Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 23 of 637 for:    Russian Federation | Chile

Selexipag (ACT-293987) in Pulmonary Arterial Hypertension (GRIPHON)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01106014
Recruitment Status : Completed
First Posted : April 19, 2010
Results First Posted : March 1, 2016
Last Update Posted : January 11, 2018
Sponsor:
Information provided by (Responsible Party):
Actelion

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Pulmonary Arterial Hypertension
Interventions Drug: Selexipag
Drug: Placebo
Enrollment 1156
Recruitment Details A total of 1351 patients were screened from 181 sites in 39 countries worldwide. Of these, 1156 were randomized
Pre-assignment Details Screening assessments were performed up to a maximum of 28 days before baseline
Arm/Group Title SELEXIPAG PLACEBO
Hide Arm/Group Description During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose < 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues. Matching placebo was administered orally following the same administration schedule as described for selexipag
Period Title: Overall Study
Started 574 582
Completed 289 252
Not Completed 285 330
Reason Not Completed
Morbidity or Mortality primary endpoint             155             242
Adverse Event             78             42
Withdrawal by Subject             43             37
Administrative reason             7             6
Lost to Follow-up             2             3
Arm/Group Title Selexipag Placebo Total
Hide Arm/Group Description During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose < 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues. Matching placebo was administered orally following the same administration schedule as described for selexipag Total of all reporting groups
Overall Number of Baseline Participants 574 582 1156
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 574 participants 582 participants 1156 participants
48.2  (15.19) 47.9  (15.55) 48.1  (15.37)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 574 participants 582 participants 1156 participants
Female
457
  79.6%
466
  80.1%
923
  79.8%
Male
117
  20.4%
116
  19.9%
233
  20.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 574 participants 582 participants 1156 participants
Caucasion / White 376 375 751
Asian 125 120 245
Hispanic 51 63 114
Black 13 14 27
Other 9 10 19
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 574 participants 582 participants 1156 participants
Western Europe & Australia 161 160 321
Eastern Europe 149 155 304
Asia 115 113 228
North America 95 98 193
Latin America 54 56 110
PAH etiology   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 574 participants 582 participants 1156 participants
Idiopathic 312 337 649
Heritable 13 13 26
Associated with connective tissue disease 167 167 334
Assoc. with corrected (>=12Mo) congenital shunts 60 50 110
Associated with drug or toxin exposure 17 10 27
Associated with HIV infection 5 5 10
[1]
Measure Description: Number of patients in each PAH etiology category
Modified NYHA/WHO Functional class (FC)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 574 participants 582 participants 1156 participants
FC I 4 5 9
FC II 274 255 529
FC III 293 314 607
FC IV 3 8 11
[1]
Measure Description: Number of patients in each NYHA/WHO Functional class (FC) at screening. The WHO FC ranges from I to IV, with higher ranges indicating more severe functional restrictions
PAH medications at baseline   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 574 participants 582 participants 1156 participants
None 112 124 236
Endothelin Receptor Agonists (ERA) 94 76 170
Phosphodiesterase type 5 inhibitors (PDE5-I) 189 185 374
ERA and PDE5I in combination 179 197 376
[1]
Measure Description: Number of patients receiving PAH background medication at the time of study drug start
Time since PAH diagnosis  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 574 participants 582 participants 1156 participants
0.9
(0.0 to 37.3)
1.1
(0.0 to 38.9)
1.0
(0.0 to 38.9)
6-minute walk distance (6MWD) at baseline  
Median (Full Range)
Unit of measure:  Meters
Number Analyzed 574 participants 582 participants 1156 participants
376
(90 to 482)
369
(50 to 515)
372
(50 to 515)
1.Primary Outcome
Title Time From Randomization to the First Morbidity Event or Death (All Causes) up to 7 Days After the Last Study Drug Intake
Hide Description

Time from randomization to the first occurrence of a morbidity event or death (all causes) was analyzed with the Kaplan-Meier method (event-free KM estimates at different time points).

Morbidity event was defined as any of the following events confirmed by the Critical Event committee:

  • Hospitalization for worsening of pulmonary arterial hypertension (PAH),
  • Worsening of PAH resulting in need for lung transplantation or balloon atrial septostomy,
  • Initiation of parenteral prostanoid therapy or chronic oxygen therapy due to worsening of PAH,
  • Disease progression which was defined by a decrease in 6-minute walk distance from baseline (>=15%, confirmed by a 2nd test on a different day) combined with worsening of WHO FC for patients belonging to WHO FC II/III at baseline, or combined with the need for additional PAH-specific therapy for patients belonging to WHO FC III/IV at baseline.

