Trial Outcomes & Findings for A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension (NCT NCT04271475)
NCT ID: NCT04271475
Last Updated: 2025-06-27
Results Overview
Change from baseline in 6MWD as measured by 6-minute walk test (6MWT) at Week 28 was reported. The purpose of the 6MWT was to quantify exercise tolerance and capacity. This standardized test measured the distance an individual was able to walk over a total of six minutes on a hard, flat surface with no obstacles. The goal was for the individual to walk as far as possible in 6 minutes.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
127 participants
Primary outcome timeframe
Baseline (Day 1), Week 28
Results posted on
2025-06-27
Participant Flow
Study comprised of screening, double-blind (DB), open-label (OL) and safety follow-up (FU) periods. The DB period started with an 8-week up-titration phase and lasted until all participants either completed the Week 28 visit or prematurely discontinued the study.
Participant milestones
| Measure |
Double Blind (DB) Period: Macitentan
During the 8-week up-titration phase, participants received macitentan doses orally once daily (QD): 10 mg tablet for 4 weeks followed by 37.5 mg tablet for another 4 weeks prior to reaching the target maintenance phase dose of macitentan 75 mg QD. Participants were to remain on double-blind maintenance treatment until the last participant randomized completed the Week 28 visit. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter post-treatment observation period (PTOP) from DB period last dose until Week 28. Median exposure to DB treatment was 24.50 weeks (minimum: 3.9 weeks; maximum: 160.4 weeks).
|
DB Period: Placebo
Participants received placebo matched to macitentan dose levels during the DB treatment period. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter PTOP from DB period last dose until Week 28. Median exposure to DB treatment was 44 weeks (minimum: 4 weeks; maximum: 147.9 weeks).
|
Open Label (OL) Period: DB Macitentan
Participants who were treated with macitentan in the DB period and had reached the target dose of macitentan 75 mg and completed the DB period as per protocol were considered eligible to transition into the 104-week OL period and they continued macitentan 75 mg tablet orally QD from end of double blind treatment (EODBT) until study termination. Participants who experienced a clinical worsening event confirmed by the clinical event committee (CEC), were allowed to transition to the OL period at any time after Week 28. Median exposure to OL treatment was 72 weeks (minimum: 8.1 weeks; maximum: 84.6 weeks).
|
OL Period: DB Placebo
Participants who were treated with placebo in the DB period and had completed the DB period as per protocol were considered eligible to transition into the 104-week OL period and were up-titrated to the target dose of macitentan 75 mg (macitentan 10 mg for 4 weeks, followed by macitentan 37.5 mg for another 4 weeks). Participants who experienced a clinical worsening event confirmed by the CEC, were allowed to transition to the OL period at any time after Week 28. Median exposure to OL treatment was 72 weeks (minimum: 8.1 weeks; maximum: 84.6 weeks).
|
|---|---|---|---|---|
|
DB Period: Day 1 up to EODBT
STARTED
|
64
|
63
|
0
|
0
|
|
DB Period: Day 1 up to EODBT
COMPLETED
|
1
|
1
|
0
|
0
|
|
DB Period: Day 1 up to EODBT
NOT COMPLETED
|
63
|
62
|
0
|
0
|
|
OL Period:Day 1 Upto End of OL Treatment
STARTED
|
0
|
0
|
1
|
6
|
|
OL Period:Day 1 Upto End of OL Treatment
COMPLETED
|
0
|
0
|
0
|
0
|
|
OL Period:Day 1 Upto End of OL Treatment
NOT COMPLETED
|
0
|
0
|
1
|
6
|
Reasons for withdrawal
| Measure |
Double Blind (DB) Period: Macitentan
During the 8-week up-titration phase, participants received macitentan doses orally once daily (QD): 10 mg tablet for 4 weeks followed by 37.5 mg tablet for another 4 weeks prior to reaching the target maintenance phase dose of macitentan 75 mg QD. Participants were to remain on double-blind maintenance treatment until the last participant randomized completed the Week 28 visit. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter post-treatment observation period (PTOP) from DB period last dose until Week 28. Median exposure to DB treatment was 24.50 weeks (minimum: 3.9 weeks; maximum: 160.4 weeks).
