Trial Outcomes & Findings for A Multi-Center, Open-Label, Multiple Dose, Dose Finding Study Exploring the Safety and Tolerability of Beraprost Sodium Modified Release in PAH Patients (NCT NCT00781885)

NCT ID: NCT00781885

Last Updated: 2020-06-09

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 19 participants
• Primary outcome timeframe: 10 Weeks
• Results posted on: 2020-06-09

Participant Flow

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

Measure	Beraprost Sodium Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Overall Study STARTED	19
Overall Study Received at Least 1 Dose of Study Drug	19
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Beraprost Sodium Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Overall Study Physician Decision	1

Baseline Characteristics

Only Participants with both a measurement at baseline and at the given visit are presented.

Baseline characteristics by cohort

Measure	Beraprost Sodium n=19 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Age, Continuous	47.6 years STANDARD_DEVIATION 12.85 • n=19 Participants
Sex: Female, Male Female	15 Participants n=19 Participants
Sex: Female, Male Male	4 Participants n=19 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=19 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=19 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=19 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=19 Participants
Race (NIH/OMB) Asian	3 Participants n=19 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=19 Participants
Race (NIH/OMB) Black or African American	0 Participants n=19 Participants
Race (NIH/OMB) White	16 Participants n=19 Participants
Race (NIH/OMB) More than one race	0 Participants n=19 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=19 Participants
Body Mass Index	30.4 kg/m^2 STANDARD_DEVIATION 7.57 • n=19 Participants
Respiratory Rate	18.5 Breaths per minute STANDARD_DEVIATION 1.61 • n=13 Participants • Only Participants with both a measurement at baseline and at the given visit are presented.
Temperature	36.5 degrees Celsius STANDARD_DEVIATION 0.35 • n=15 Participants • Only Participants with both a measurement at baseline and at the given visit are presented.
Systolic Blood Pressure (SBP)	118.1 mmHg STANDARD_DEVIATION 10.9 • n=19 Participants
Diastolic Blood Pressure (DBP)	76.8 mmHg STANDARD_DEVIATION 9.14 • n=19 Participants
Weight	81.7 kg STANDARD_DEVIATION 20.79 • n=19 Participants
Electrocardiogram (ECG) Intervals PR Interval	175.8 msec STANDARD_DEVIATION 28.26 • n=18 Participants • Only Participants with both a measurement at baseline and at the given visit are presented.
Electrocardiogram (ECG) Intervals QRS Interval	99.2 msec STANDARD_DEVIATION 14.7 • n=19 Participants • Only Participants with both a measurement at baseline and at the given visit are presented.
Electrocardiogram (ECG) Intervals QT Interval	396.5 msec STANDARD_DEVIATION 42.1 • n=19 Participants • Only Participants with both a measurement at baseline and at the given visit are presented.
Electrocardiogram (ECG) Intervals QTc Bazett	437.7 msec STANDARD_DEVIATION 27.4 • n=19 Participants • Only Participants with both a measurement at baseline and at the given visit are presented.
Electrocardiogram (ECG) Intervals QTc Friderica	422.9 msec STANDARD_DEVIATION 28.65 • n=19 Participants • Only Participants with both a measurement at baseline and at the given visit are presented.

PRIMARY outcome

Timeframe: 10 Weeks

Population: The Tolerability population includes all evaluable participants who achieved their MTD and had an End of Treatment visit.

