Pulmonary Arterial Hypertension
Conditions
Keywords
Right ventricle, Reverse remodeling, Magnetic resonance Imaging
Brief summary
The purpose of the study is to assess the effects of selexipag on right ventricular (RV) function in participants with Pulmonary arterial hypertension (PAH).
Interventions
DRUGJNJ-67896049
Participants will receive tablets at a starting dose of 200 mcg on Day 1. Dose will be up-titrated from Day 1 to the end of Week 12 (Day 84) to determine individual maintenance dose (IMD). Then, participants will receive JNJ-67896049 tablets at their IMD from Week 13 to Week 52.
Sponsors
Actelion
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* World health organization functional class (WHO FC) II or III. Enrollment will be stratified by WHO FC II or III. Proportion of participants with WHO FC II and WHO FC III are expected to be approximately 40 percent (%) and 60%, respectively * Pulmonary arterial hypertension (PAH) etiology belonging to one of the following groups according to 6th world symposium of pulmonary hypertension (WSPH) classification: a) Idiopathic PAH, b) Heritable PAH, c) Drugs or toxins induced d) PAH associated with connective tissue disease, e) PAH associated with congenital heart disease, with simple systemic-to-pulmonary shunt at least 1 year after surgical repair * Patients already receiving PAH-specific oral mono or dual therapy (that is, phosphodiesterase type 5 inhibitors \[PDE-5i\] or soluble guanylate cyclase stimulators \[sGCs\] and/or endothelin receptor antagonist \[ERA\]) or patients who are not candidates for these therapies * N-terminal-pro-hormone brain natriuretic peptide (NT-proBNP) greater than or equal to (\>=) 300 nanograms per liter (ng/L) (greater than or equal to \[\>=\] 300 picograms per milliliter \[pg/mL\]; \>=35.5 picomoles per liter \[pmol/L\]) at screening * Women of childbearing potential must meet the following criteria: a) Have a negative serum pregnancy test during screening and a negative urine pregnancy test on Day 1, b) Agree to use acceptable methods of contraception from Day 1 to at least 30 days after study intervention discontinuation, c) If only using hormonal contraception, have used it for at least 1 month (30 days) before Day 1, and d) Agree to perform monthly pregnancy tests to at least 30 days after study intervention discontinuation * 6-minute walking distance (6MWD) \>=150 meter (m) during screening period
Exclusion criteria
* Prior use of Prostacyclin (IP)-receptor agonist, prostacyclin, or prostacyclin analog. Use of such treatments for vasoreactivity testing is not exclusionary; intermittent use of such treatments for digital ulcers or Raynaud's phenomenon is not exclusionary if stopped \> 6 months (180 days) prior to Day 1 * Treatment with strong inhibitors of CYP2C8 (example, gemfibrozil) within 4 weeks (28 days) prior to Day 1 * Treatment with another investigational drug planned or taken within 12 weeks (84 days) prior to Day 1 * Severe coronary heart disease or unstable angina * Cerebrovascular events (example, transient ischemic attack, stroke) within 3 months (90 days) prior to Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI) | Baseline, Week 26 | Change from baseline to Week 26 in RVSV assessed by pulmonary artery flow MRI was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 26 in Right Ventricular End-Diastolic Volume (RVEDV) Assessed by MRI | Baseline, Week 26 | Change from baseline to Week 26 in RVEDV assessed by MRI was reported. |
| Change From Baseline to Week 26 in Right Ventricular End-Systolic Volume (RVESV) Assessed by MRI | Baseline, Week 26 | Change from baseline to Week 26 in RVESV assessed by MRI was reported. |
| Change From Baseline to Week 26 in Right Ventricular Ejection Fraction (RVEF) Assessed by MRI | Baseline, Week 26 | Change from baseline to Week 26 in RVEF assessed by MRI was reported. RVEF was the fraction of the end-diastolic volume (EDV) that is ejected out of right ventricle with each contraction. EDV is the volume of blood within a ventricle immediately before a contraction. |
| Change From Baseline to Week 26 in Right Ventricular (RV) Mass Index Assessed by MRI | Baseline, Week 26 | Change from baseline to Week 26 in RV mass index assessed by MRI was reported. |
| Change From Baseline to Week 26 in Right Ventricular Global Longitudinal Strain (RVGLS) Assessed by MRI | Baseline, Week 26 | Change in RVGLS was a measure of longitudinal percent change in length of endocardium at Week 26 from baseline length assessed by MRI. |
| Number of Participants With Change From Baseline to Week 26 in World Health Organization (WHO) Functional Class | Baseline, Week 26 | WHO functional classification for PAH ranged from Class I (no limitation in physical activity, ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope), Class II (slight limitation of physical activity, ordinary physical activity cause undue dyspnea or fatigue, chest pain or near syncope), Class III (marked limitation of physical activity, less than ordinary activity cause undue dyspnea or fatigue, chest pain or near syncope) and Class IV (cannot perform a physical activity without any symptoms, dyspnea and/or fatigue may even be present at rest). Change from baseline in WHO functional class was classified into Improved, No change and Worsened. Improvement =reduction in functional class; worsened =increase in functional class; and no change = no change in functional class. |