|
DB Period: Placebo
Participants received placebo matched to macitentan dose levels during the DB treatment period. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter PTOP from DB period last dose until Week 28. Median exposure to DB treatment was 44 weeks (minimum: 4 weeks; maximum: 147.9 weeks).
|
Open Label (OL) Period: DB Macitentan
Participants who were treated with macitentan in the DB period and had reached the target dose of macitentan 75 mg and completed the DB period as per protocol were considered eligible to transition into the 104-week OL period and they continued macitentan 75 mg tablet orally QD from end of double blind treatment (EODBT) until study termination. Participants who experienced a clinical worsening event confirmed by the clinical event committee (CEC), were allowed to transition to the OL period at any time after Week 28. Median exposure to OL treatment was 72 weeks (minimum: 8.1 weeks; maximum: 84.6 weeks).
|
OL Period: DB Placebo
Participants who were treated with placebo in the DB period and had completed the DB period as per protocol were considered eligible to transition into the 104-week OL period and were up-titrated to the target dose of macitentan 75 mg (macitentan 10 mg for 4 weeks, followed by macitentan 37.5 mg for another 4 weeks). Participants who experienced a clinical worsening event confirmed by the CEC, were allowed to transition to the OL period at any time after Week 28. Median exposure to OL treatment was 72 weeks (minimum: 8.1 weeks; maximum: 84.6 weeks).
|
|---|---|---|---|---|
|
DB Period: Day 1 up to EODBT
Death
|
1
|
0
|
0
|
0
|
|
DB Period: Day 1 up to EODBT
Physician Decision
|
8
|
1
|
0
|
0
|
|
DB Period: Day 1 up to EODBT
Withdrawal by Subject
|
5
|
4
|
0
|
0
|
|
DB Period: Day 1 up to EODBT
Study Terminated by Sponsor
|
41
|
52
|
0
|
0
|
|
DB Period: Day 1 up to EODBT
Other
|
8
|
5
|
0
|
0
|
|
OL Period:Day 1 Upto End of OL Treatment
Study Terminated by Sponsor
|
0
|
0
|
1
|
5
|
|
OL Period:Day 1 Upto End of OL Treatment
Other
|
0
|
0
|
0
|
1
|
Baseline Characteristics
A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension
Baseline characteristics by cohort
| Measure |
Double Blind (DB) Period: Macitentan
n=64 Participants
During the 8-week up-titration phase, participants received macitentan doses orally once daily (QD): 10 mg tablet for 4 weeks followed by 37.5 mg tablet for another 4 weeks prior to reaching the target maintenance phase dose of macitentan 75 mg QD. Participants were to remain on double-blind maintenance treatment until the last participant randomized completed the Week 28 visit. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter post-treatment observation period (PTOP) from DB period last dose until Week 28. Median exposure to DB treatment was 24.50 weeks (minimum: 3.9 weeks; maximum: 160.4 weeks).
|
DB Period: Placebo
n=63 Participants
Participants received placebo matched to macitentan dose levels during the DB treatment period. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter PTOP from DB period last dose until Week 28. Median exposure to DB treatment was 44 weeks (minimum: 4 weeks; maximum: 147.9 weeks).