Outcome measures

Measure	Beraprost Sodium n=18 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Maximum Tolerated Dose (MTD) of BPS-MR in Pulmonary Arterial Hypertension (PAH) Patients, Following Chronic, Twice-daily Administration. 120 mcg	2 Participants
Maximum Tolerated Dose (MTD) of BPS-MR in Pulmonary Arterial Hypertension (PAH) Patients, Following Chronic, Twice-daily Administration. 180 mcg	2 Participants
Maximum Tolerated Dose (MTD) of BPS-MR in Pulmonary Arterial Hypertension (PAH) Patients, Following Chronic, Twice-daily Administration. 240 mcg	3 Participants
Maximum Tolerated Dose (MTD) of BPS-MR in Pulmonary Arterial Hypertension (PAH) Patients, Following Chronic, Twice-daily Administration. 300 mcg	2 Participants
Maximum Tolerated Dose (MTD) of BPS-MR in Pulmonary Arterial Hypertension (PAH) Patients, Following Chronic, Twice-daily Administration. 420 mcg	1 Participants
Maximum Tolerated Dose (MTD) of BPS-MR in Pulmonary Arterial Hypertension (PAH) Patients, Following Chronic, Twice-daily Administration. 540 mcg	1 Participants
Maximum Tolerated Dose (MTD) of BPS-MR in Pulmonary Arterial Hypertension (PAH) Patients, Following Chronic, Twice-daily Administration. 600 mcg	7 Participants

SECONDARY outcome

Timeframe: 19 Weeks

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

Outcome measures

Measure	Beraprost Sodium n=19 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Number of Participants That Reported at Least One Treatment-Emergent Adverse Event (TEAE)	19 Participants

SECONDARY outcome

Timeframe: Baseline and 19 weeks

Population: Participants with both a baseline measurement and an End of Study measurement

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.

Outcome measures

Measure	Beraprost Sodium n=19 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Change in Body Mass Index (BMI) From Baseline to Week 19	-0.2 kilograms/meter^2 Standard Deviation 0.98

SECONDARY outcome

Timeframe: Baseline and 19 weeks

Population: Participants with both a baseline measurement and an End of Study measurement

Weight was assessed at each study visit and taken after five minutes of seated rest. Weight was measured in kilograms (kg).

Outcome measures

Measure	Beraprost Sodium n=19 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Change in Weight From Baseline to Week 19	-0.5 kg Standard Deviation 2.2

SECONDARY outcome

Timeframe: Baseline and 19 weeks

Population: Participants with both a baseline measurement and an End of Study measurement

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).

Outcome measures

Measure	Beraprost Sodium n=19 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Change in Heart Rate From Baseline to Week 19	0.7 Beats per Minute (BPM) Standard Deviation 12.3

SECONDARY outcome

Timeframe: Baseline and 19 weeks

Population: Participants with both a baseline measurement and an End of Study measurement

Body Temperature was assessed at each study visit and taken after five minutes of seated rest. Body temperature was measured in degrees Celsius (C).

Outcome measures

Measure	Beraprost Sodium n=19 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Change in Body Temperature From Baseline to Week 19	0.1 degrees Celsius Standard Deviation 0.45

SECONDARY outcome

Timeframe: Baseline and 19 weeks

Population: Participants with both a baseline measurement and an End of Study measurement

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).

Outcome measures

Measure	Beraprost Sodium n=19 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Change in Systolic Blood Pressure (SBP) From Baseline to Week 19	0.6 mmHg Standard Deviation 12.46

SECONDARY outcome

Timeframe: Baseline and 19 weeks

Population: Participants with both a baseline measurement and an End of Study measurement

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).

Outcome measures

Measure	Beraprost Sodium n=19 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Change in Diastolic Blood Pressure (DBP) From Baseline to Week 19	-2.5 mmHg Standard Deviation 7.5

SECONDARY outcome

Timeframe: Baseline and 19 weeks

Population: Participants with both a baseline measurement and an End of Study measurement

Respiratory Rate was assessed at each study visit and taken after five minutes of seated rest. Respiratory rate was measured in breaths per minute.

