Trial Outcomes & Findings for Long-term Safety and Efficacy of Ralinepag in Pulmonary Arterial Hypertension (NCT NCT02279745)
NCT ID: NCT02279745
Last Updated: 2021-12-22
Results Overview
Pulmonary vascular resistance was collected by right heart catheterization (RHC).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
45 participants
Primary outcome timeframe
At 1 or 2 years after the subject enrolled into the study, pending their last RHC prior to Protocol Amendment 2.
Results posted on
2021-12-22
Participant Flow
Participant milestones
| Measure |
Oral Ralinepag
Ralinepag immediate-release (IR) capsules of 10, 20, 30, 40, and 100 mcg or extended-release (XR) tablets of 50, 250, and 400 mcg for oral administration were provided. The starting dose and titration schedule were determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003. Subjects in the placebo treatment group in Study APD811-003 underwent a dose titration period (up to 9 weeks) with ralinepag until a stable maximum tolerated dose (MTD) was reached.
Ralinepag: Active
|
|---|---|
|
Overall Study
STARTED
|
45
|
|
Overall Study
COMPLETED
|
25
|
|
Overall Study
NOT COMPLETED
|
20
|
Reasons for withdrawal
| Measure |
Oral Ralinepag
Ralinepag immediate-release (IR) capsules of 10, 20, 30, 40, and 100 mcg or extended-release (XR) tablets of 50, 250, and 400 mcg for oral administration were provided. The starting dose and titration schedule were determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003. Subjects in the placebo treatment group in Study APD811-003 underwent a dose titration period (up to 9 weeks) with ralinepag until a stable maximum tolerated dose (MTD) was reached.
Ralinepag: Active
|
|---|---|
|
Overall Study
Adverse Event
|
7
|
|
Overall Study
Death
|
6
|
|
Overall Study
Clinical Worsening as Defined by Protocol
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Pregnancy
|
1
|
|
Overall Study
Study Non-compliance
|
1
|
|
Overall Study
Did Not Transition to Study ROR-PH-303
|
1
|
Baseline Characteristics
Long-term Safety and Efficacy of Ralinepag in Pulmonary Arterial Hypertension
Baseline characteristics by cohort
| Measure |
Oral Ralinepag
n=45 Participants
Ralinepag IR capsules of 10, 20, 30, 40, and 100 mcg or XR tablets of 50, 250, and 400 mcg for oral administration were provided. The starting dose and titration schedule were determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003. Subjects in the placebo treatment group in Study APD811-003 underwent a dose titration period (up to 9 weeks) with ralinepag until a stable MTD was reached.
Ralinepag: Active
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
39 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=5 Participants
|
|
Age, Continuous
|
51.0 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
44 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
|
1 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
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
42 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Time Since Pulmonary Arterial Hypertension (PAH) Diagnosis
|
2.30 years
n=5 Participants
|
|
Etiology of PAH
Idiopathic PAH
|
23 Participants
n=5 Participants
|
|
Etiology of PAH
Heritable PAH
|
4 Participants
n=5 Participants
|
|
Etiology of PAH
Drug or Toxin Induced PAH
|
2 Participants
n=5 Participants
|
|
Etiology of PAH
PAH Associated with Other Disease
|
16 Participants
n=5 Participants
|
|
6-Minute Walk Distance (6MWD) at Baseline
|
425.0 meters
n=5 Participants
|
|
World Health Organization (WHO) Functional Class at Baseline
I
|
3 Participants
n=5 Participants
|
|
World Health Organization (WHO) Functional Class at Baseline
II
|
32 Participants
n=5 Participants
|
|
World Health Organization (WHO) Functional Class at Baseline
III
|
10 Participants
n=5 Participants
|
|
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) at Baseline
|
357.60 pg/mL
n=5 Participants
|
PRIMARY outcome
Timeframe: At 1 or 2 years after the subject enrolled into the study, pending their last RHC prior to Protocol Amendment 2.Population: The number of subjects varied at post-baseline assessments due to the timing of the assessments relative to the subjects' time on study drug.
Pulmonary vascular resistance was collected by right heart catheterization (RHC).
Outcome measures
| Measure |
Oral Ralinepag
n=31 Participants
Ralinepag IR capsules of 10, 20, 30, 40, and 100 mcg or XR tablets of 50, 250, and 400 mcg for oral administration were provided. The starting dose and titration schedule were determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003. Subjects in the placebo treatment group in Study APD811-003 underwent a dose titration period (up to 9 weeks) with ralinepag until a stable MTD was reached.