|
Total
n=127 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Adults (18-64 years)
|
23 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
Age, Customized
From 65 to 75 years
|
32 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
58 Participants
n=5 Participants
|
|
Age, Customized
Over 75 years
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
37 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
59 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
117 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
18 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
42 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
76 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
ARGENTINA
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
AUSTRALIA
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
BULGARIA
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
CHINA
|
7 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Region of Enrollment
CZECH REPUBLIC
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
DENMARK
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
FRANCE
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
GERMANY
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Region of Enrollment
HUNGARY
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
ISRAEL
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
ITALY
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
JAPAN
|
5 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
LITHUANIA
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
MEXICO
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
POLAND
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
PORTUGAL
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
ROMANIA
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
RUSSIAN FEDERATION
|
5 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
SAUDI ARABIA
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
SINGAPORE
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
SLOVAKIA
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
SOUTH KOREA
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
SPAIN
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
TAIWAN
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
THAILAND
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
TURKEY
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
UNITED KINGDOM
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
UNITED STATES
|
5 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
AgeContinuous
|
64.7 years
STANDARD_DEVIATION 11.69 • n=5 Participants
|
60.3 years
STANDARD_DEVIATION 12.84 • n=7 Participants
|
62.5 years
STANDARD_DEVIATION 12.41 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1), Week 28Population: Full analysis set (FAS) included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via interactive web response system (IWRS). Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
Change from baseline in 6MWD as measured by 6-minute walk test (6MWT) at Week 28 was reported. The purpose of the 6MWT was to quantify exercise tolerance and capacity. This standardized test measured the distance an individual was able to walk over a total of six minutes on a hard, flat surface with no obstacles. The goal was for the individual to walk as far as possible in 6 minutes.
Outcome measures
| Measure |
Double Blind (DB) Period: Macitentan
n=47 Participants
During the 8-week up-titration phase, participants received macitentan doses orally once daily (QD): 10 mg tablet for 4 weeks followed by 37.5 mg tablet for another 4 weeks prior to reaching the target maintenance phase dose of macitentan 75 mg QD. Participants were to remain on double-blind maintenance treatment until the last participant randomized completed the Week 28 visit. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter post-treatment observation period (PTOP) from DB period last dose until Week 28. Median exposure to DB treatment was 24.50 weeks (minimum: 3.9 weeks; maximum: 160.4 weeks).
|
DB Period: Placebo
n=48 Participants
Participants received placebo matched to macitentan dose levels during the DB treatment period. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter PTOP from DB period last dose until Week 28. Median exposure to DB treatment was 44 weeks (minimum: 4 weeks; maximum: 147.9 weeks).
|
|---|---|---|
|
Change From Baseline in 6-minute Walk Distance (6MWD) at Week 28
|
9.7 Meters
Standard Error 5.81
|
25.8 Meters
Standard Error 5.78
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to EODBT: median 24.5 weeks (min 3.9 weeks; max 160.4 weeks) for macitentan, median 44 weeks (min 4 weeks; max 147.9 weeks) for placeboPopulation: FAS included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via IWRS.
Time (months) to first CEC-confirmed clinical worsening up to EODBT were reported. Clinical worsening was defined as the occurrence of at least one of the following events: 1) All-cause death; 2) Heart and/or lung transplantation; 3) Unplanned pulmonary hypertension (PH)-related hospitalization; 4) PH-related deterioration from baseline identified by at least one of the following: a) Persistent increase in World Health Organization functional class (WHO FC) that could not be explained by another cause (for example, viral infection); b) Persistent deterioration by at least 15 percent (%) in exercise capacity; as measured by the 6MWD; c) New or worsened signs or symptoms of right heart failure; 5) Rescue pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA) procedure due to worsening of PH.
Outcome measures
| Measure |
Double Blind (DB) Period: Macitentan
n=64 Participants
During the 8-week up-titration phase, participants received macitentan doses orally once daily (QD): 10 mg tablet for 4 weeks followed by 37.5 mg tablet for another 4 weeks prior to reaching the target maintenance phase dose of macitentan 75 mg QD. Participants were to remain on double-blind maintenance treatment until the last participant randomized completed the Week 28 visit. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter post-treatment observation period (PTOP) from DB period last dose until Week 28. Median exposure to DB treatment was 24.50 weeks (minimum: 3.9 weeks; maximum: 160.4 weeks).
|
DB Period: Placebo
n=63 Participants
Participants received placebo matched to macitentan dose levels during the DB treatment period. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter PTOP from DB period last dose until Week 28. Median exposure to DB treatment was 44 weeks (minimum: 4 weeks; maximum: 147.9 weeks).
|
|---|---|---|
|
Time to First Clinical Event Committee (CEC) Confirmed Clinical Worsening up to End-of Double-blind-treatment (EODBT) Period
|
NA Months
Interval 19.0 to
Median and upper limit of 95% CI were not estimable due to low number of participants with events.
|
NA Months
Median, upper and lower limit of 95% CI were not estimable due to low number of participants with events.