| Change From Baseline to Week 26 in N-terminal-Pro-Hormone Brain Natriuretic Peptide (NT-proBNP) | Baseline, Week 26 | NT pro-BNP is a cardiac biomarker that is released in the blood in response to changes in the pressure inside of the heart. Levels go up when heart failure develops or gets worse, and levels go down when heart failure is stable or improves. This biomarker helps to measure the changes in the severity of heart failure over time in response to therapy. |
| Change From Baseline to Week 26 in 6-Minute Walk Distance (6MWD) | Baseline, Week 26 | 6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to 3 days after last dose of study drug (up to 52 weeks and 3 days that is 367 days) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product. Any AE occurring at or after the initial administration of study intervention up to 3 days after last dose of study intervention was considered as treatment-emergent. |
| Number of Participants With Adverse Events (AEs) Leading to Premature Discontinuation of Study Drug | Day 1 up to last dose of study drug (up to Week 52) | Number of participants with AEs leading to premature discontinuation of study drug were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. |
| Number of Participants With Adverse Events of Special Interest (AESI) | Day 1 up to 3 days after last dose of study drug (up to 52 weeks and 3 days that is 367 days) | Number of participants with AESI were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AESI were anaemia, bleeding events, gastrointestinal disturbances denoting intestinal intussusception (manifested as ileus or obstruction), hyperthyroidism, hypotension, light-dependent non-melanoma skin malignancies, major adverse cardiovascular events (MACE), medication errors, ophthalmological effects associated to retinal vascular system, pregnancy, pulmonary venoocclusive disease associated with pulmonary oedema, renal function impairment / acute renal failure. |
| Number of Participants With Treatment-Emergent Marked Laboratory Abnormalities | Day 1 up to 3 days after last dose of study drug (up to 52 weeks and 3 days that is 367 days) | Number of participants with treatment-emergent marked laboratory abnormalities in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, creatinine, sodium, potassium, hemoglobin, hematocrit; EVF; PCV (male), hematocrit; EVF; PCV (female), platelets (assuming no platelet cluster), leukocytes; white blood cells, Neutrophils (Abs), Eosinophils (Abs), lymphocytes (Abs) were reported. Abnormalities that occurred after study treatment start and up to 3 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Treatment-emergent marked laboratory abnormalities were determined at the investigator's discretion. |
| Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 8 Variables | Baseline, Week 26 | The risk score is derived for each participant considering the following non-invasive low-risk criteria among the 8 variables: absence of clinical signs of right heart failure, absence of symptoms progression, absence of syncope, WHO FC I-II, 6MWD greater than (\>) 440 meter, NT-proBNP less than (\<) 300 ng/L, Right atrial (RA) area \<18 centimeter square (cm\^2) as determined by echocardiography (Echo), absence of pericardial effusion, as determined by Echo. Number of low-risk criteria at baseline and Week 26 constitutes risk score and were derived for each participant by adding '1' for each of above criteria met. Number of low-risk criteria among the 8 variables for each participant can vary from 0 (worse participants) to 8 (healthier participants). Higher score indicated healthier participants. |
| Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 3 Variables | Baseline, Week 26 | The risk score is derived for each participant considering the following non-invasive low-risk criteria among the 3 variables: WHO FC I-II, 6MWD \>440 m, NT-proBNP \< 300 ng/L. Number of low-risk criteria at baseline and Week 26 constitutes risk score and were derived for each participant by adding '1' for each of above criteria met. Number of low-risk criteria among the 3 variables for each participant can vary from 0 (worse participants) to 3 (healthier participants). Higher score indicated healthier participants. |
Countries
Argentina, Brazil, France, Germany, Hong Kong, Israel, Malaysia, Netherlands, Russia, Saudi Arabia, Singapore, South Korea, United Arab Emirates, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Selexipag Participants with pulmonary arterial hypertension (PAH) received a 200 microgram (mcg) selexipag tablet orally on the evening of Day 1, followed by twice-daily dosing starting from Day 2. The dose of selexipag was increased by 200 mcg each week to allow each participant to reach their individual maximum dose (iMD), up to 1600 mcg twice daily, by the end of Week 12. From Week 13 onwards, participants received their iMD of 1600 mcg selexipag tablets orally twice daily until Week 52. Participants were then followed for safety up to 30 days after the last dose of selexipag. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study terminated by sponsor | 4 |
Baseline characteristics
| Characteristic | Selexipag |
|---|---|
| Age, Continuous | 42.2 years STANDARD_DEVIATION 13.28 |
| Age, Customized 85 years and over | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants |
| Age, Customized Adults (18-64 years) | 9 Participants |
| Age, Customized Children (2-11 years) | 0 Participants |
| Age, Customized From 65-84 years | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants |
| Age, Customized In utero | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 1 / 9 |
Outcome results
Primary
Change From Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI)
Change from baseline to Week 26 in RVSV assessed by pulmonary artery flow MRI was reported.
