Trial Outcomes & Findings for An Upcoming Clinical Study to Measure the Safety and Impact of a Drug Called Macitentan in Teenage and Adult Fontan Patients. (NCT NCT03775421)

NCT ID: NCT03775421

Last Updated: 2023-03-07

Results Overview

An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after end of treatment (EOT) (limits included) within the analysis set was considered to be treatment-emergent.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

112 participants

Primary outcome timeframe

Up to 133 weeks

Results posted on

2023-03-07

Participant Flow

1 participant was enrolled twice with 2 different participant IDs but only 111 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure
Macitentan 10 mg
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Overall Study
STARTED
111
Overall Study
COMPLETED
1
Overall Study
NOT COMPLETED
110

Reasons for withdrawal

Reasons for withdrawal
Measure
Macitentan 10 mg
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Overall Study
Lost to Follow-up
2
Overall Study
Withdrawal by Subject
10
Overall Study
Physician Decision
3
Overall Study
Death
1
Overall Study
Study Terminated by Sponsor
94

Baseline Characteristics

An Upcoming Clinical Study to Measure the Safety and Impact of a Drug Called Macitentan in Teenage and Adult Fontan Patients.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Macitentan 10 mg
n=111 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Age, Continuous
25.1 years
STANDARD_DEVIATION 7.04 • n=99 Participants
Sex: Female, Male
Female
34 Participants
n=99 Participants
Sex: Female, Male
Male
77 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
3 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
96 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
12 Participants
n=99 Participants
Race/Ethnicity, Customized
American Indian or Alaska Native
0 Participants
n=99 Participants
Race/Ethnicity, Customized
Asian
13 Participants
n=99 Participants
Race/Ethnicity, Customized
Black or African American
0 Participants
n=99 Participants
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
0 Participants
n=99 Participants
Race/Ethnicity, Customized
White
87 Participants
n=99 Participants
Race/Ethnicity, Customized
More than one race
0 Participants
n=99 Participants
Race/Ethnicity, Customized
Unknown or Not Reported
0 Participants
n=99 Participants
Race/Ethnicity, Customized
Other
11 Participants
n=99 Participants
Region of Enrollment
AUSTRALIA
10 Participants
n=99 Participants
Region of Enrollment
CANADA
4 Participants
n=99 Participants
Region of Enrollment
CHINA
5 Participants
n=99 Participants
Region of Enrollment
CZECH REPUBLIC
16 Participants
n=99 Participants
Region of Enrollment
DENMARK
17 Participants
n=99 Participants
Region of Enrollment
FRANCE
7 Participants
n=99 Participants
Region of Enrollment
NEW ZEALAND
2 Participants
n=99 Participants
Region of Enrollment
POLAND
23 Participants
n=99 Participants
Region of Enrollment
TAIWAN
6 Participants
n=99 Participants
Region of Enrollment
UNITED KINGDOM
3 Participants
n=99 Participants
Region of Enrollment
UNITED STATES
18 Participants
n=99 Participants

PRIMARY outcome

Timeframe: Up to 133 weeks

Population: The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).

An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after end of treatment (EOT) (limits included) within the analysis set was considered to be treatment-emergent.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=111 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
68 Participants

PRIMARY outcome

Timeframe: Up to 133 weeks

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg.

An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Any SAE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be TESAEs.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=111 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Number of Participants With Treatment-emergent Serious AEs (TESAEs)
18 Participants

PRIMARY outcome

Timeframe: Up to 133 weeks

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg.

An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=111 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Number of Participants With TEAEs Leading to Death
1 Participants

PRIMARY outcome

Timeframe: Up to 133 weeks

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg.

An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Any AE occurring at or after the study treatment start up to 30 days after EOT (limits included) within the analysis set was considered to be treatment-emergent.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=111 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Number of Participants With TEAEs Leading to Premature Discontinuation of Study Treatment
2 Participants

PRIMARY outcome

Timeframe: Up to 133 weeks

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "n" specifies those participants who were analyzed for each specific category.

