Trial Outcomes & Findings for Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects (NCT NCT03153137)
NCT ID: NCT03153137
Last Updated: 2025-03-30
Results Overview
Change from baseline in peak VO2 up to Week 16 was reported.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
142 participants
Primary outcome timeframe
Baseline up to Week 16
Results posted on
2025-03-30
Participant Flow
A total of 142 participants were enrolled, out of which 137 participants were included in the analysis as 5 participants were excluded due to regulatory restrictions.
Participant milestones
| Measure |
Placebo
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Overall Study
STARTED
|
69
|
68
|
|
Overall Study
COMPLETED
|
66
|
64
|
|
Overall Study
NOT COMPLETED
|
3
|
4
|
Reasons for withdrawal
| Measure |
Placebo
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
|
Overall Study
Physician Decision
|
0
|
3
|
Baseline Characteristics
Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
Baseline characteristics by cohort
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
Total
n=137 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
24.5 years
STANDARD_DEVIATION 7.49 • n=99 Participants
|
23.2 years
STANDARD_DEVIATION 5.82 • n=107 Participants
|
23.9 years
STANDARD_DEVIATION 6.72 • n=206 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
48 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
44 Participants
n=99 Participants
|
45 Participants
n=107 Participants
|
89 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
59 Participants
n=99 Participants
|
58 Participants
n=107 Participants
|
117 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
8 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
10 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
52 Participants
n=99 Participants
|
55 Participants
n=107 Participants
|
107 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Region of Enrollment
Australia
|
7 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Region of Enrollment
Canada
|
1 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Region of Enrollment
China
|
3 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Region of Enrollment
Czech Republic
|
9 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Region of Enrollment
Denmark
|
10 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Region of Enrollment
France
|
5 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Region of Enrollment
New Zealand
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Region of Enrollment
Poland
|
17 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Region of Enrollment
Taiwan, Province Of China
|
4 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Region of Enrollment
United Kingdom
|
1 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
11 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 16Population: Full analysis set (FAS) included all participants randomized to the study treatment.
Change from baseline in peak VO2 up to Week 16 was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Peak Oxygen Uptake/Consumption (VO2) Up to Week 16
|
-0.67 Milliliter/kilogram/minute (mL/kg/min)
Standard Deviation 2.657 • Interval 2.657 to
|
-0.16 Milliliter/kilogram/minute (mL/kg/min)
Standard Deviation 2.855 • Interval 2.855 to
|
SECONDARY outcome
Timeframe: Baseline up to Week 52Population: FAS included all participants randomized to the study treatment.
Change from baseline in peak VO2 up to Week 52 was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Peak VO2 Up to Week 52
|
-0.92 mL/kg/min
Standard Error 0.296 • Interval 0.296 to
|
-0.31 mL/kg/min
Standard Error 0.293 • Interval 0.293 to
|
SECONDARY outcome
Timeframe: Baseline up to Week 16Population: FAS included all participants randomized to the study treatment. Here, N (number of participants analyzed) is defined as the number of participants evaluable for this outcome measure.
Change from baseline in mean count per minute of daily PA-Ac up to Week 16 was reported. The daily physical activity (counts per min) of the participant was assessed via accelerometer during daytime. The accelerometer was given to the participant at Visit 1, and data was collected for 9 consecutive daily daytime periods after Visit 1 (baseline) to Visit 4 (Week 16).
Outcome measures
| Measure |
Placebo
n=58 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=61 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Mean Count Per Minute of Daily Physical Activity Measured by Accelerometer (PA-Ac) Up to Week 16
|
-14.34 counts per minute
Standard Deviation 117.562
|
-3.02 counts per minute
Standard Deviation 92.443
|
SECONDARY outcome
Timeframe: Up to 56 weeksPopulation: The Safety analysis set included all participants who received at least one dose of study treatment.
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.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
|
9 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: Up to 56 weeksPopulation: The Safety analysis set included all participants who received at least one dose of study treatment.
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.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (AEs)
|
44 Participants
|
48 Participants
|
SECONDARY outcome
Timeframe: Up to 56 weeksPopulation: Safety set included all participants who received at least one dose of study treatment.
Number of participants with AEs leading to premature discontinuation of study treatment was reported. AEs leading to premature discontinuation of study treatment were those with action taken with study drug reported as 'permanently discontinued' by the investigator.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Number of Participants With AEs Leading to Premature Discontinuation of Study Treatment