Ralinepag: Active
|
|---|---|
|
Change From Baseline in Pulmonary Vascular Resistance
|
-52.2 dynes.sec/cm5
Interval -573.0 to 846.0
|
PRIMARY outcome
Timeframe: At 1 or 2 years after the subject enrolled into the study, pending their last RHC prior to Protocol Amendment 2.Population: The number of subjects varied at post-baseline assessments due to the timing of the assessments relative to the subjects' time on study drug.
Cardiac output was collected by right heart catheterization (RHC).
Outcome measures
| Measure |
Oral Ralinepag
n=31 Participants
Ralinepag IR capsules of 10, 20, 30, 40, and 100 mcg or XR tablets of 50, 250, and 400 mcg for oral administration were provided. The starting dose and titration schedule were determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003. Subjects in the placebo treatment group in Study APD811-003 underwent a dose titration period (up to 9 weeks) with ralinepag until a stable MTD was reached.
Ralinepag: Active
|
|---|---|
|
Change From Baseline in Cardiac Output
|
-0.0 L/min
Interval -2.0 to 5.0
|
PRIMARY outcome
Timeframe: At 1 or 2 years after the subject enrolled into the study, pending their last RHC prior to Protocol Amendment 2.Population: The number of subjects varied at post-baseline assessments due to the timing of the assessments relative to the subjects' time on study drug.
Cardiac index was collected by right heart catheterization (RHC).
Outcome measures
| Measure |
Oral Ralinepag
n=31 Participants
Ralinepag IR capsules of 10, 20, 30, 40, and 100 mcg or XR tablets of 50, 250, and 400 mcg for oral administration were provided. The starting dose and titration schedule were determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003. Subjects in the placebo treatment group in Study APD811-003 underwent a dose titration period (up to 9 weeks) with ralinepag until a stable MTD was reached.
Ralinepag: Active
|
|---|---|
|
Change From Baseline in Cardiac Index
|
0.0 L/min/m2
Interval -1.0 to 3.0
|
PRIMARY outcome
Timeframe: At 1 or 2 years after the subject enrolled into the study, pending their last RHC prior to Protocol Amendment 2.Population: The number of subjects varied at post-baseline assessments due to the timing of the assessments relative to the subjects' time on study drug.
Mean pulmonary arterial pressure was collected by right heart catheterization (RHC).
Outcome measures
| Measure |
Oral Ralinepag
n=31 Participants
Ralinepag IR capsules of 10, 20, 30, 40, and 100 mcg or XR tablets of 50, 250, and 400 mcg for oral administration were provided. The starting dose and titration schedule were determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003. Subjects in the placebo treatment group in Study APD811-003 underwent a dose titration period (up to 9 weeks) with ralinepag until a stable MTD was reached.
Ralinepag: Active
|
|---|---|
|
Change From Baseline in Mean Pulmonary Arterial Pressure
|
-2.0 mmHg
Interval -23.0 to 18.0
|
SECONDARY outcome
Timeframe: From Baseline to 28 days following discontinuation of study drug, up to 235 weeks.Population: Safety Population
Clinical worsening events were defined as death, or onset of a treatment-emergent adverse event (AE) with a fatal outcome occurring ≤14 days after treatment discontinuation; hospitalization for worsening PAH, heart-lung or lung transplant, or atrial septostomy; necessity of addition (or dose change) of any prostacyclin/prostacyclin analogue, phosphodiesterase type 5 inhibitor (PDE5-I) or soluble guanylate cyclase (sGC), or endothelin receptor antagonist (ERA); and the combined occurrence of a decrease in 6-Minute Walk Distance (6MWD) by at least 20% from Baseline, confirmed on two 6-Minute Walk Tests (6MWTs) on different days; worsening in WHO/New York Heart Association (NYHA) Functional Class (FC) from Baseline; and appearance of or worsening of signs/symptoms of right heart failure that did not respond to optimized oral diuretic therapy.
Outcome measures
| Measure |
Oral Ralinepag
n=45 Participants
Ralinepag IR capsules of 10, 20, 30, 40, and 100 mcg or XR tablets of 50, 250, and 400 mcg for oral administration were provided. The starting dose and titration schedule were determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003. Subjects in the placebo treatment group in Study APD811-003 underwent a dose titration period (up to 9 weeks) with ralinepag until a stable MTD was reached.