Time frame: Baseline, Week 26
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and n (Number Analyzed) signifies participants evaluable for specified rows. As pre-specified in the statistical analysis plan (SAP), participant wise data was collected and reported due to very limited number of participants enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI) | Participant 1 | 38.35 Milliliter (mL) |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI) | Participant 2 | -1.53 Milliliter (mL) |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI) | Participant 3 | 16.53 Milliliter (mL) |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI) | Participant 4 | 11 Milliliter (mL) |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI) | Participant 5 | 27.2 Milliliter (mL) |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Stroke Volume (RVSV) Assessed by Pulmonary Artery Flow Magnetic Resonance Imaging (MRI) | Participant 6 | 14.07 Milliliter (mL) |
Secondary
Change From Baseline to Week 26 in 6-Minute Walk Distance (6MWD)
6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.
Time frame: Baseline, Week 26
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and n (Number Analyzed) signifies participants evaluable for specified rows. As pre-specified in the SAP, participant wise data was collected and reported due to very limited number of participants enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 26 in 6-Minute Walk Distance (6MWD) | Participant 1 | -72 Meter |
| Selexipag | Change From Baseline to Week 26 in 6-Minute Walk Distance (6MWD) | Participant 2 | 0 Meter |
| Selexipag | Change From Baseline to Week 26 in 6-Minute Walk Distance (6MWD) | Participant 3 | 275 Meter |
| Selexipag | Change From Baseline to Week 26 in 6-Minute Walk Distance (6MWD) | Participant 4 | 14 Meter |
| Selexipag | Change From Baseline to Week 26 in 6-Minute Walk Distance (6MWD) | Participant 5 | 17 Meter |
| Selexipag | Change From Baseline to Week 26 in 6-Minute Walk Distance (6MWD) | Participant 6 | 16 Meter |
Secondary
Change From Baseline to Week 26 in N-terminal-Pro-Hormone Brain Natriuretic Peptide (NT-proBNP)
NT pro-BNP is a cardiac biomarker that is released in the blood in response to changes in the pressure inside of the heart. Levels go up when heart failure develops or gets worse, and levels go down when heart failure is stable or improves. This biomarker helps to measure the changes in the severity of heart failure over time in response to therapy.