|
1 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in systolic and diastolic arterial BP at Week 8, Week 16, Week 32 and Week 52 was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)
Baseline
|
116.0 millimeters of mercury (mmHg)
Standard Deviation 12.10
|
117.0 millimeters of mercury (mmHg)
Standard Deviation 10.95
|
|
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)
Systolic BP: Week 8
|
2.5 millimeters of mercury (mmHg)
Standard Deviation 14.41
|
-0.4 millimeters of mercury (mmHg)
Standard Deviation 11.67
|
|
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)
Systolic BP: Week 16
|
0.5 millimeters of mercury (mmHg)
Standard Deviation 14.68
|
-4.6 millimeters of mercury (mmHg)
Standard Deviation 13.05
|
|
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)
Systolic BP: Week 32
|
-6.3 millimeters of mercury (mmHg)
Standard Deviation 15.09
|
-3.1 millimeters of mercury (mmHg)
Standard Deviation 10.51
|
|
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)
Systolic BP: Week 52
|
0.0 millimeters of mercury (mmHg)
Standard Deviation 12.12
|
-4.8 millimeters of mercury (mmHg)
Standard Deviation 12.08
|
|
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)
Diastolic BP: Week 8
|
-0.2 millimeters of mercury (mmHg)
Standard Deviation 5.86
|
-0.1 millimeters of mercury (mmHg)
Standard Deviation 9.57
|
|
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)
Diastolic BP: Week 16
|
-0.6 millimeters of mercury (mmHg)
Standard Deviation 10.06
|
-3.1 millimeters of mercury (mmHg)
Standard Deviation 8.74
|
|
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)
Diastolic BP: Week 32
|
1.3 millimeters of mercury (mmHg)
Standard Deviation 8.64
|
-1.4 millimeters of mercury (mmHg)
Standard Deviation 8.21
|
|
Change From Baseline in Systolic and Diastolic Arterial Blood Pressure (BP)
Diastolic BP: Week 52
|
1.3 millimeters of mercury (mmHg)
Standard Deviation 10.84
|
-2.8 millimeters of mercury (mmHg)
Standard Deviation 11.21
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in pulse rate at Week 8, Week 16, Week 32 and Week 52 was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Pulse Rate
Baseline
|
81.3 beats per minute (bpm)
Standard Deviation 12.52
|
78.2 beats per minute (bpm)
Standard Deviation 13.33
|
|
Change From Baseline in Pulse Rate
Week 8
|
-3.9 beats per minute (bpm)
Standard Deviation 12.80
|
-5.9 beats per minute (bpm)
Standard Deviation 12.07
|
|
Change From Baseline in Pulse Rate
Week 16
|
0.1 beats per minute (bpm)
Standard Deviation 14.76
|
-0.1 beats per minute (bpm)
Standard Deviation 11.57
|
|
Change From Baseline in Pulse Rate
Week 32
|
0.2 beats per minute (bpm)
Standard Deviation 12.37
|
1.1 beats per minute (bpm)
Standard Deviation 9.10
|
|
Change From Baseline in Pulse Rate
Week 52
|
-0.7 beats per minute (bpm)
Standard Deviation 11.56
|
-2.9 beats per minute (bpm)
Standard Deviation 10.25
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in SpO2 was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Oxygen Saturation (SpO2)
Baseline
|
92.6 percent of oxygen saturation
Standard Deviation 3.22
|
92.8 percent of oxygen saturation
Standard Deviation 2.84
|
|
Change From Baseline in Oxygen Saturation (SpO2)
Week 8
|
0.0 percent of oxygen saturation
Standard Deviation 3.20
|
1.2 percent of oxygen saturation
Standard Deviation 2.78
|
|
Change From Baseline in Oxygen Saturation (SpO2)
Week 16
|
0.5 percent of oxygen saturation
Standard Deviation 2.57
|
0.8 percent of oxygen saturation
Standard Deviation 2.75
|
|
Change From Baseline in Oxygen Saturation (SpO2)
Week 32
|
0.8 percent of oxygen saturation
Standard Deviation 2.94
|
1.4 percent of oxygen saturation
Standard Deviation 3.73
|
|
Change From Baseline in Oxygen Saturation (SpO2)
Week 52
|
1.4 percent of oxygen saturation
Standard Deviation 2.77
|
0.9 percent of oxygen saturation
Standard Deviation 2.99
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in body weight was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Body Weight
Baseline
|
68.89 kilograms (kg)
Standard Deviation 17.296
|
67.38 kilograms (kg)
Standard Deviation 14.721
|
|
Change From Baseline in Body Weight
Week 8
|
-0.38 kilograms (kg)
Standard Deviation 1.996
|
0.43 kilograms (kg)
Standard Deviation 1.568
|
|
Change From Baseline in Body Weight
Week 16
|
0.21 kilograms (kg)
Standard Deviation 2.028
|
0.58 kilograms (kg)
Standard Deviation 2.230
|
|
Change From Baseline in Body Weight
Week 32
|
0.73 kilograms (kg)
Standard Deviation 2.952
|
0.77 kilograms (kg)
Standard Deviation 3.411
|
|
Change From Baseline in Body Weight
Week 52
|
1.44 kilograms (kg)
Standard Deviation 3.746
|
1.30 kilograms (kg)
Standard Deviation 4.358
|
SECONDARY outcome
Timeframe: Up to 56 weeksPopulation: Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure.
Number of participants with treatment-emergent markedly laboratory abnormal laboratory values were reported. Abnormal values for platelets (LL \< 75); Lymphocytes (HH \> 4.0); Neutrophils (LL \< 1.5); Prothrombin International Normalized Ratio: HH (greater than and equal to \[\>=\] 1.5 upper limit of normal \[ULN\]), Ratio: HH \>= 2.5 ULN); Bilirubin (HH \>= 2 ULN); Alkaline Phosphatase (HH \> 2.5 ULN); Glomerular Filtration Rate (LL \< 60); Glucose (HH \> 8.9); Triglycerides (HH \> 3.42). Here "HH" refers to values above the normal range, where H stands for "high" and "LL" refers to values below the normal range where L stands for "low".