Number of participants with treatment-emergent marked laboratory abnormalities (Hemoglobin \[gram/Liter {g/L}\], Platelets \[giga/L {10\^9 cells/L}\], Leukocytes \[10\^9 cells/L\], Lymphocytes \[10\^9 cells/L\], Neutrophils \[10\^9 cells/L\], Prothrombin International Normalized Ratio \[PINR;Ratio\], Aspartate Aminotransferase \[Units/L {U/L}\], Bilirubin \[micromoles/L {mcmol/L}\], Alkaline Phosphatase \[U/L\], Glomerular Filtration Rate \[milliliter/minute/1.73 meter square\], Glucose \[millimoles/L {mmol/L}\], Potassium \[mmol/L\], Sodium \[mmol/L\], Triglycerides \[mmol/L\] were reported. Abnormalities that occurred after study treatment start and up to 30 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Marked laboratory abnormalities reported for at least 1 participant were reported in this outcome measure. \>=:greater than or equal to; \>:greater than; \<:less than; ULN: upper limit of normal; L:Low, H:High, LLL:lower/worse than LL, HHH:higher/worse than HH.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=111 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Leukocytes: LLL (< 1.9)
2 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Leukocytes: LL (< 3.0)
10 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Lymphocytes: HH (> 4.0)
1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Neutrophils: LL (< 1.5)
3 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
PINR: HH (>=1.5 ULN)
4 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
PINR: HHH (>= 2.5 ULN)
1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Aspartate Aminotransferase: HH (>=3 ULN)
1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Bilirubin: HH (>=2 ULN)
1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Alkaline Phosphatase: HH (> 2.5 ULN)
1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
GFR: LL (< 60)
1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Glucose: LL (< 3.0)
2 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Glucose: HH (> 8.9)
3 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Potassium: HH (>5.5)
1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Sodium: LLL (<130)
1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Triglycerides: HH (>3.42)
3 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Hemoglobin: LL<100
1 Participants
Number of Participants With Treatment-emergent Marked Laboratory Abnormalities up to 30 Days After Study Treatment Discontinuation
Platelets: LL (< 75)
3 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 130

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (overall number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in hemoglobin over time was reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=98 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Hemoglobin Over Time
Week 26
-6.0 g/L
Standard Deviation 9.94
Change From Baseline in Hemoglobin Over Time
Week 52
-4.0 g/L
Standard Deviation 9.19
Change From Baseline in Hemoglobin Over Time
Week 78
-5.0 g/L
Standard Deviation 7.20
Change From Baseline in Hemoglobin Over Time
Week 104
-2.4 g/L
Standard Deviation 10.66
Change From Baseline in Hemoglobin Over Time
Week 130
5.7 g/L
Standard Deviation 19.35

PRIMARY outcome

Timeframe: Baseline up to Week 130

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in hematocrit over time was reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=100 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Hematocrit Over Time
Week 26
-0.016 Liters/Liter (L/L)
Standard Deviation 0.0323
Change From Baseline in Hematocrit Over Time
Week 52
-0.007 Liters/Liter (L/L)
Standard Deviation 0.0288
Change From Baseline in Hematocrit Over Time
Week 78
-0.011 Liters/Liter (L/L)
Standard Deviation 0.0247
Change From Baseline in Hematocrit Over Time
Week 104
-0.008 Liters/Liter (L/L)
Standard Deviation 0.0285
Change From Baseline in Hematocrit Over Time
Week 130
0.010 Liters/Liter (L/L)
Standard Deviation 0.0624

PRIMARY outcome

Timeframe: Baseline up to Week 130

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in leukocytes, neutrophils, lymphocytes, and platelets over time were reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=100 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Leukocytes: Week 26
-0.358 10^9 cells/L
Standard Deviation 1.2966
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Leukocytes: Week 52
-0.222 10^9 cells/L
Standard Deviation 1.3677
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Leukocytes: Week 78
-0.300 10^9 cells/L
Standard Deviation 1.2868
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Leukocytes: Week 104
-0.255 10^9 cells/L
Standard Deviation 1.2914
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Leukocytes: Week 130
-0.560 10^9 cells/L
Standard Deviation 1.1186
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Neutrophils: Week 26
-0.185 10^9 cells/L
Standard Deviation 1.0712
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Neutrophils: Week 52
-0.074 10^9 cells/L
Standard Deviation 1.0624
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Neutrophils: Week 78
-0.233 10^9 cells/L
Standard Deviation 1.0569
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Neutrophils: Week 104
-0.105 10^9 cells/L
Standard Deviation 1.1060
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Neutrophils: Week 130
-0.400 10^9 cells/L
Standard Deviation 1.0130
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Lymphocytes: Week 26
-0.153 10^9 cells/L
Standard Deviation 0.3176
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Lymphocytes: Week 52
-0.098 10^9 cells/L
Standard Deviation 0.5366
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Lymphocytes: Week 78
-0.016 10^9 cells/L
Standard Deviation 0.3046
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Lymphocytes: Week 104
-0.089 10^9 cells/L
Standard Deviation 0.3181
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Lymphocytes: Week 130
-0.113 10^9 cells/L
Standard Deviation 0.2223
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Platelets: Week 26
-9.2 10^9 cells/L
Standard Deviation 24.94
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Platelets: Week 52
-4.3 10^9 cells/L
Standard Deviation 30.54
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Platelets: Week 78
-8.1 10^9 cells/L
Standard Deviation 24.18
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Platelets: Week 104
-11.1 10^9 cells/L
Standard Deviation 25.08
Change From Baseline in Leukocytes, Neutrophils, Lymphocytes, and Platelets Over Time
Platelets: Week 130
6.7 10^9 cells/L
Standard Deviation 12.74