Time frame: Baseline, Week 26
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and n (Number Analyzed) signifies participants evaluable for specified rows. As pre-specified in the SAP, participant wise data was collected and reported due to very limited number of participants enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 26 in N-terminal-Pro-Hormone Brain Natriuretic Peptide (NT-proBNP) | Participant 1 | -202.376 nanograms/liter (ng/L) |
| Selexipag | Change From Baseline to Week 26 in N-terminal-Pro-Hormone Brain Natriuretic Peptide (NT-proBNP) | Participant 2 | 142.9233 nanograms/liter (ng/L) |
| Selexipag | Change From Baseline to Week 26 in N-terminal-Pro-Hormone Brain Natriuretic Peptide (NT-proBNP) | Participant 3 | -261.4904 nanograms/liter (ng/L) |
| Selexipag | Change From Baseline to Week 26 in N-terminal-Pro-Hormone Brain Natriuretic Peptide (NT-proBNP) | Participant 4 | 78.6501 nanograms/liter (ng/L) |
| Selexipag | Change From Baseline to Week 26 in N-terminal-Pro-Hormone Brain Natriuretic Peptide (NT-proBNP) | Participant 5 | -215.8226 nanograms/liter (ng/L) |
| Selexipag | Change From Baseline to Week 26 in N-terminal-Pro-Hormone Brain Natriuretic Peptide (NT-proBNP) | Participant 6 | -762.5677 nanograms/liter (ng/L) |
Secondary
Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 3 Variables
The risk score is derived for each participant considering the following non-invasive low-risk criteria among the 3 variables: WHO FC I-II, 6MWD \>440 m, NT-proBNP \< 300 ng/L. Number of low-risk criteria at baseline and Week 26 constitutes risk score and were derived for each participant by adding '1' for each of above criteria met. Number of low-risk criteria among the 3 variables for each participant can vary from 0 (worse participants) to 3 (healthier participants). Higher score indicated healthier participants.
Time frame: Baseline, Week 26
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and n (Number Analyzed) signifies participants evaluable for specified rows. As pre-specified in the SAP, participant wise data was collected and reported due to very limited number of participants enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 3 Variables | Participant 1 | 1 Score on a scale |
| Selexipag | Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 3 Variables | Participant 2 | 0 Score on a scale |
| Selexipag | Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 3 Variables | Participant 3 | 2 Score on a scale |
| Selexipag | Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 3 Variables | Participant 4 | 1 Score on a scale |
| Selexipag | Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 3 Variables | Participant 5 | 1 Score on a scale |
| Selexipag | Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 3 Variables | Participant 6 | 1 Score on a scale |
Secondary
Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 8 Variables
The risk score is derived for each participant considering the following non-invasive low-risk criteria among the 8 variables: absence of clinical signs of right heart failure, absence of symptoms progression, absence of syncope, WHO FC I-II, 6MWD greater than (\>) 440 meter, NT-proBNP less than (\<) 300 ng/L, Right atrial (RA) area \<18 centimeter square (cm\^2) as determined by echocardiography (Echo), absence of pericardial effusion, as determined by Echo. Number of low-risk criteria at baseline and Week 26 constitutes risk score and were derived for each participant by adding '1' for each of above criteria met. Number of low-risk criteria among the 8 variables for each participant can vary from 0 (worse participants) to 8 (healthier participants). Higher score indicated healthier participants.
Time frame: Baseline, Week 26
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and n (Number Analyzed) signifies participants evaluable for specified rows. As pre-specified in the SAP, participant wise data was collected and reported due to very limited number of participants enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 8 Variables | Participant 1 | 1 Score on a scale |
| Selexipag | Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 8 Variables | Participant 2 | 1 Score on a scale |
| Selexipag | Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 8 Variables | Participant 4 | 1 Score on a scale |
| Selexipag | Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 8 Variables | Participant 5 | 1 Score on a scale |
| Selexipag | Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 8 Variables | Participant 6 | 1 Score on a scale |
| Selexipag | Change From Baseline to Week 26 in Number of Non-invasive Low-risk Criteria Among the 8 Variables | Participant 3 | 3 Score on a scale |
Secondary
Change From Baseline to Week 26 in Right Ventricular Ejection Fraction (RVEF) Assessed by MRI
Change from baseline to Week 26 in RVEF assessed by MRI was reported. RVEF was the fraction of the end-diastolic volume (EDV) that is ejected out of right ventricle with each contraction. EDV is the volume of blood within a ventricle immediately before a contraction.
Time frame: Baseline, Week 26
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and n (Number Analyzed) signifies participants evaluable for specified rows. As pre-specified in the SAP, participant wise data was collected and reported due to very limited number of participants enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Ejection Fraction (RVEF) Assessed by MRI | Participant 3 | 6.96 Percentage of EDV |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Ejection Fraction (RVEF) Assessed by MRI | Participant 4 | 5.01 Percentage of EDV |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Ejection Fraction (RVEF) Assessed by MRI | Participant 5 | 19.12 Percentage of EDV |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Ejection Fraction (RVEF) Assessed by MRI | Participant 6 | 7.62 Percentage of EDV |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Ejection Fraction (RVEF) Assessed by MRI | Participant 1 | 9.65 Percentage of EDV |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Ejection Fraction (RVEF) Assessed by MRI | Participant 2 | 0.42 Percentage of EDV |
Secondary
Change From Baseline to Week 26 in Right Ventricular End-Diastolic Volume (RVEDV) Assessed by MRI
Change from baseline to Week 26 in RVEDV assessed by MRI was reported.