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=67 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Platelets: LL (< 75)
|
2 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Lymphocytes: HH (> 4.0)
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Neutrophils: LL (< 1.5)
|
0 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Prothrombin International Normalized Ratio: HH (>= 1.5 ULN)
|
3 Participants
|
5 Participants
|
|
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Prothrombin International Normalized Ratio: HH (>= 2.5 ULN)
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Bilirubin: HH (>= 2 ULN)
|
1 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Alkaline Phosphatase: HH (> 2.5 ULN)
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Glomerular Filtration Rate: LL (< 60)
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Glucose: LL (< 3.0)
|
0 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Glucose: HH (> 8.9)
|
0 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Markedly Abnormal Laboratory Values
Triglycerides: HH (> 3.42)
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in hemoglobin was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=67 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Hemoglobin
Week 8
|
0.0 grams per liter (g/L)
Standard Deviation 6.59
|
-8.7 grams per liter (g/L)
Standard Deviation 9.33
|
|
Change From Baseline in Hemoglobin
Week 16
|
0.0 grams per liter (g/L)
Standard Deviation 7.75
|
-8.7 grams per liter (g/L)
Standard Deviation 8.51
|
|
Change From Baseline in Hemoglobin
Week 32
|
1.3 grams per liter (g/L)
Standard Deviation 8.29
|
-7.3 grams per liter (g/L)
Standard Deviation 9.84
|
|
Change From Baseline in Hemoglobin
Week 52
|
-2.9 grams per liter (g/L)
Standard Deviation 10.04
|
-7.1 grams per liter (g/L)
Standard Deviation 10.02
|
|
Change From Baseline in Hemoglobin
Baseline
|
160.4 grams per liter (g/L)
Standard Deviation 13.43
|
159.5 grams per liter (g/L)
Standard Deviation 12.83
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in hematocrit was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=67 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Hematocrit
Baseline
|
0.472 Liter/Liter (L/L)
Standard Deviation 0.041
|
0.471 Liter/Liter (L/L)
Standard Deviation 0.034
|
|
Change From Baseline in Hematocrit
Week 8
|
0.002 Liter/Liter (L/L)
Standard Deviation 0.027
|
-0.030 Liter/Liter (L/L)
Standard Deviation 0.023
|
|
Change From Baseline in Hematocrit
Week 16
|
0.003 Liter/Liter (L/L)
Standard Deviation 0.027
|
-0.023 Liter/Liter (L/L)
Standard Deviation 0.026
|
|
Change From Baseline in Hematocrit
Week 32
|
0.003 Liter/Liter (L/L)
Standard Deviation 0.031
|
-0.009 Liter/Liter (L/L)
Standard Deviation 0.028
|
|
Change From Baseline in Hematocrit
Week 52
|
-0.010 Liter/Liter (L/L)
Standard Deviation 0.030
|
-0.021 Liter/Liter (L/L)
Standard Deviation 0.028
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in erythrocytes and reticulocytes at Week 8, Week 16, Week 32 and Week 52 was reported.
Outcome measures
| Measure |
Placebo
n=68 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=64 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Erythrocytes and Reticulocytes
Reticulocytes: Week 32
|
-0.003 10^12 cells per liter
Standard Deviation 0.028
|
-0.008 10^12 cells per liter
Standard Deviation 0.027
|
|
Change From Baseline in Erythrocytes and Reticulocytes
Erythrocytes: Baseline
|
5.251 10^12 cells per liter
Standard Deviation 0.4832
|
5.205 10^12 cells per liter
Standard Deviation 0.3544
|
|
Change From Baseline in Erythrocytes and Reticulocytes
Erythrocytes: Week 8
|
0.048 10^12 cells per liter
Standard Deviation 0.2461
|
-0.297 10^12 cells per liter
Standard Deviation 0.2866
|
|
Change From Baseline in Erythrocytes and Reticulocytes
Erythrocytes: Week 16
|
0.012 10^12 cells per liter
Standard Deviation 0.2521
|
-0.264 10^12 cells per liter
Standard Deviation 0.2790
|
|
Change From Baseline in Erythrocytes and Reticulocytes
Erythrocytes: Week 32
|
-0.031 10^12 cells per liter
Standard Deviation 0.2442
|
-0.090 10^12 cells per liter
Standard Deviation 0.2337
|
|
Change From Baseline in Erythrocytes and Reticulocytes
Erythrocytes: Week 52
|
-0.096 10^12 cells per liter
Standard Deviation 0.2515
|
-0.184 10^12 cells per liter
Standard Deviation 0.2671
|
|
Change From Baseline in Erythrocytes and Reticulocytes
Reticulocytes: Baseline:
|
0.075 10^12 cells per liter
Standard Deviation 0.028
|
0.070 10^12 cells per liter
Standard Deviation 0.022
|
|
Change From Baseline in Erythrocytes and Reticulocytes
Reticulocytes: Week 8
|
-0.006 10^12 cells per liter
Standard Deviation 0.017
|
-0.006 10^12 cells per liter
Standard Deviation 0.016
|
|
Change From Baseline in Erythrocytes and Reticulocytes
Reticulocytes: Week 16
|
-0.003 10^12 cells per liter
Standard Deviation 0.026
|
-0.001 10^12 cells per liter
Standard Deviation 0.021
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in leucocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets at Week 8, Week 16, Week 32 and Week 52 was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=67 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Leukocytes: Baseline
|
6.270 10^9 cells per liter
Standard Deviation 1.7553
|
5.693 10^9 cells per liter
Standard Deviation 1.5679
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Leukocytes: Week 8
|
-0.242 10^9 cells per liter
Standard Deviation 1.7651
|
-1.001 10^9 cells per liter
Standard Deviation 1.2096
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Leukocytes: Week 16
|
-0.199 10^9 cells per liter
Standard Deviation 1.5490
|
-0.378 10^9 cells per liter
Standard Deviation 1.3908
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Leukocytes: Week 32
|
0.417 10^9 cells per liter
Standard Deviation 1.1782
|
-0.237 10^9 cells per liter
Standard Deviation 1.7224
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Leukocytes: Week 52
|
-0.554 10^9 cells per liter
Standard Deviation 1.4050
|
-0.715 10^9 cells per liter
Standard Deviation 1.6433
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Neutrophils: Baseline
|
4.100 10^9 cells per liter
Standard Deviation 1.3222
|
3.831 10^9 cells per liter
Standard Deviation 1.1268
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Neutrophils: Week 8