PRIMARY outcome

Timeframe: Baseline up to Week 130

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in systolic and diastolic arterial BP over time was reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=101 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
Systolic BP: Week 26
-0.7 millimeters of mercury (mmHg)
Standard Deviation 13.00
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
Systolic BP: Week 52
-1.7 millimeters of mercury (mmHg)
Standard Deviation 14.81
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
Systolic BP: Week 78
-0.7 millimeters of mercury (mmHg)
Standard Deviation 14.79
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
Systolic BP: Week 104
0.7 millimeters of mercury (mmHg)
Standard Deviation 6.49
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
Systolic BP: Week 130
-12 millimeters of mercury (mmHg)
Standard Deviation 8.72
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
Diastolic BP: Week 26
-2.9 millimeters of mercury (mmHg)
Standard Deviation 12.63
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
Diastolic BP: Week 52
-0.9 millimeters of mercury (mmHg)
Standard Deviation 12.56
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
Diastolic BP: Week 78
-1.6 millimeters of mercury (mmHg)
Standard Deviation 11.61
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
Diastolic BP: Week 104
2.6 millimeters of mercury (mmHg)
Standard Deviation 9.65
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP) Over Time
Diastolic BP: Week 130
-0.7 millimeters of mercury (mmHg)
Standard Deviation 7.23

PRIMARY outcome

Timeframe: Baseline up to Week 130

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in pulse rate over time was reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=101 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Pulse Rate Over Time
Week 26
-2.1 beats per minute (bpm)
Standard Deviation 10.48
Change From Baseline in Pulse Rate Over Time
Week 52
0.9 beats per minute (bpm)
Standard Deviation 10.95
Change From Baseline in Pulse Rate Over Time
Week 78
-1.3 beats per minute (bpm)
Standard Deviation 10.12
Change From Baseline in Pulse Rate Over Time
Week 104
-1.7 beats per minute (bpm)
Standard Deviation 8.78
Change From Baseline in Pulse Rate Over Time
Week 130
-0.3 beats per minute (bpm)
Standard Deviation 13.05

PRIMARY outcome

Timeframe: Baseline up to Week 130

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in SpO2 over time was reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=99 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time
Week 26
0.2 percentage of SpO2 (%)
Standard Deviation 3.22
Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time
Week 52
0.2 percentage of SpO2 (%)
Standard Deviation 2.79
Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time
Week 78
-0.5 percentage of SpO2 (%)
Standard Deviation 2.52
Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time
Week 104
0.3 percentage of SpO2 (%)
Standard Deviation 2.44
Change From Baseline in Peripheral Oxygen Saturation (SpO2) Over Time
Week 130
3.3 percentage of SpO2 (%)
Standard Deviation 2.31

PRIMARY outcome

Timeframe: Baseline up to Week 130

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in body weight over time was reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=102 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Body Weight Over Time
Week 26
0.8 kilograms (kg)
Standard Deviation 2.89
Change From Baseline in Body Weight Over Time
Week 52
0.9 kilograms (kg)
Standard Deviation 4.23
Change From Baseline in Body Weight Over Time
Week 78
1.7 kilograms (kg)
Standard Deviation 3.65
Change From Baseline in Body Weight Over Time
Week 104
2.0 kilograms (kg)
Standard Deviation 4.17
Change From Baseline in Body Weight Over Time
Week 130
2.6 kilograms (kg)
Standard Deviation 5.54