Outcome measures

Measure	Beraprost Sodium n=19 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Change in Respiratory Rate From Baseline to Week 19	0.2 Breaths per Minute Standard Deviation 1.24

SECONDARY outcome

Timeframe: Baseline and 19 weeks

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

Outcome measures

Measure	Beraprost Sodium n=19 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Change in Electrocardiogram Intervals From Baseline to Week 19 PR Interval	6.1 millisecond (msec) Standard Deviation 12.93
Change in Electrocardiogram Intervals From Baseline to Week 19 QRS Interval	-4.4 millisecond (msec) Standard Deviation 12.46
Change in Electrocardiogram Intervals From Baseline to Week 19 QT Interval	3.2 millisecond (msec) Standard Deviation 29.37
Change in Electrocardiogram Intervals From Baseline to Week 19 QTc Bazett	-2.5 millisecond (msec) Standard Deviation 20.05
Change in Electrocardiogram Intervals From Baseline to Week 19 QTc Friderica	-0.3 millisecond (msec) Standard Deviation 21.59

SECONDARY outcome

Timeframe: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 67

Population: 9 participants participated in the optional pharmacokinetic sub-study.

Apparent clearance is defined as plasma clearance divided by absolute bioavailability per kilogram of bodyweight.

Outcome measures

Measure	Beraprost Sodium n=9 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Apparent Clearance (CL/F) of BPS-MR	1.51 L/h/kg Standard Deviation 0.52

SECONDARY outcome

Timeframe: pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose on Day 67

Population: 9 participants participated in the optional pharmacokinetic sub-study.

Outcome measures

Measure	Beraprost Sodium n=9 Participants Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Apparent Volume of Distribution (Vz/F) of BPS-MR	43.6 Liters per kilogram (L/kg) Standard Deviation 68.4

Adverse Events

Beraprost Sodium

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Beraprost Sodium n=19 participants at risk Beraprost Sodium Modified Release (BPS-MR) 60 mcg tablets, administered orally, twice daily (BID). Doses were escalated by 1 tablet BID weekly, as tolerated, to a maximum dose of 600 mcg BID.
Cardiac disorders Palpitations	10.5% 2/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Cardiac disorders Cardiac Ventricular Disorder	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Ear and labyrinth disorders Ear Discomfort	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Gastrointestinal disorders Diarrhoea	57.9% 11/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Gastrointestinal disorders Nausea	31.6% 6/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Gastrointestinal disorders Stomach Discomfort	10.5% 2/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Gastrointestinal disorders Vomiting	10.5% 2/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Gastrointestinal disorders Abdominal Pain Upper	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Gastrointestinal disorders Defaecation Urgency	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Gastrointestinal disorders Flatulence	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
General disorders Pain	26.3% 5/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
General disorders Fatigue	15.8% 3/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
General disorders Pyrexia	10.5% 2/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
General disorders Chills	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
General disorders Oedema Peripheral	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Immune system disorders Drug Hypersensitivity	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Infections and infestations Bronchitis	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Infections and infestations Nasopharyngitis	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Infections and infestations Skin Infection	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Injury, poisoning and procedural complications Fall	10.5% 2/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Injury, poisoning and procedural complications Eye Injury	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Investigations Blood Bilirubin Increased	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Investigations Lymphocyte Count Increased	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Investigations Neutrophil Count Increased	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Metabolism and nutrition disorders Decreased Appetite	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Metabolism and nutrition disorders Fluid Overload	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Musculoskeletal and connective tissue disorders Pain In Extremity	36.8% 7/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Musculoskeletal and connective tissue disorders Pain In Jaw	36.8% 7/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Musculoskeletal and connective tissue disorders Neck Pain	10.5% 2/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Musculoskeletal and connective tissue disorders Back Pain	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Musculoskeletal and connective tissue disorders Juvenile Arthritis	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Nervous system disorders Headache	73.7% 14/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Nervous system disorders Dizziness	21.1% 4/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Respiratory, thoracic and mediastinal disorders Cough	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Skin and subcutaneous tissue disorders Cold Sweat	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Skin and subcutaneous tissue disorders Night Sweats	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Skin and subcutaneous tissue disorders Urticaria	5.3% 1/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Vascular disorders Flushing	36.8% 7/19 • From baseline to 30 days after study treatment discontinuation, up to 7 months.
Vascular disorders Hot Flush	10.5% 2/19 • From baseline to 30 days after study treatment discontinuation, up to 7 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