|
-0.133 10^9 cells per liter
Standard Deviation 1.3604
|
-0.743 10^9 cells per liter
Standard Deviation 0.9864
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Neutrophils: Week 16
|
-0.291 10^9 cells per liter
Standard Deviation 1.3547
|
-0.373 10^9 cells per liter
Standard Deviation 1.0896
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Neutrophils: Week 32
|
0.494 10^9 cells per liter
Standard Deviation 0.9719
|
-0.254 10^9 cells per liter
Standard Deviation 1.2012
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Neutrophils: Week 52
|
-0.384 10^9 cells per liter
Standard Deviation 1.1619
|
-0.627 10^9 cells per liter
Standard Deviation 1.2475
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Lymphocytes: Baseline
|
1.489 10^9 cells per liter
Standard Deviation 0.6791
|
1.263 10^9 cells per liter
Standard Deviation 0.4974
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Lymphocytes: Week 8
|
-0.113 10^9 cells per liter
Standard Deviation 0.4770
|
-0.165 10^9 cells per liter
Standard Deviation 0.2886
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Lymphocytes: Week 16
|
0.073 10^9 cells per liter
Standard Deviation 0.4756
|
0.042 10^9 cells per liter
Standard Deviation 0.6164
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Lymphocytes: Week 32
|
0.047 10^9 cells per liter
Standard Deviation 0.3341
|
0.126 10^9 cells per liter
Standard Deviation 0.2269
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Lymphocytes: Week 52
|
-0.082 10^9 cells per liter
Standard Deviation 0.4740
|
-0.033 10^9 cells per liter
Standard Deviation 0.3890
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Baseline: Monocytes
|
0.416 10^9 cells per liter
Standard Deviation 0.1698
|
0.409 10^9 cells per liter
Standard Deviation 0.1541
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Monocytes: Week 8
|
-0.017 10^9 cells per liter
Standard Deviation 0.1645
|
-0.081 10^9 cells per liter
Standard Deviation 0.1400
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Monocytes: Week 16
|
0.002 10^9 cells per liter
Standard Deviation 0.1703
|
-0.050 10^9 cells per liter
Standard Deviation 0.1202
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Monocytes: Week 32
|
-0.018 10^9 cells per liter
Standard Deviation 0.1209
|
-0.071 10^9 cells per liter
Standard Deviation 0.1162
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Monocytes: Week 52
|
-0.039 10^9 cells per liter
Standard Deviation 0.1380
|
-0.077 10^9 cells per liter
Standard Deviation 0.1257
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Eosinophils: Baseline
|
0.207 10^9 cells per liter
Standard Deviation 0.3480
|
0.151 10^9 cells per liter
Standard Deviation 0.1333
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Eosinophils: Week 8
|
-0.003 10^9 cells per liter
Standard Deviation 0.5146
|
0.014 10^9 cells per liter
Standard Deviation 0.0816
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Eosinophils: Week 16
|
0.016 10^9 cells per liter
Standard Deviation 0.3056
|
0.002 10^9 cells per liter
Standard Deviation 0.0755
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Eosinophils: Week 32
|
-0.100 10^9 cells per liter
Standard Deviation 0.5447
|
0.029 10^9 cells per liter
Standard Deviation 0.1951
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Eosinophils: Week 52
|
-0.046 10^9 cells per liter
Standard Deviation 0.3597
|
0.015 10^9 cells per liter
Standard Deviation 0.1935
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Basophils: Baseline
|
0.055 10^9 cells per liter
Standard Deviation 0.0322
|
0.040 10^9 cells per liter
Standard Deviation 0.0245
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Basophils: Week 8
|
-0.002 10^9 cells per liter
Standard Deviation 0.0255
|
-0.002 10^9 cells per liter
Standard Deviation 0.0233
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Basophils: Week 16
|
0.004 10^9 cells per liter
Standard Deviation 0.0394
|
0.000 10^9 cells per liter
Standard Deviation 0.0363
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Basophils: Week 32
|
-0.003 10^9 cells per liter
Standard Deviation 0.0354
|
0.016 10^9 cells per liter
Standard Deviation 0.0313
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Basophils: Week 52
|
-0.003 10^9 cells per liter
Standard Deviation 0.0389
|
0.006 10^9 cells per liter
Standard Deviation 0.0281
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Platelets: Baseline
|
184.3 10^9 cells per liter
Standard Deviation 63.22
|
178.1 10^9 cells per liter
Standard Deviation 54.93
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Platelets: Week 8
|
-5.9 10^9 cells per liter
Standard Deviation 32.85
|
-9.1 10^9 cells per liter
Standard Deviation 35.38
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Platelets: Week 16
|
-5.4 10^9 cells per liter
Standard Deviation 30.33
|
-3.0 10^9 cells per liter
Standard Deviation 28.77
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Platelets: Week 32
|
-7.8 10^9 cells per liter
Standard Deviation 33.46
|
8.2 10^9 cells per liter
Standard Deviation 33.76
|
|
Change From Baseline in Leucocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils and Platelets
Platelets: Week 52
|
-11.2 10^9 cells per liter
Standard Deviation 29.94
|
-5.7 10^9 cells per liter
Standard Deviation 31.75
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in prothrombin time was reported.
Outcome measures
| Measure |
Placebo
n=67 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Prothrombin Time
Week 8
|
-0.23 Seconds (sec)
Standard Deviation 3.265
|
-0.53 Seconds (sec)
Standard Deviation 4.567
|
|
Change From Baseline in Prothrombin Time
Baseline
|
14.72 Seconds (sec)
Standard Deviation 7.033
|
15.37 Seconds (sec)
Standard Deviation 7.610
|
|
Change From Baseline in Prothrombin Time
Week 16
|
0.04 Seconds (sec)
Standard Deviation 3.921
|
0.36 Seconds (sec)
Standard Deviation 10.868
|
|
Change From Baseline in Prothrombin Time
Week 32
|
1.45 Seconds (sec)
Standard Deviation 8.261
|
0.03 Seconds (sec)
Standard Deviation 4.135
|
|
Change From Baseline in Prothrombin Time
Week 52
|
-0.64 Seconds (sec)
Standard Deviation 3.167
|
-1.20 Seconds (sec)
Standard Deviation 3.567
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in prothrombin international normalized ratio was reported.