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 28Population: FAS included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via IWRS. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
Number of participants with improvement in WHO FC from baseline to Week 28 were reported. Improvement (decrease) in WHO FC from baseline to Week 28 was calculated for each participant. WHO FC test was used to assess disease severity. Four functional classes (FC) were defined from FC I (no limitation of physical activity) to FC IV (inability to carry out any physical activity without symptoms). For the analysis purpose, these WHO FC class values were transformed to a scale with scores ranged from 1 to 4; where a score of 1 corresponded to WHO FC Class I and a score of 4 corresponded to WHO FC Class IV. The higher scores indicate greater symptom severity or worse impact. Improvement was considered when a participant changed from a higher class to a lower class.
Outcome measures
| Measure |
Double Blind (DB) Period: Macitentan
n=37 Participants
During the 8-week up-titration phase, participants received macitentan doses orally once daily (QD): 10 mg tablet for 4 weeks followed by 37.5 mg tablet for another 4 weeks prior to reaching the target maintenance phase dose of macitentan 75 mg QD. Participants were to remain on double-blind maintenance treatment until the last participant randomized completed the Week 28 visit. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter post-treatment observation period (PTOP) from DB period last dose until Week 28. Median exposure to DB treatment was 24.50 weeks (minimum: 3.9 weeks; maximum: 160.4 weeks).
|
DB Period: Placebo
n=43 Participants
Participants received placebo matched to macitentan dose levels during the DB treatment period. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter PTOP from DB period last dose until Week 28. Median exposure to DB treatment was 44 weeks (minimum: 4 weeks; maximum: 147.9 weeks).
|
|---|---|---|
|
Number of Participants With Improvement in World Health Organization Functional Class (WHO FC) From Baseline to Week 28
|
7 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 28Population: FAS included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via IWRS. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
The cardiopulmonary symptoms domain consisted of 6 items: shortness of breath, fatigue, lack of energy, swelling in ankles or legs, swelling in stomach area and cough and were reported on a 5-point Likert scale from 0 (no symptom at all) to 4 (very severe symptoms), with higher score indicating more symptom. The symptoms part of the PAH-SYMPACT was administered daily over a 7-day period. The recall period of symptom items was the last 24 hours. The mean individual symptom item score was determined for each of the 6 items and a domain score was calculated by summing the mean individual symptom item scores and dividing by the number of items, ranged from 0=no cardiopulmonary symptoms to 4=severe cardiopulmonary symptoms. A higher score indicated more severe symptoms experienced.
Outcome measures
| Measure |
Double Blind (DB) Period: Macitentan
n=28 Participants
During the 8-week up-titration phase, participants received macitentan doses orally once daily (QD): 10 mg tablet for 4 weeks followed by 37.5 mg tablet for another 4 weeks prior to reaching the target maintenance phase dose of macitentan 75 mg QD. Participants were to remain on double-blind maintenance treatment until the last participant randomized completed the Week 28 visit. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter post-treatment observation period (PTOP) from DB period last dose until Week 28. Median exposure to DB treatment was 24.50 weeks (minimum: 3.9 weeks; maximum: 160.4 weeks).
|
DB Period: Placebo
n=35 Participants
Participants received placebo matched to macitentan dose levels during the DB treatment period. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter PTOP from DB period last dose until Week 28. Median exposure to DB treatment was 44 weeks (minimum: 4 weeks; maximum: 147.9 weeks).
