Information

Lung Biotechnology PBC Study Director

Lung Biotechnology PBC

Phone: 301-608-9292

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: GT60