Outcome measures
| Measure |
Placebo
n=67 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Prothrombin International Normalized Ratio
Baseline
|
1.434 Ratio
Standard Deviation 0.7364
|
1.516 Ratio
Standard Deviation 0.8014
|
|
Change From Baseline in Prothrombin International Normalized Ratio
Week 8
|
-0.009 Ratio
Standard Deviation 0.3216
|
-0.054 Ratio
Standard Deviation 0.4652
|
|
Change From Baseline in Prothrombin International Normalized Ratio
Week 16
|
0.015 Ratio
Standard Deviation 0.3806
|
0.049 Ratio
Standard Deviation 1.1653
|
|
Change From Baseline in Prothrombin International Normalized Ratio
Week 32
|
0.171 Ratio
Standard Deviation 0.9204
|
0.033 Ratio
Standard Deviation 0.4597
|
|
Change From Baseline in Prothrombin International Normalized Ratio
Week 52
|
-0.044 Ratio
Standard Deviation 0.3265
|
-0.120 Ratio
Standard Deviation 0.3889
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in ALT, AST and AP were reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
ALT: Baseline
|
26.7 Units per liter (U/L)
Standard Deviation 9.47
|
28.5 Units per liter (U/L)
Standard Deviation 12.84
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
ALT: Week 8
|
-0.8 Units per liter (U/L)
Standard Deviation 5.57
|
-1.8 Units per liter (U/L)
Standard Deviation 9.99
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
ALT: Week 16
|
-0.2 Units per liter (U/L)
Standard Deviation 6.86
|
-1.6 Units per liter (U/L)
Standard Deviation 7.94
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
ALT: Week 32
|
-0.4 Units per liter (U/L)
Standard Deviation 5.62
|
-2.1 Units per liter (U/L)
Standard Deviation 12.53
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
ALT: Week 52
|
-0.2 Units per liter (U/L)
Standard Deviation 8.11
|
-0.3 Units per liter (U/L)
Standard Deviation 14.04
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
AST: Baseline
|
25.8 Units per liter (U/L)
Standard Deviation 7.40
|
28.3 Units per liter (U/L)
Standard Deviation 20.95
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
AST: Week 8
|
-0.7 Units per liter (U/L)
Standard Deviation 4.92
|
-4.4 Units per liter (U/L)
Standard Deviation 2.37
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
AST: Week 16
|
-0.5 Units per liter (U/L)
Standard Deviation 6.13
|
-3.9 Units per liter (U/L)
Standard Deviation 20.25
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
AST: Week 32
|
0.9 Units per liter (U/L)
Standard Deviation 4.14
|
-4.7 Units per liter (U/L)
Standard Deviation 22.46
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
AST: Week 52
|
-0.6 Units per liter (U/L)
Standard Deviation 6.83
|
-3.2 Units per liter (U/L)
Standard Deviation 24.16
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
AP: Baseline
|
106.4 Units per liter (U/L)
Standard Deviation 83.54
|
100.2 Units per liter (U/L)
Standard Deviation 88.62
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
AP: Week 8
|
-7.6 Units per liter (U/L)
Standard Deviation 19.82
|
-8.5 Units per liter (U/L)
Standard Deviation 18.14
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
AP: Week 16
|
-4.7 Units per liter (U/L)
Standard Deviation 19.20
|
-7.1 Units per liter (U/L)
Standard Deviation 22.54
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
AP: Week 32
|
-10.1 Units per liter (U/L)
Standard Deviation 32.43
|
-1.1 Units per liter (U/L)
Standard Deviation 26.30
|
|
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (AP)
AP: Week 52
|
-12.9 Units per liter (U/L)
Standard Deviation 34.81
|
-7.0 Units per liter (U/L)
Standard Deviation 27.63
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in bilirubin and direct bilirubin was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Bilirubin and Direct Bilirubin
Bilirubin: Baseline
|
14.65 micromole per liter (umol/L)
Standard Deviation 5.815
|
17.28 micromole per liter (umol/L)
Standard Deviation 13.379
|
|
Change From Baseline in Bilirubin and Direct Bilirubin
Bilirubin: Week 8
|
0.62 micromole per liter (umol/L)
Standard Deviation 5.985
|
-1.08 micromole per liter (umol/L)
Standard Deviation 5.693
|
|
Change From Baseline in Bilirubin and Direct Bilirubin
Bilirubin: Week 16
|
1.98 micromole per liter (umol/L)
Standard Deviation 5.799
|
-1.76 micromole per liter (umol/L)
Standard Deviation 7.075
|
|
Change From Baseline in Bilirubin and Direct Bilirubin
Bilirubin: Week 32
|
1.47 micromole per liter (umol/L)
Standard Deviation 5.285
|
0.29 micromole per liter (umol/L)
Standard Deviation 5.052
|
|
Change From Baseline in Bilirubin and Direct Bilirubin
Bilirubin: Week 52
|
0.69 micromole per liter (umol/L)
Standard Deviation 5.778
|
-1.02 micromole per liter (umol/L)
Standard Deviation 5.778
|
|
Change From Baseline in Bilirubin and Direct Bilirubin
Direct Bilirubin: Baseline
|
4.04 micromole per liter (umol/L)
Standard Deviation 1.397
|
4.38 micromole per liter (umol/L)
Standard Deviation 1.719
|
|
Change From Baseline in Bilirubin and Direct Bilirubin
Direct Bilirubin: Week 8
|
-0.06 micromole per liter (umol/L)
Standard Deviation 1.105
|
-0.22 micromole per liter (umol/L)
Standard Deviation 1.149
|
|
Change From Baseline in Bilirubin and Direct Bilirubin
Direct Bilirubin: Week 16
|
0.24 micromole per liter (umol/L)
Standard Deviation 1.088
|
-0.28 micromole per liter (umol/L)
Standard Deviation 1.227
|
|
Change From Baseline in Bilirubin and Direct Bilirubin
Direct Bilirubin: Week 32
|
0.00 micromole per liter (umol/L)
Standard Deviation 1.029
|
-0.04 micromole per liter (umol/L)
Standard Deviation 1.147
|
|
Change From Baseline in Bilirubin and Direct Bilirubin
Direct Bilirubin: Week 52
|
0.28 micromole per liter (umol/L)
Standard Deviation 1.280
|
-0.24 micromole per liter (umol/L)
Standard Deviation 1.228
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in gamma glutamyl transferase was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Gamma Glutamyl Transferase
Baseline
|
67.6 Units per liter (U/L)
Standard Deviation 43.02
|
79.4 Units per liter (U/L)
Standard Deviation 45.89
|
|