|
|---|---|---|
|
Change From Baseline to Week 28 in Pulmonary Arterial Hypertension - Symptoms and Impact (PAH-SYMPACT) - Cardiopulmonary Symptom Domain Score
|
-0.089 score on a scale
Standard Deviation 0.5856
|
-0.060 score on a scale
Standard Deviation 0.3767
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 28Population: FAS included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via IWRS. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
The cardiovascular symptoms domain consisted of 5 items: heart palpitations (fluttering), rapid heartbeat, chest pain, chest tightness, and lightheadedness and were reported on a 5-point Likert scale ranged from 0 (no symptoms at al) to 4 (very severe symptoms), with high score indicating more symptom. The symptoms part of PAH-SYMPACT was administered daily over a 7-day period. The recall period of symptom items was the last 24 hours. An average Cardiovascular Symptoms domain score was determined based on the daily scores of the 5 items. The mean individual symptom item score was determined for each of the 5 items and a domain score was calculated by summing the mean individual symptom item scores and dividing by the number of items, ranged from 0=no cardiovascular symptoms to 4=severe cardiovascular symptoms. Higher score indicated more severe symptoms experienced.
Outcome measures
| Measure |
Double Blind (DB) Period: Macitentan
n=28 Participants
During the 8-week up-titration phase, participants received macitentan doses orally once daily (QD): 10 mg tablet for 4 weeks followed by 37.5 mg tablet for another 4 weeks prior to reaching the target maintenance phase dose of macitentan 75 mg QD. Participants were to remain on double-blind maintenance treatment until the last participant randomized completed the Week 28 visit. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter post-treatment observation period (PTOP) from DB period last dose until Week 28. Median exposure to DB treatment was 24.50 weeks (minimum: 3.9 weeks; maximum: 160.4 weeks).
|
DB Period: Placebo
n=35 Participants
Participants received placebo matched to macitentan dose levels during the DB treatment period. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter PTOP from DB period last dose until Week 28. Median exposure to DB treatment was 44 weeks (minimum: 4 weeks; maximum: 147.9 weeks).
|
|---|---|---|
|
Change From Baseline to Week 28 in PAH-SYMPACT - Cardiovascular Symptom Domain Score
|
-0.141 Score on a scale
Standard Deviation 0.4530
|
-0.101 Score on a scale
Standard Deviation 0.2818
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 28Population: FAS included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via IWRS. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
The EQ-5D-5L was a generic measure of health status. The EQ-5D-5L consisted of 2 parts: EQ-5D-5L utility score (descriptive system) and VAS score. EQ-5D-5L descriptive system consisted of 5-item questionnaire that assessed 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each questionnaire had 5 response levels: 1 =no problems, 2 =slight problems, 3 =moderate problems, 4 =severe problems and 5 =extreme problems. The scores for the 5 questionnaires were used to compute a single utility score which ranged from 0 to 1, where higher score indicated better health state and lower score indicated worse health state. EQ-5D-5L VAS rated current health state on a vertical scale with a score ranged from 0 (worst imaginable health state) to 100 (best imaginable health state), higher scores indicated a better health state.
Outcome measures
| Measure |
Double Blind (DB) Period: Macitentan
n=29 Participants
During the 8-week up-titration phase, participants received macitentan doses orally once daily (QD): 10 mg tablet for 4 weeks followed by 37.5 mg tablet for another 4 weeks prior to reaching the target maintenance phase dose of macitentan 75 mg QD. Participants were to remain on double-blind maintenance treatment until the last participant randomized completed the Week 28 visit. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter post-treatment observation period (PTOP) from DB period last dose until Week 28. Median exposure to DB treatment was 24.50 weeks (minimum: 3.9 weeks; maximum: 160.4 weeks).