Ralinepag: Active
|
|---|---|
|
Time From Randomization to the First Protocol-defined Clinical Worsening Event
|
56.50 weeks
Interval 16.9 to 136.6
|
SECONDARY outcome
Timeframe: From Baseline to discontinuation of study drug, up to 235 weeksPopulation: The number of subjects varied from month to month based on total study population at the time of each visit.
6MWD was measured at Baseline (prior to starting study drug) and every 3 months thereafter including the End of Study Visit.
Outcome measures
| Measure |
Oral Ralinepag
n=45 Participants
Ralinepag IR capsules of 10, 20, 30, 40, and 100 mcg or XR tablets of 50, 250, and 400 mcg for oral administration were provided. The starting dose and titration schedule were determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003. Subjects in the placebo treatment group in Study APD811-003 underwent a dose titration period (up to 9 weeks) with ralinepag until a stable MTD was reached.
Ralinepag: Active
|
|---|---|
|
Change From Baseline in 6MWD
Month 33
|
17.0 meters
Interval -80.0 to 237.0
|
|
Change From Baseline in 6MWD
Month 3
|
20.9 meters
Interval -75.0 to 115.0
|
|
Change From Baseline in 6MWD
Month 6
|
17.6 meters
Interval -118.0 to 90.0
|
|
Change From Baseline in 6MWD
Month 9
|
22.8 meters
Interval -88.0 to 140.0
|
|
Change From Baseline in 6MWD
Month 12
|
28.5 meters
Interval -126.0 to 138.0
|
|
Change From Baseline in 6MWD
Month 15
|
16.2 meters
Interval -91.0 to 143.0
|
|
Change From Baseline in 6MWD
Month 18
|
16.0 meters
Interval -100.0 to 179.0
|
|
Change From Baseline in 6MWD
Month 21
|
32.0 meters
Interval -162.0 to 175.0
|
|
Change From Baseline in 6MWD
Month 24
|
41.0 meters
Interval -111.0 to 237.0
|
|
Change From Baseline in 6MWD
Month 27
|
38.5 meters
Interval -141.0 to 239.0
|
|
Change From Baseline in 6MWD
Month 30
|
21.0 meters
Interval -159.0 to 267.0
|
|
Change From Baseline in 6MWD
Month 36
|
47.0 meters
Interval -60.0 to 123.0
|
|
Change From Baseline in 6MWD
Month 39
|
24.0 meters
Interval -180.0 to 105.0
|
|
Change From Baseline in 6MWD
Month 42
|
53.0 meters
Interval -162.0 to 112.0
|
|
Change From Baseline in 6MWD
Month 45
|
20.5 meters
Interval -160.0 to 100.0
|
|
Change From Baseline in 6MWD
Month 48
|
1.0 meters
Interval -160.0 to 57.0
|
|
Change From Baseline in 6MWD
Month 51
|
-120 meters
Interval -120.0 to -120.0
|
|
Change From Baseline in 6MWD
End of Study (Time of Discontinuation of Study by Sponsor)
|
37.0 meters
Interval -327.0 to 170.0
|
SECONDARY outcome
Timeframe: From Baseline to 28 days following discontinuation of study drug, up to 235 weeksPopulation: The number of subjects varied from month to month based on total study population at the time of each visit.
WHO/NYHA FC was measured at Baseline (prior to starting study drug) and every 3 months thereafter including at the End of Study and 28-Day Follow-up Visits. FC recorded as I, II, III, or IV based on the following: I: PH but without limitation of physical activity; physical activity without undue dyspnea or fatigue, chest pain or near syncope. II: PH with slight limitation of physical activity; physical activity causes undue dyspnea or fatigue, chest pain or near syncope. III: PH with marked limitation of physical activity; less than ordinary activity causes undue dyspnea or fatigue, chest pain or near syncope. IV: PH with inability to carry out any physical activity without symptoms. Signs of right heart failure. Dyspnea and/or fatigue at rest. Discomfort is increased by any physical activity.
Outcome measures
| Measure |
Oral Ralinepag
n=45 Participants
Ralinepag IR capsules of 10, 20, 30, 40, and 100 mcg or XR tablets of 50, 250, and 400 mcg for oral administration were provided. The starting dose and titration schedule were determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003. Subjects in the placebo treatment group in Study APD811-003 underwent a dose titration period (up to 9 weeks) with ralinepag until a stable MTD was reached.