Change From Baseline in Gamma Glutamyl Transferase
Week 8
|
-4.8 Units per liter (U/L)
Standard Deviation 13.22
|
-5.5 Units per liter (U/L)
Standard Deviation 12.56
|
|
Change From Baseline in Gamma Glutamyl Transferase
Week 16
|
-4.4 Units per liter (U/L)
Standard Deviation 13.79
|
0.7 Units per liter (U/L)
Standard Deviation 27.43
|
|
Change From Baseline in Gamma Glutamyl Transferase
Week 32
|
-1.3 Units per liter (U/L)
Standard Deviation 13.39
|
-5.3 Units per liter (U/L)
Standard Deviation 23.29
|
|
Change From Baseline in Gamma Glutamyl Transferase
Week 52
|
-3.2 Units per liter (U/L)
Standard Deviation 22.40
|
-6.7 Units per liter (U/L)
Standard Deviation 21.31
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here, N (number of participants analyzed) signifies participants evaluable for this outcome measure. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in creatinine was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=67 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Creatinine
Baseline
|
78.1 micromole/liter (umol/L)
Standard Deviation 14.36
|
78.9 micromole/liter (umol/L)
Standard Deviation 17.42
|
|
Change From Baseline in Creatinine
Week 8
|
-2.0 micromole/liter (umol/L)
Standard Deviation 7.49
|
-6.2 micromole/liter (umol/L)
Standard Deviation 7.49
|
|
Change From Baseline in Creatinine
Week 16
|
-1.1 micromole/liter (umol/L)
Standard Deviation 10.72
|
-0.3 micromole/liter (umol/L)
Standard Deviation 12.46
|
|
Change From Baseline in Creatinine
Week 32
|
2.2 micromole/liter (umol/L)
Standard Deviation 10.81
|
-1.8 micromole/liter (umol/L)
Standard Deviation 13.46
|
|
Change From Baseline in Creatinine
Week 52
|
-1.5 micromole/liter (umol/L)
Standard Deviation 9.52
|
0.4 micromole/liter (umol/L)
Standard Deviation 10.00
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in urea nitrogen was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Urea Nitrogen
Baseline
|
5.26 millimoles per liter (mmol/L)
Standard Deviation 1.402
|
5.08 millimoles per liter (mmol/L)
Standard Deviation 1.350
|
|
Change From Baseline in Urea Nitrogen
Week 8
|
-0.30 millimoles per liter (mmol/L)
Standard Deviation 0.989
|
-0.09 millimoles per liter (mmol/L)
Standard Deviation 1.217
|
|
Change From Baseline in Urea Nitrogen
Week 16
|
-0.04 millimoles per liter (mmol/L)
Standard Deviation 1.043
|
0.06 millimoles per liter (mmol/L)
Standard Deviation 1.278
|
|
Change From Baseline in Urea Nitrogen
Week 32
|
0.02 millimoles per liter (mmol/L)
Standard Deviation 0.955
|
-0.25 millimoles per liter (mmol/L)
Standard Deviation 1.274
|
|
Change From Baseline in Urea Nitrogen
Week 52
|
-0.06 millimoles per liter (mmol/L)
Standard Deviation 1.251
|
0.04 millimoles per liter (mmol/L)
Standard Deviation 1.101
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in urate was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Urate
Baseline
|
360.0 umol/L
Standard Deviation 70.95
|
372.7 umol/L
Standard Deviation 88.25
|
|
Change From Baseline in Urate
Week 8
|
-0.8 umol/L
Standard Deviation 40.76
|
-53.6 umol/L
Standard Deviation 40.17
|
|
Change From Baseline in Urate
Week 16
|
2.8 umol/L
Standard Deviation 40.13
|
-37.8 umol/L
Standard Deviation 40.01
|
|
Change From Baseline in Urate
Week 32
|
16.0 umol/L
Standard Deviation 39.35
|
-56.7 umol/L
Standard Deviation 53.18
|
|
Change From Baseline in Urate
Week 52
|
1.1 umol/L
Standard Deviation 49.36
|
-25.8 umol/L
Standard Deviation 54.39
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in glucose, cholesterol, triglycerides, sodium, potassium, chloride and calcium was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Glucose: Baseline
|
4.97 mmol/L
Standard Deviation 0.772
|
5.15 mmol/L
Standard Deviation 0.868
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Glucose: Week 8
|
0.00 mmol/L
Standard Deviation 1.028
|
-0.46 mmol/L
Standard Deviation 0.914
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Glucose: Week 16
|
0.17 mmol/L
Standard Deviation 1.153
|
-0.04 mmol/L
Standard Deviation 1.022
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Glucose: Week 32
|
0.24 mmol/L
Standard Deviation 0.911
|
-0.12 mmol/L
Standard Deviation 0.850
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Glucose: Week 52
|
-0.03 mmol/L
Standard Deviation 0.883
|
-0.28 mmol/L
Standard Deviation 1.193
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Cholesterol: Baseline
|
3.653 mmol/L
Standard Deviation 0.7454
|
3.705 mmol/L
Standard Deviation 0.6676
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Cholesterol: Week 8
|
-0.182 mmol/L
Standard Deviation 0.3808
|
-0.238 mmol/L
Standard Deviation 0.3807
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Cholesterol: Week 16
|
-0.065 mmol/L
Standard Deviation 0.3994
|
-0.190 mmol/L
Standard Deviation 0.5139
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Cholesterol: Week 32
|
0.060 mmol/L
Standard Deviation 0.5185
|
-0.059 mmol/L
Standard Deviation 0.5364
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Cholesterol: Week 52
|
-0.065 mmol/L
Standard Deviation 0.4308
|
-0.093 mmol/L
Standard Deviation 0.4243
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Triglycerides: Baseline
|
1.126 mmol/L
Standard Deviation 0.4787
|
1.057 mmol/L
Standard Deviation 0.4233
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Triglycerides: Week 8
|
-0.061 mmol/L
Standard Deviation 0.5950
|
-0.071 mmol/L
Standard Deviation 0.3755
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Triglycerides: Week 16
|
-0.099 mmol/L
Standard Deviation 0.3946
|
-0.004 mmol/L
Standard Deviation 0.4244
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Triglycerides: Week 32
|
0.123 mmol/L
Standard Deviation 0.4749
|
0.024 mmol/L
Standard Deviation 0.5126
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Triglycerides: Week 52
|
-0.067 mmol/L
Standard Deviation 0.5191
|
-0.020 mmol/L
Standard Deviation 0.4703
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Sodium: Baseline
|
141.2 mmol/L
Standard Deviation 1.93
|
140.8 mmol/L
Standard Deviation 2.79