|
DB Period: Placebo
n=33 Participants
Participants received placebo matched to macitentan dose levels during the DB treatment period. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter PTOP from DB period last dose until Week 28. Median exposure to DB treatment was 44 weeks (minimum: 4 weeks; maximum: 147.9 weeks).
|
|---|---|---|
|
Change From Baseline to Week 28 in Euro Quality of Life-5-Dimension-5-Level (EQ-5D-5L) Utility Score and Visual Analog Scale (VAS) Score
Utility score
|
0.0472 Score on a scale
Standard Deviation 0.26700
|
0.0050 Score on a scale
Standard Deviation 0.15010
|
|
Change From Baseline to Week 28 in Euro Quality of Life-5-Dimension-5-Level (EQ-5D-5L) Utility Score and Visual Analog Scale (VAS) Score
VAS score
|
5.0 Score on a scale
Standard Deviation 17.65
|
1.6 Score on a scale
Standard Deviation 11.97
|
SECONDARY outcome
Timeframe: From Baseline (Day 1) up to Week 28Population: FAS included all randomized participants assigned to a study intervention and were analyzed according to the intervention they had been assigned to via IWRS. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
Change from baseline to Week 28 in accelerometer-assessed proportion of time spent in moderate to vigorous physical activity were assessed. Daily life physical activity of participant was assessed using accelerometer which was provided to the participant at screening and was worn daily during waking hours up to Week 28. For each scheduled visit, the 14 days prior to the visit were considered as the assessment period for physical activity. To be considered evaluable for a given timepoint, actigraphy variables should have been measured for at least 7 complete days (consecutive or not). A complete day is defined as a record of at least 7 waking hours of data. Proportion of time spent in moderate to vigorous physical activity was the estimated number of minutes spent in moderate or higher physical activity as calculated using the Staudenmayer '15 technique as proportion of the total minutes of algorithmically detected wear time and excluding the minutes that fall within a sleep period.
Outcome measures
| Measure |
Double Blind (DB) Period: Macitentan
n=28 Participants
During the 8-week up-titration phase, participants received macitentan doses orally once daily (QD): 10 mg tablet for 4 weeks followed by 37.5 mg tablet for another 4 weeks prior to reaching the target maintenance phase dose of macitentan 75 mg QD. Participants were to remain on double-blind maintenance treatment until the last participant randomized completed the Week 28 visit. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter post-treatment observation period (PTOP) from DB period last dose until Week 28. Median exposure to DB treatment was 24.50 weeks (minimum: 3.9 weeks; maximum: 160.4 weeks).
|
DB Period: Placebo
n=33 Participants
Participants received placebo matched to macitentan dose levels during the DB treatment period. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter PTOP from DB period last dose until Week 28. Median exposure to DB treatment was 44 weeks (minimum: 4 weeks; maximum: 147.9 weeks).
|
|---|---|---|
|
Change From Baseline to Week 28 in Accelerometer-assessed Proportion of Time Spent in Moderate to Vigorous Physical Activity
|
0.821 Percent of minutes per day
Standard Deviation 3.9249
|
-0.833 Percent of minutes per day
Standard Deviation 4.5160
|
Adverse Events
Double Blind (DB) Period: Macitentan
Serious events: 17 serious events
Other events: 47 other events
Deaths: 1 deaths
DB Period: Placebo
Serious events: 14 serious events
Other events: 38 other events
Deaths: 0 deaths
Open Label (OL) Period: DB Macitentan
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
OL Period: DB Placebo
Serious events: 4 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Double Blind (DB) Period: Macitentan
n=64 participants at risk
During the 8-week up-titration phase, participants received macitentan doses orally once daily (QD): 10 mg tablet for 4 weeks followed by 37.5 mg tablet for another 4 weeks prior to reaching the target maintenance phase dose of macitentan 75 mg QD. Participants were to remain on double-blind maintenance treatment until the last participant randomized completed the Week 28 visit. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter post-treatment observation period (PTOP) from DB period last dose until Week 28. Median exposure to DB treatment was 24.50 weeks (minimum: 3.9 weeks; maximum: 160.4 weeks).