Time frame: Baseline, Week 26
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and n (Number Analyzed) signifies participants evaluable for specified rows. As pre-specified in the SAP, participant wise data was collected and reported due to very limited number of participants enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 26 in Right Ventricular End-Diastolic Volume (RVEDV) Assessed by MRI | Participant 5 | 3.71 Milliliter |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular End-Diastolic Volume (RVEDV) Assessed by MRI | Participant 6 | 7.82 Milliliter |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular End-Diastolic Volume (RVEDV) Assessed by MRI | Participant 1 | 40.57 Milliliter |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular End-Diastolic Volume (RVEDV) Assessed by MRI | Participant 2 | -8.89 Milliliter |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular End-Diastolic Volume (RVEDV) Assessed by MRI | Participant 3 | 23.58 Milliliter |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular End-Diastolic Volume (RVEDV) Assessed by MRI | Participant 4 | 6.79 Milliliter |
Secondary
Change From Baseline to Week 26 in Right Ventricular End-Systolic Volume (RVESV) Assessed by MRI
Change from baseline to Week 26 in RVESV assessed by MRI was reported.
Time frame: Baseline, Week 26
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and n (Number Analyzed) signifies participants evaluable for specified rows. As pre-specified in the SAP, participant wise data was collected and reported due to very limited number of participants enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 26 in Right Ventricular End-Systolic Volume (RVESV) Assessed by MRI | Participant 1 | 2.23 Milliliter |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular End-Systolic Volume (RVESV) Assessed by MRI | Participant 2 | -7.36 Milliliter |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular End-Systolic Volume (RVESV) Assessed by MRI | Participant 3 | 7.05 Milliliter |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular End-Systolic Volume (RVESV) Assessed by MRI | Participant 4 | -4.22 Milliliter |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular End-Systolic Volume (RVESV) Assessed by MRI | Participant 5 | -23.5 Milliliter |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular End-Systolic Volume (RVESV) Assessed by MRI | Participant 6 | -6.25 Milliliter |
Secondary
Change From Baseline to Week 26 in Right Ventricular Global Longitudinal Strain (RVGLS) Assessed by MRI
Change in RVGLS was a measure of longitudinal percent change in length of endocardium at Week 26 from baseline length assessed by MRI.
Time frame: Baseline, Week 26
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and n (Number Analyzed) signifies participants evaluable for specified rows. As pre-specified in the SAP, participant wise data was collected and reported due to very limited number of participants enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Global Longitudinal Strain (RVGLS) Assessed by MRI | Participant 4: RVGLS Endocardium | -5.61 Percent change in length of endocardium |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Global Longitudinal Strain (RVGLS) Assessed by MRI | Participant 1: RVGLS Endocardium | -4.26 Percent change in length of endocardium |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Global Longitudinal Strain (RVGLS) Assessed by MRI | Participant 2: RVGLS Endocardium | -5.31 Percent change in length of endocardium |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Global Longitudinal Strain (RVGLS) Assessed by MRI | Participant 3: RVGLS Endocardium | -12.8 Percent change in length of endocardium |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Global Longitudinal Strain (RVGLS) Assessed by MRI | Participant 5: RVGLS Endocardium | -14.45 Percent change in length of endocardium |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular Global Longitudinal Strain (RVGLS) Assessed by MRI | Participant 6: RVGLS Endocardium | -1.74 Percent change in length of endocardium |
Secondary
Change From Baseline to Week 26 in Right Ventricular (RV) Mass Index Assessed by MRI
Change from baseline to Week 26 in RV mass index assessed by MRI was reported.