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Sodium: Week 8
|
-0.5 mmol/L
Standard Deviation 2.02
|
-0.2 mmol/L
Standard Deviation 2.52
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Sodium: Week 16
|
-1.1 mmol/L
Standard Deviation 2.74
|
-0.6 mmol/L
Standard Deviation 2.94
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Sodium: Week 32
|
-0.7 mmol/L
Standard Deviation 3.23
|
-0.3 mmol/L
Standard Deviation 2.44
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Sodium: Week 52
|
-1.1 mmol/L
Standard Deviation 2.28
|
-1.0 mmol/L
Standard Deviation 2.35
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Potassium: Baseline
|
4.364 mmol/L
Standard Deviation 0.2695
|
4.391 mmol/L
Standard Deviation 0.2885
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Potassium: Week 8
|
-0.074 mmol/L
Standard Deviation 0.3476
|
-0.030 mmol/L
Standard Deviation 0.2876
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Potassium: Week 16
|
-0.013 mmol/L
Standard Deviation 0.3684
|
0.030 mmol/L
Standard Deviation 0.3783
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Potassium: Week 32
|
-0.011 mmol/L
Standard Deviation 0.3957
|
-0.033 mmol/L
Standard Deviation 0.2599
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Potassium: Week 52
|
-0.031 mmol/L
Standard Deviation 0.3354
|
-0.003 mmol/L
Standard Deviation 0.3356
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Chloride: Baseline
|
103.9 mmol/L
Standard Deviation 2.19
|
103.3 mmol/L
Standard Deviation 3.30
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Chloride: Week 8
|
0.2 mmol/L
Standard Deviation 1.71
|
1.3 mmol/L
Standard Deviation 2.33
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Chloride: Week 16
|
-0.4 mmol/L
Standard Deviation 2.88
|
0.3 mmol/L
Standard Deviation 2.75
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Chloride: Week 32
|
-0.1 mmol/L
Standard Deviation 2.37
|
0.3 mmol/L
Standard Deviation 2.28
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Chloride: Week 52
|
0.4 mmol/L
Standard Deviation 2.44
|
0.4 mmol/L
Standard Deviation 2.89
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Calcium: Baseline
|
2.458 mmol/L
Standard Deviation 0.0990
|
2.479 mmol/L
Standard Deviation 0.1114
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Calcium: Week 8
|
-0.006 mmol/L
Standard Deviation 0.1096
|
-0.062 mmol/L
Standard Deviation 0.0999
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Calcium: Week 16
|
-0.002 mmol/L
Standard Deviation 0.0929
|
-0.050 mmol/L
Standard Deviation 0.0943
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Calcium: Week 32
|
0.035 mmol/L
Standard Deviation 0.0987
|
-0.004 mmol/L
Standard Deviation 0.1271
|
|
Change From Baseline in Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride and Calcium
Calcium: Week 52
|
-0.021 mmol/L
Standard Deviation 0.1083
|
-0.035 mmol/L
Standard Deviation 0.1093
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in albumin and protein was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Albumin and Protein
Protein: Week 16
|
-0.3 grams per liter (g/L)
Standard Deviation 4.62
|
-1.9 grams per liter (g/L)
Standard Deviation 4.51
|
|
Change From Baseline in Albumin and Protein
Protein: Week 32
|
-0.2 grams per liter (g/L)
Standard Deviation 4.38
|
-0.3 grams per liter (g/L)
Standard Deviation 4.60
|
|
Change From Baseline in Albumin and Protein
Albumin: Baseline
|
48.64 grams per liter (g/L)
Standard Deviation 3.024
|
49.56 grams per liter (g/L)
Standard Deviation 3.257
|
|
Change From Baseline in Albumin and Protein
Albumin: Week 8
|
-0.74 grams per liter (g/L)
Standard Deviation 2.789
|
-1.73 grams per liter (g/L)
Standard Deviation 2.922
|
|
Change From Baseline in Albumin and Protein
Albumin: Week 16
|
0.61 grams per liter (g/L)
Standard Deviation 2.821
|
-0.82 grams per liter (g/L)
Standard Deviation 3.274
|
|
Change From Baseline in Albumin and Protein
Albumin: Week 32
|
0.79 grams per liter (g/L)
Standard Deviation 3.276
|
0.38 grams per liter (g/L)
Standard Deviation 3.462
|
|
Change From Baseline in Albumin and Protein
Albumin: Week 52
|
-0.08 grams per liter (g/L)
Standard Deviation 3.426
|
-0.53 grams per liter (g/L)
Standard Deviation 3.339
|
|
Change From Baseline in Albumin and Protein
Protein: Baseline
|
75.0 grams per liter (g/L)
Standard Deviation 4.73
|
75.4 grams per liter (g/L)
Standard Deviation 5.24
|
|
Change From Baseline in Albumin and Protein
Protein: Week 8
|
-1.5 grams per liter (g/L)
Standard Deviation 4.28
|
-3.8 grams per liter (g/L)
Standard Deviation 4.38
|
|
Change From Baseline in Albumin and Protein
Protein: Week 52
|
-1.8 grams per liter (g/L)
Standard Deviation 5.42
|
-2.5 grams per liter (g/L)
Standard Deviation 5.56
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in alpha fetoprotein was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Alpha Fetoprotein
Baseline
|
3.145 micrograms per milliliter (ug/L)
Standard Deviation 2.0135
|
3.326 micrograms per milliliter (ug/L)
Standard Deviation 2.2213
|
|
Change From Baseline in Alpha Fetoprotein
Week 8
|
0.006 micrograms per milliliter (ug/L)
Standard Deviation 0.5537
|
-0.061 micrograms per milliliter (ug/L)
Standard Deviation 0.6314
|
|
Change From Baseline in Alpha Fetoprotein
Week 16
|
0.055 micrograms per milliliter (ug/L)
Standard Deviation 0.4373
|
0.160 micrograms per milliliter (ug/L)
Standard Deviation 0.5667
|
|
Change From Baseline in Alpha Fetoprotein
Week 32
|
0.033 micrograms per milliliter (ug/L)
Standard Deviation 0.3911
|
0.191 micrograms per milliliter (ug/L)
Standard Deviation 0.5959
|
|
Change From Baseline in Alpha Fetoprotein
Week 52
|
0.068 micrograms per milliliter (ug/L)
Standard Deviation 0.5003
|
0.240 micrograms per milliliter (ug/L)
Standard Deviation 0.6349
|
SECONDARY outcome
Timeframe: Baseline, Week 8, Week 16, Week 32 and Week 52Population: Safety analysis set included all participants who received at least one dose of study treatment. Here "n" signifies number of participants evaluable at different timepoints.