|
DB Period: Placebo
n=63 participants at risk
Participants received placebo matched to macitentan dose levels during the DB treatment period. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter PTOP from DB period last dose until Week 28. Median exposure to DB treatment was 44 weeks (minimum: 4 weeks; maximum: 147.9 weeks).
|
Open Label (OL) Period: DB Macitentan
n=1 participants at risk
Participants who were treated with macitentan in the DB period and had reached the target dose of macitentan 75 mg and completed the DB period as per protocol were considered eligible to transition into the 104-week OL period and they continued macitentan 75 mg tablet orally QD from EODBT until study termination. Participants who experienced a clinical worsening event confirmed by the CEC, were allowed to transition to the OL period at any time after Week 28. Median exposure to OL treatment was 72 weeks (minimum: 8.1 weeks; maximum: 84.6 weeks).
|
OL Period: DB Placebo
n=6 participants at risk
Participants who were treated with placebo in the DB period and had completed the DB period as per protocol were considered eligible to transition into the 104-week OL period and were up-titrated to the target dose of macitentan 75 mg (macitentan 10 mg for 4 weeks, followed by macitentan 37.5 mg for another 4 weeks). Participants who experienced a clinical worsening event confirmed by the CEC, were allowed to transition to the OL period at any time after Week 28. Median exposure to OL treatment was 72 weeks (minimum: 8.1 weeks; maximum: 84.6 weeks).
|
|---|---|---|---|---|
|
Cardiac disorders
Arteriosclerosis Coronary Artery
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Cardiac disorders
Atrial Tachycardia
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Cardiac disorders
Right Ventricular Failure
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Cardiac disorders
Sinus Node Dysfunction
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Ear and labyrinth disorders
Vertigo Positional
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Eye disorders
Cataract
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Gastrointestinal disorders
Dental Caries
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Gastrointestinal disorders
Diverticulum Intestinal Haemorrhagic
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Gastrointestinal disorders
Large Intestine Polyp
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
General disorders
Oedema Peripheral
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Infections and infestations
Diverticulitis
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Infections and infestations
Respiratory Tract Infection
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Infections and infestations
Urosepsis
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Injury, poisoning and procedural complications
Postoperative Hypertension
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Injury, poisoning and procedural complications
Spinal Compression Fracture
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Investigations
Alanine Aminotransferase Increased
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Investigations
Aspartate Aminotransferase Increased
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Metabolism and nutrition disorders
Fluid Retention
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Musculoskeletal and connective tissue disorders
Lumbar Spinal Stenosis
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal Cancer Metastatic
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Nervous system disorders
Hemiparesis
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Nervous system disorders
Transient Ischaemic Attack
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Renal and urinary disorders
Haematuria
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Renal and urinary disorders
Urge Incontinence
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Reproductive system and breast disorders
Abnormal Uterine Bleeding
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Polyps
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Organising Pneumonia
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
3.2%
2/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Hypertension
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
6.3%
4/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
33.3%
2/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Surgical and medical procedures
Ovarian Cystectomy
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Vascular disorders
Haematoma
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Vascular disorders
Post Thrombotic Syndrome
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
Other adverse events
| Measure |
Double Blind (DB) Period: Macitentan
n=64 participants at risk
During the 8-week up-titration phase, participants received macitentan doses orally once daily (QD): 10 mg tablet for 4 weeks followed by 37.5 mg tablet for another 4 weeks prior to reaching the target maintenance phase dose of macitentan 75 mg QD. Participants were to remain on double-blind maintenance treatment until the last participant randomized completed the Week 28 visit. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter post-treatment observation period (PTOP) from DB period last dose until Week 28. Median exposure to DB treatment was 24.50 weeks (minimum: 3.9 weeks; maximum: 160.4 weeks).