PRIMARY outcome

Timeframe: Baseline up to Week 130

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in ALT, AST, AP, and GGT over time were reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=103 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
ALT: Week 26
-2.0 U/L
Standard Deviation 8.57
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
ALT: Week 52
-2.1 U/L
Standard Deviation 10.40
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
ALT: Week 78
-2.7 U/L
Standard Deviation 11.32
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
ALT: Week 104
-6.8 U/L
Standard Deviation 15.72
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
ALT: Week 130
-13.7 U/L
Standard Deviation 23.69
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
AST: Week 26
-1.3 U/L
Standard Deviation 8.39
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
AST: Week 52
-1.7 U/L
Standard Deviation 9.60
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
AST: Week 78
-3.0 U/L
Standard Deviation 11.39
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
AST: Week 104
-6.1 U/L
Standard Deviation 17.03
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
AST: Week 130
-21.3 U/L
Standard Deviation 41.43
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
AP: Week 26
-7.7 U/L
Standard Deviation 36.04
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
AP: Week 52
-1.9 U/L
Standard Deviation 25.25
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
AP: Week 78
-6.6 U/L
Standard Deviation 28.02
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
AP: Week 104
-21.8 U/L
Standard Deviation 53.46
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
AP: Week 130
6.7 U/L
Standard Deviation 6.03
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
GGT: Week 26
-1.2 U/L
Standard Deviation 14.85
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
GGT: Week 52
1.2 U/L
Standard Deviation 15.74
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
GGT: Week 78
-2.2 U/L
Standard Deviation 18.26
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
GGT: Week 104
-3.2 U/L
Standard Deviation 18.13
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl Transferase (GGT) Over Time
GGT: Week 130
1.0 U/L
Standard Deviation 13.23

PRIMARY outcome

Timeframe: Baseline up to Week 130

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in bilirubin, direct bilirubin, and creatinine over time were reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=103 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Bilirubin: Week 26
-0.9 micromoles per liter (mcmol/L)
Standard Deviation 6.62
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Bilirubin: Week 52
-1.1 micromoles per liter (mcmol/L)
Standard Deviation 10.41
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Bilirubin: Week 78
-0.5 micromoles per liter (mcmol/L)
Standard Deviation 5.68
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Bilirubin: Week 104
-0.8 micromoles per liter (mcmol/L)
Standard Deviation 6.13
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Bilirubin: Week 130
-1.3 micromoles per liter (mcmol/L)
Standard Deviation 2.89
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Direct Bilirubin: Week 26
-0.1 micromoles per liter (mcmol/L)
Standard Deviation 1.14
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Direct Bilirubin: Week 52
0.0 micromoles per liter (mcmol/L)
Standard Deviation 1.29
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Direct Bilirubin: Week 78
0.0 micromoles per liter (mcmol/L)
Standard Deviation 1.00
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Direct Bilirubin: Week 104
-0.2 micromoles per liter (mcmol/L)
Standard Deviation 1.25
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Direct Bilirubin: Week 130
-1.0 micromoles per liter (mcmol/L)
Standard Deviation 1.00
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Creatinine: Week 26
0.2 micromoles per liter (mcmol/L)
Standard Deviation 9.27
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Creatinine: Week 52
0.9 micromoles per liter (mcmol/L)
Standard Deviation 9.16
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Creatinine: Week 78
0.8 micromoles per liter (mcmol/L)
Standard Deviation 8.22
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Creatinine: Week 104
0.1 micromoles per liter (mcmol/L)
Standard Deviation 8.10
Change From Baseline in Bilirubin, Direct Bilirubin, and Creatinine Over Time
Creatinine: Week 130
-0.7 micromoles per liter (mcmol/L)
Standard Deviation 5.51

PRIMARY outcome

Timeframe: Baseline up to Week 130

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in GFR over time was reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=102 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Glomerular Filtration Rate (GFR) Over Time
Week 26
-0.9 milliliters/minute/1.73 meter square
Standard Deviation 15.43
Change From Baseline in Glomerular Filtration Rate (GFR) Over Time
Week 52
-2.0 milliliters/minute/1.73 meter square
Standard Deviation 15.22
Change From Baseline in Glomerular Filtration Rate (GFR) Over Time
Week 78
-0.5 milliliters/minute/1.73 meter square
Standard Deviation 13.26
Change From Baseline in Glomerular Filtration Rate (GFR) Over Time
Week 104
0.4 milliliters/minute/1.73 meter square
Standard Deviation 17.00
Change From Baseline in Glomerular Filtration Rate (GFR) Over Time
Week 130
-1.7 milliliters/minute/1.73 meter square
Standard Deviation 7.57

PRIMARY outcome

Timeframe: Baseline up to Week 130

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in prothrombin time over time was reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=98 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Prothrombin Time Over Time
Week 26
-0.31 seconds
Standard Deviation 3.523
Change From Baseline in Prothrombin Time Over Time
Week 52
-0.05 seconds
Standard Deviation 4.038
Change From Baseline in Prothrombin Time Over Time
Week 78
-0.38 seconds
Standard Deviation 2.293
Change From Baseline in Prothrombin Time Over Time
Week 104
-1.12 seconds
Standard Deviation 3.317
Change From Baseline in Prothrombin Time Over Time
Week 130
-0.57 seconds
Standard Deviation 0.651