Change from baseline in cystatin C was reported.
Outcome measures
| Measure |
Placebo
n=69 Participants
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 Participants
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Change From Baseline in Cystatin C
Baseline
|
0.742 milligrams per liter (mg/L)
Standard Deviation 0.1047
|
0.718 milligrams per liter (mg/L)
Standard Deviation 0.1190
|
|
Change From Baseline in Cystatin C
Week 8
|
-0.026 milligrams per liter (mg/L)
Standard Deviation 0.0563
|
-0.019 milligrams per liter (mg/L)
Standard Deviation 0.0782
|
|
Change From Baseline in Cystatin C
Week 16
|
-0.017 milligrams per liter (mg/L)
Standard Deviation 0.1464
|
-0.019 milligrams per liter (mg/L)
Standard Deviation 0.0964
|
|
Change From Baseline in Cystatin C
Week 32
|
-0.038 milligrams per liter (mg/L)
Standard Deviation 0.0659
|
-0.021 milligrams per liter (mg/L)
Standard Deviation 0.0701
|
|
Change From Baseline in Cystatin C
Week 52
|
-0.001 milligrams per liter (mg/L)
Standard Deviation 0.0723
|
0.010 milligrams per liter (mg/L)
Standard Deviation 0.0927
|
Adverse Events
Placebo
Serious events: 9 serious events
Other events: 18 other events
Deaths: 0 deaths
Macitentan
Serious events: 13 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=69 participants at risk
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 participants at risk
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Cardiac disorders
Arrhythmia Supraventricular
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
Cardiac disorders
Atrial Flutter
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Cardiac disorders
Atrial Tachycardia
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
Cardiac disorders
Cardiac Arrest
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Cardiac disorders
Palpitations
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
Cardiac disorders
Supraventricular Tachycardia
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Endocrine disorders
Hyperthyroidism
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
Gastrointestinal disorders
Abdominal Pain
|
1.4%
1/69 • Number of events 2 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
General disorders
Non-Cardiac Chest Pain
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
Hepatobiliary disorders
Congestive Hepatopathy
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
Infections and infestations
Abscess Limb
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
Infections and infestations
Appendicitis
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Infections and infestations
Bronchitis
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Infections and infestations
Cellulitis
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
Infections and infestations
Epstein-Barr Virus Infection
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Infections and infestations
Viral Tonsillitis
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Injury, poisoning and procedural complications
Back Injury
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Injury, poisoning and procedural complications
Clavicle Fracture
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Injury, poisoning and procedural complications
Head Injury
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
Injury, poisoning and procedural complications
Road Traffic Accident
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Investigations
Alanine Aminotransferase Increased
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Investigations
Aspartate Aminotransferase Increased
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Investigations
Heart Rate Increased
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
Investigations
International Normalised Ratio Increased
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine Tumour
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Psychiatric disorders
Mental Status Changes
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Psychiatric disorders
Polydipsia Psychogenic
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Reproductive system and breast disorders
Haemorrhagic Ovarian Cyst
|
1.4%
1/69 • Number of events 1 • Up to 56 weeks
|
0.00%
0/68 • Up to 56 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Surgical and medical procedures
Medical Device Removal
|
0.00%
0/69 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
Other adverse events
| Measure |
Placebo
n=69 participants at risk
Participants received Macitentan matching placebo tablet orally, once daily with or without food starting at Week 0 up to Week 52.
|
Macitentan
n=68 participants at risk
Participants received Macitentan 10 milligrams (mg) tablet, orally once daily with or without food starting at Week 0 up to Week 52.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
5.8%
4/69 • Number of events 4 • Up to 56 weeks
|
2.9%
2/68 • Number of events 2 • Up to 56 weeks
|
|
General disorders
Pyrexia
|
4.3%
3/69 • Number of events 3 • Up to 56 weeks
|
5.9%
4/68 • Number of events 4 • Up to 56 weeks
|
|
Infections and infestations
Nasopharyngitis
|
4.3%
3/69 • Number of events 3 • Up to 56 weeks
|
5.9%
4/68 • Number of events 4 • Up to 56 weeks
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
5.8%
4/69 • Number of events 6 • Up to 56 weeks
|
1.5%
1/68 • Number of events 1 • Up to 56 weeks
|
|
Nervous system disorders
Headache
|
8.7%
6/69 • Number of events 10 • Up to 56 weeks
|
10.3%
7/68 • Number of events 14 • Up to 56 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
- Publication restrictions are in place
Restriction type: OTHER