Time frame: Baseline, Week 26
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure and n (Number Analyzed) signifies participants evaluable for specified rows. As pre-specified in the SAP, participant wise data was collected and reported due to very limited number of participants enrolled.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 26 in Right Ventricular (RV) Mass Index Assessed by MRI | Participant 1 | -11.03 Grams per meter square (g/m^2) |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular (RV) Mass Index Assessed by MRI | Participant 2 | 2.72 Grams per meter square (g/m^2) |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular (RV) Mass Index Assessed by MRI | Participant 3 | -12.69 Grams per meter square (g/m^2) |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular (RV) Mass Index Assessed by MRI | Participant 4 | 0.09 Grams per meter square (g/m^2) |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular (RV) Mass Index Assessed by MRI | Participant 5 | -16.56 Grams per meter square (g/m^2) |
| Selexipag | Change From Baseline to Week 26 in Right Ventricular (RV) Mass Index Assessed by MRI | Participant 6 | -2.41 Grams per meter square (g/m^2) |
Secondary
Number of Participants With Adverse Events (AEs) Leading to Premature Discontinuation of Study Drug
Number of participants with AEs leading to premature discontinuation of study drug were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time frame: Day 1 up to last dose of study drug (up to Week 52)
Population: Safety analysis set included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Participants With Adverse Events (AEs) Leading to Premature Discontinuation of Study Drug | 0 Participants |
Secondary
Number of Participants With Adverse Events of Special Interest (AESI)
Number of participants with AESI were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AESI were anaemia, bleeding events, gastrointestinal disturbances denoting intestinal intussusception (manifested as ileus or obstruction), hyperthyroidism, hypotension, light-dependent non-melanoma skin malignancies, major adverse cardiovascular events (MACE), medication errors, ophthalmological effects associated to retinal vascular system, pregnancy, pulmonary venoocclusive disease associated with pulmonary oedema, renal function impairment / acute renal failure.
Time frame: Day 1 up to 3 days after last dose of study drug (up to 52 weeks and 3 days that is 367 days)
Population: Safety analysis set included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Participants With Adverse Events of Special Interest (AESI) | 3 Participants |
Secondary
Number of Participants With Change From Baseline to Week 26 in World Health Organization (WHO) Functional Class
WHO functional classification for PAH ranged from Class I (no limitation in physical activity, ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope), Class II (slight limitation of physical activity, ordinary physical activity cause undue dyspnea or fatigue, chest pain or near syncope), Class III (marked limitation of physical activity, less than ordinary activity cause undue dyspnea or fatigue, chest pain or near syncope) and Class IV (cannot perform a physical activity without any symptoms, dyspnea and/or fatigue may even be present at rest). Change from baseline in WHO functional class was classified into Improved, No change and Worsened. Improvement =reduction in functional class; worsened =increase in functional class; and no change = no change in functional class.
Time frame: Baseline, Week 26
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Selexipag | Number of Participants With Change From Baseline to Week 26 in World Health Organization (WHO) Functional Class | Baseline: Class I | 0 Participants |
| Selexipag | Number of Participants With Change From Baseline to Week 26 in World Health Organization (WHO) Functional Class | Baseline: Class II | 4 Participants |
| Selexipag | Number of Participants With Change From Baseline to Week 26 in World Health Organization (WHO) Functional Class | Baseline: Class III | 4 Participants |
| Selexipag | Number of Participants With Change From Baseline to Week 26 in World Health Organization (WHO) Functional Class | Baseline: Class IV | 0 Participants |
| Selexipag | Number of Participants With Change From Baseline to Week 26 in World Health Organization (WHO) Functional Class | Week 26: Improved | 3 Participants |
| Selexipag | Number of Participants With Change From Baseline to Week 26 in World Health Organization (WHO) Functional Class | Week 26: Unchanged | 5 Participants |
| Selexipag | Number of Participants With Change From Baseline to Week 26 in World Health Organization (WHO) Functional Class | Week 26: Worsened | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product. Any AE occurring at or after the initial administration of study intervention up to 3 days after last dose of study intervention was considered as treatment-emergent.
Time frame: Day 1 up to 3 days after last dose of study drug (up to 52 weeks and 3 days that is 367 days)
Population: Safety analysis set included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Selexipag | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 9 Participants |
| Selexipag | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Marked Laboratory Abnormalities
Number of participants with treatment-emergent marked laboratory abnormalities in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, creatinine, sodium, potassium, hemoglobin, hematocrit; EVF; PCV (male), hematocrit; EVF; PCV (female), platelets (assuming no platelet cluster), leukocytes; white blood cells, Neutrophils (Abs), Eosinophils (Abs), lymphocytes (Abs) were reported. Abnormalities that occurred after study treatment start and up to 3 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Treatment-emergent marked laboratory abnormalities were determined at the investigator's discretion.
Time frame: Day 1 up to 3 days after last dose of study drug (up to 52 weeks and 3 days that is 367 days)
Population: Safety analysis set included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Selexipag | Number of Participants With Treatment-Emergent Marked Laboratory Abnormalities | 3 Participants |