Ralinepag: Active
|
|---|---|
|
Change From Baseline in WHO/NYHA FC
Month 9 · Deteriorated
|
3 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 18 · No Change
|
31 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 18 · Deteriorated
|
1 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 21 · Improved
|
0 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 21 · No Change
|
30 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 21 · Deteriorated
|
4 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 33 · Improved
|
1 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 33 · No Change
|
21 Participants
|
|
Change From Baseline in WHO/NYHA FC
End of Study (Time of Discontinuation of Study by Sponsor) · No Change
|
29 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 3 · Improved
|
1 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 3 · No Change
|
43 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 3 · Deteriorated
|
0 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 6 · Improved
|
2 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 6 · No Change
|
37 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 6 · Deteriorated
|
3 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 9 · Improved
|
1 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 9 · No Change
|
36 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 12 · Improved
|
0 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 12 · No Change
|
37 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 12 · Deteriorated
|
2 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 15 · Improved
|
0 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 15 · No Change
|
33 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 15 · Deteriorated
|
3 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 18 · Improved
|
2 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 24 · Improved
|
2 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 24 · No Change
|
28 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 24 · Deteriorated
|
3 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 27 · Improved
|
2 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 27 · No Change
|
28 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 27 · Deteriorated
|
2 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 30 · Improved
|
2 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 30 · No Change
|
23 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 30 · Deteriorated
|
4 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 33 · Deteriorated
|
3 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 36 · Improved
|
1 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 36 · No Change
|
13 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 36 · Deteriorated
|
2 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 39 · Improved
|
1 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 39 · No Change
|
11 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 39 · Deteriorated
|
1 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 42 · Improved
|
0 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 42 · No Change
|
10 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 42 · Deteriorated
|
1 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 45 · Improved
|
1 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 45 · No Change
|
6 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 45 · Deteriorated
|
1 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 48 · Improved
|
1 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 48 · No Change
|
4 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 48 · Deteriorated
|
0 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 51 · Improved
|
0 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 51 · No Change
|
2 Participants
|
|
Change From Baseline in WHO/NYHA FC
Month 51 · Deteriorated
|
0 Participants
|
|
Change From Baseline in WHO/NYHA FC
End of Study (Time of Discontinuation of Study by Sponsor) · Improved
|
2 Participants
|
|
Change From Baseline in WHO/NYHA FC
End of Study (Time of Discontinuation of Study by Sponsor) · Deteriorated
|
4 Participants
|
Adverse Events
Oral Ralinepag
Serious events: 21 serious events
Other events: 45 other events
Deaths: 8 deaths
Serious adverse events
| Measure |
Oral Ralinepag
n=45 participants at risk
Ralinepag IR capsules of 10, 20, 30, 40, and 100 mcg or XR tablets of 50, 250, and 400 mcg for oral administration were provided. The starting dose and titration schedule were determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003. Subjects in the placebo treatment group in Study APD811-003 underwent a dose titration period (up to 9 weeks) with ralinepag until a stable MTD was reached.
Ralinepag: Active
There was only 1 active dose group in this open-label study (oral ralinepag). Subjects included in this study received ralinepag and completed previous Study APD811-003, or received placebo and discontinued Study APD811-003 due to clinical worsening. All subjects enrolled in Study APD811-007 received open-label treatment with oral ralinepag IR or XR formulations. The starting dose and titration schedule were individually determined in accordance with the starting dose and titration schedule optimized during Study APD811 003. Adjustments in the dose and titration schedule were made according to subject tolerability.
|
|---|---|
|
Cardiac disorders
Right ventricular failure
|
13.3%
6/45 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Blood and lymphatic system disorders
Anaemia
|
4.4%
2/45 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Cardiac disorders
Cardiac arrest
|
4.4%
2/45 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Gastrointestinal disorders
Haematemesis
|
4.4%
2/45 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Gastrointestinal disorders
Abdominal distension
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Gastrointestinal disorders
Abdominal pain
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Renal and urinary disorders
Acute kidney injury
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Cardiac disorders
Arrhythmia supraventricular
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
General disorders
Asthenia
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Cardiac disorders
Atrial fibrillation
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
Brain abscess
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer in situ
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
COVID-19
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
COVID-19 pneumonia
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Cardiac disorders
Cardiac failure
|
4.4%
2/45 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Cardiac disorders
Cardiac failure congestive
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Cardiac disorders
Cardiopulmonary failure
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
General disorders
Chest pain
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
Clostridium difficile infection
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
Device related sepsis
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
General disorders
Drug withdrawal syndrome
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Nervous system disorders
Epilepsy
|
2.2%
1/45 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Injury, poisoning and procedural complications
Foot fracture
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
Gastroenteritis viral
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Injury, poisoning and procedural complications
Head injury
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Vascular disorders
Hypotension
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
General disorders
Multiple organ dysfunction syndrome
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
General disorders
Non-cardiac chest pain
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
2.2%
1/45 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
Pneumonia
|
4.4%
2/45 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary infarction
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Nervous system disorders
Syncope
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Gastrointestinal disorders
Varices oesophageal
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Cardiac disorders
Atrial flutter
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Vascular disorders
Deep vein thrombosis
|
2.2%
1/45 • Number of events 1 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary arterial hypertension
|
4.4%
2/45 • Number of events 2 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
Other adverse events
| Measure |
Oral Ralinepag
n=45 participants at risk
Ralinepag IR capsules of 10, 20, 30, 40, and 100 mcg or XR tablets of 50, 250, and 400 mcg for oral administration were provided. The starting dose and titration schedule were determined for each subject in accordance with the starting dose and titration schedule optimized from Study APD811-003. Subjects in the placebo treatment group in Study APD811-003 underwent a dose titration period (up to 9 weeks) with ralinepag until a stable MTD was reached.