PRIMARY outcome

Timeframe: Baseline up to Week 130

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in prothrombin international normalized ratio over time was reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=98 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Prothrombin International Normalized Ratio Over Time
Week 26
-0.06 ratio
Standard Deviation 0.401
Change From Baseline in Prothrombin International Normalized Ratio Over Time
Week 52
-0.06 ratio
Standard Deviation 0.456
Change From Baseline in Prothrombin International Normalized Ratio Over Time
Week 78
-0.12 ratio
Standard Deviation 0.245
Change From Baseline in Prothrombin International Normalized Ratio Over Time
Week 104
-0.16 ratio
Standard Deviation 0.379
Change From Baseline in Prothrombin International Normalized Ratio Over Time
Week 130
-0.07 ratio
Standard Deviation 0.058

SECONDARY outcome

Timeframe: Baseline, Week 52, and Week 104

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in peak VO2 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=71 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Peak Oxygen Uptake/Consumption (VO2)
Week 52
-0.82 Milliliters per kilogram per minute
Standard Deviation 2.724
Change From Baseline in Peak Oxygen Uptake/Consumption (VO2)
Week 104
-0.93 Milliliters per kilogram per minute
Standard Deviation 1.968

SECONDARY outcome

Timeframe: Baseline, Week 26, Week 52, Week 78, and Week 104

Population: The RUBATO OLES included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 mg. Here, "N" (number of participants analyzed) specifies number of participants evaluable for this outcome measure and; "n" specifies those participants who were analyzed at specified timepoints.

Change from baseline in mean count per minute of daily PA-Ac was reported in this outcome measure.

Outcome measures

Outcome measures
Measure
Macitentan 10 mg
n=42 Participants
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)
Week 26
19.74 mean count per minute
Standard Deviation 131.622
Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)
Week 52
44.58 mean count per minute
Standard Deviation 153.196
Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)
Week 78
99.14 mean count per minute
Standard Deviation 165.965
Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac)
Week 104
-62.87 mean count per minute
Standard Deviation 189.264

Adverse Events

Macitentan 10 mg

Serious events: 18 serious events
Other events: 34 other events
Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure
Macitentan 10 mg
n=111 participants at risk
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Cardiac disorders
Arrhythmia
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Cardiac disorders
Atrial Flutter
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Gastrointestinal disorders
Abdominal Pain
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Gastrointestinal disorders
Colitis Ulcerative
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Gastrointestinal disorders
Incarcerated Inguinal Hernia
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
General disorders
Death
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Hepatobiliary disorders
Hepatic Mass
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations
Covid-19
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations
Cytomegalovirus Infection
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations
Pneumonia
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Injury, poisoning and procedural complications
Anastomotic Stenosis
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Investigations
Sperm Concentration Decreased
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Investigations
Spermatozoa Progressive Motility Decreased
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular Carcinoma
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Nervous system disorders
Cerebrovascular Accident
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Nervous system disorders
Clonic Convulsion
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Nervous system disorders
Epilepsy
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Psychiatric disorders
Anxiety
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Psychiatric disorders
Depression
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Psychiatric disorders
Mental Disorder
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Psychiatric disorders
Suicidal Ideation
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Respiratory, thoracic and mediastinal disorders
Hypoxia
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Respiratory, thoracic and mediastinal disorders
Pleurisy
0.90%
1/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).

Other adverse events

Other adverse events
Measure
Macitentan 10 mg
n=111 participants at risk
Participants received macitentan 10 milligrams (mg) tablet orally once daily with or without food from Day 1 until the end of the treatment (129 weeks) or till the sponsor decided to stop this study.
Cardiac disorders
Palpitations
6.3%
7/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
General disorders
Fatigue
6.3%
7/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
General disorders
Pyrexia
2.7%
3/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations
Covid-19
11.7%
13/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations
Pharyngitis
2.7%
3/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Infections and infestations
Tonsillitis
2.7%
3/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Nervous system disorders
Dizziness
2.7%
3/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Nervous system disorders
Headache
7.2%
8/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Psychiatric disorders
Anxiety
4.5%
5/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Respiratory, thoracic and mediastinal disorders
Cough
3.6%
4/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).
Respiratory, thoracic and mediastinal disorders
Dyspnoea
4.5%
5/111 • Up to 133 weeks
The RUBATO open-label extension set (OLES) included all participants who were enrolled in this study and received at least 1 dose of macitentan 10 milligrams (mg).

Additional Information

Senior Clinical Leader PH

Actelion Pharmaceuticals Ltd

Phone: 844-434-4210

Results disclosure agreements

  • Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 30 days before submission for publication or presentation.
  • Publication restrictions are in place

Restriction type: OTHER