|
DB Period: Placebo
n=63 participants at risk
Participants received placebo matched to macitentan dose levels during the DB treatment period. Participants who prematurely discontinued DB study treatment prior to Week 28 but did not withdraw consent were asked to enter PTOP from DB period last dose until Week 28. Median exposure to DB treatment was 44 weeks (minimum: 4 weeks; maximum: 147.9 weeks).
|
Open Label (OL) Period: DB Macitentan
n=1 participants at risk
Participants who were treated with macitentan in the DB period and had reached the target dose of macitentan 75 mg and completed the DB period as per protocol were considered eligible to transition into the 104-week OL period and they continued macitentan 75 mg tablet orally QD from EODBT until study termination. Participants who experienced a clinical worsening event confirmed by the CEC, were allowed to transition to the OL period at any time after Week 28. Median exposure to OL treatment was 72 weeks (minimum: 8.1 weeks; maximum: 84.6 weeks).
|
OL Period: DB Placebo
n=6 participants at risk
Participants who were treated with placebo in the DB period and had completed the DB period as per protocol were considered eligible to transition into the 104-week OL period and were up-titrated to the target dose of macitentan 75 mg (macitentan 10 mg for 4 weeks, followed by macitentan 37.5 mg for another 4 weeks). Participants who experienced a clinical worsening event confirmed by the CEC, were allowed to transition to the OL period at any time after Week 28. Median exposure to OL treatment was 72 weeks (minimum: 8.1 weeks; maximum: 84.6 weeks).
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
7.8%
5/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
3.2%
2/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Blood and lymphatic system disorders
Iron Deficiency Anaemia
|
9.4%
6/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
3.2%
2/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Cardiac disorders
Palpitations
|
3.1%
2/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
6.3%
4/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Gastrointestinal disorders
Nausea
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
6.3%
4/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Gastrointestinal disorders
Stomatitis
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
General disorders
Fatigue
|
6.2%
4/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
4.8%
3/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
General disorders
Oedema Peripheral
|
28.1%
18/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
7.9%
5/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
General disorders
Pyrexia
|
6.2%
4/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
4.8%
3/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
General disorders
Swelling
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Infections and infestations
Bronchitis
|
4.7%
3/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
6.3%
4/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Infections and infestations
Covid-19
|
23.4%
15/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
22.2%
14/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Infections and infestations
Nasopharyngitis
|
4.7%
3/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
12.7%
8/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
6.3%
4/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Injury, poisoning and procedural complications
Ligament Sprain
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
3.2%
2/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
100.0%
1/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Investigations
Haemoglobin Decreased
|
10.9%
7/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Metabolism and nutrition disorders
Fluid Retention
|
6.2%
4/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Metabolism and nutrition disorders
Iron Deficiency
|
3.1%
2/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.7%
3/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
4.8%
3/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Nervous system disorders
Dizziness
|
7.8%
5/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
4.8%
3/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Nervous system disorders
Headache
|
14.1%
9/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
15.9%
10/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Nervous system disorders
Memory Impairment
|
0.00%
0/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.8%
5/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
9.5%
6/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.9%
7/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
7.9%
5/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.6%
1/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
3.2%
2/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
12.5%
8/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
|
Vascular disorders
Hypotension
|
14.1%
9/64 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
1.6%
1/63 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
0.00%
0/1 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
16.7%
1/6 • DB period:DB Day 1 to 30 days post EODBT (median exposure[ME]:24.5 weeks[wks], [min 3.9 wks; max 160.4 wks] on macitentan, ME:44 wks [min 4 wks; max 147.9 wks] on placebo); OL period: OL Day 1 to study termination (ME:72 wks [min 8.1 wks; max 84.6 wks]).
Safety analysis was based on safety analysis set which included all participants who received at least one dose of study intervention in this study and were analysed according to the intervention they actually received.
|
Additional Information
Clinical Science Director CP
Actelion Pharmaceuticals Ltd
Phone: 844-434-4210
Email: [email protected]
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 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 to allow for filing of a patent application.
- Publication restrictions are in place
Restriction type: OTHER