Ralinepag: Active
There was only 1 active dose group in this open-label study (oral ralinepag). Subjects included in this study received ralinepag and completed previous Study APD811-003, or received placebo and discontinued Study APD811-003 due to clinical worsening. All subjects enrolled in Study APD811-007 received open-label treatment with oral ralinepag IR or XR formulations. The starting dose and titration schedule were individually determined in accordance with the starting dose and titration schedule optimized during Study APD811 003. Adjustments in the dose and titration schedule were made according to subject tolerability.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
17.8%
8/45 • Number of events 12 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Cardiac disorders
Palpitations
|
11.1%
5/45 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Cardiac disorders
Right ventricular failure
|
13.3%
6/45 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Cardiac disorders
Cardiac failure
|
8.9%
4/45 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Gastrointestinal disorders
Diarrhoea
|
37.8%
17/45 • Number of events 27 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Gastrointestinal disorders
Nausea
|
31.1%
14/45 • Number of events 25 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Gastrointestinal disorders
Vomiting
|
11.1%
5/45 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
3/45 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
General disorders
Fatigue
|
15.6%
7/45 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
General disorders
Oedema peripheral
|
8.9%
4/45 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
General disorders
Non-cardiac chest pain
|
6.7%
3/45 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
Influenza
|
6.7%
3/45 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
Pneumonia
|
8.9%
4/45 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
Bronchitis
|
6.7%
3/45 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
Lower respiratory tract infection
|
8.9%
4/45 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
Urinary tract infection
|
8.9%
4/45 • Number of events 7 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
Respiratory tract infection
|
6.7%
3/45 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Infections and infestations
Upper respiratory tract infection
|
11.1%
5/45 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Investigations
N-terminal prohormone brain natriuretic peptide increased
|
13.3%
6/45 • Number of events 10 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
6.7%
3/45 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
6.7%
3/45 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Metabolism and nutrition disorders
Iron deficiency
|
11.1%
5/45 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
33.3%
15/45 • Number of events 20 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
26.7%
12/45 • Number of events 23 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
15.6%
7/45 • Number of events 8 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
15.6%
7/45 • Number of events 13 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.7%
3/45 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
11.1%
5/45 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Nervous system disorders
Headache
|
64.4%
29/45 • Number of events 60 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Nervous system disorders
Dizziness
|
17.8%
8/45 • Number of events 15 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Nervous system disorders
Syncope
|
6.7%
3/45 • Number of events 5 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Nervous system disorders
Presyncope
|
6.7%
3/45 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Psychiatric disorders
Anxiety
|
6.7%
3/45 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
8.9%
4/45 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.9%
4/45 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary arterial hypertension
|
6.7%
3/45 • Number of events 3 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.9%
4/45 • Number of events 4 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Vascular disorders
Flushing
|
26.7%
12/45 • Number of events 16 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
|
Vascular disorders
Hypotension
|
13.3%
6/45 • Number of events 6 • AEs were recorded for each subject throughout the course of the study from Baseline to 28 days following discontinuation of study drug (up to 235 weeks).
Monitoring of AEs was continued up to 30 days after cessation of study drug administration. If an AE was not resolved or stabilized within 30 days, the Sponsor in consultation with the Investigator decided whether to continue to monitor the AE or close out the event in the database if no further follow-up was necessary. Serious adverse events (SAEs) were monitored until resolution or stabilization.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60