Note: The number of patients at risk decreased over time but this cannot be captured below

Time Frame Up to 7 days after end of double-blind treatment (maximum: 4.3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The primary endpoint was analyzed using the full analysis set, which includes all randomized patients evaluated according to the study drug to which they have been randomized (intention-to treat analysis set).
Arm/Group Title Selexipag Placebo
Hide Arm/Group Description:
During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose < 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues
Matching placebo was administered orally following the same administration schedule as described for selexipag
Overall Number of Participants Analyzed 574 582
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients free of events
KM estimate at Month 6
91.2
(88.5 to 93.4)
81.7
(78.2 to 84.7)
KM estimate at Month 12
83.1
(79.5 to 86.1)
70.6
(66.6 to 74.3)
KM estimate at Month 18
75.5
(71.2 to 79.2)
61.3
(56.8 to 65.5)
KM estimate at Month 24
67.9
(63.0 to 72.4)
53.9
(49.0 to 58.5)
KM estimate at Month 30
61.9
(56.3 to 66.9)
49.3
(44.2 to 54.3)
KM estimate at Month 36
58.2
(51.7 to 64.1)
41.7
(35.2 to 48.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Selexipag, Placebo
Comments The primary analysis was performed on the Full Analysis Set by a one-sided unstratified log-rank test
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments one-sided p-value
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.6
Confidence Interval (2-Sided) 99%
0.46 to 0.78
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) at Trough
Hide Description The 6-minute walk distance test (6MWD) is a non-encouraged test performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. If the patient was used to taking bronchodilators before a walk, he/she was given them 5 to 30 min before the test. Also if the patient was on chronic oxygen therapy, oxygen was given at their standard rate during the test. Absolute change from baseline to Week 26 in 6MWD was measured at trough, i.e., either on the next day after the last study drug administration or at least 12 hours after study drug administration if on the same day.
Time Frame Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Selexipag Placebo
Hide Arm/Group Description:
During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose &lt; 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues
Matching placebo was administered orally following the same administration schedule as described for selexipag
Overall Number of Participants Analyzed 574 582
Median (Full Range)
Unit of Measure: Meters
6MWD at baseline - Overall
376
(90 to 482)
369
(50 to 515)
6MWD at Week 26- Overall
370
(0 to 617)
346
(0 to 650)
6MWD Change from baseline at Week 26
4
(-448 to 260)
-9
(-438 to 262)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Selexipag, Placebo
Comments Non-parametric ANCOVA with 6MWD as covariate at baseline. Missing values were imputed based on the following imputation rules: 1) if patient was unable to walk at week 26, 0 meter was imputed, 2) if rule 1 did not apply, the second lowest observed 6MWD value (10 meters) at Week 26 was imputed. Missing values were imputed for 21.6% of the subjects.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0027
Comments One-sided p-value of the nonparametric ANCOVA, adjusted for 6-minute walk distance at baseline
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 12
Confidence Interval (2-Sided) 99%
1 to 24
Estimation Comments Point estimate and 2-sided 99% CI for location shift using the HodgesLehmann method
3.Secondary Outcome
Title Absence of Worsening From Baseline to Week 26 in Modified NYHA/WHO Functional Class (WHO FC)
Hide Description [Not Specified]
Time Frame Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Patients with WHO FC IV at baseline were excluded from this analysis as they could not shift to a worse category
Arm/Group Title Selexipag Placebo
Hide Arm/Group Description:
During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose &lt; 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues
Matching placebo was administered orally following the same administration schedule as described for selexipag
Overall Number of Participants Analyzed 571 574
Measure Type: Number
Unit of Measure: Percentage of patients
77.8 74.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Selexipag, Placebo
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments It was assumed that the probabilities for absence of worsening in WHO FC at Week 26 were the same for both treatment groups
Statistical Test of Hypothesis P-Value 0.2843
Comments Cochran-Mantel-Haenszel test stratified by WHO FC at baseline. For patients with missing NYHA/WHO FC at Week 26, the NYHA/WHO FC is considered as having worsened from baseline at Week 26. Missing values were imputed for 18.3% of subjects .
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 1.161
Confidence Interval (2-Sided) 99%
0.811 to 1.664
Estimation Comments [Not Specified]
Time Frame From baseline up to up to 7 days after end of treatment (EOT)
Adverse Event Reporting Description Median duration of exposure to study drug was 70.7 weeks (range: 0.3–216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7–192.0 weeks) in the placebo group
 
Arm/Group Title Selexipag Placebo
Hide Arm/Group Description This group includes patients who received at least one dose of selexipag. One subject who was randomized to placebo received a single dose of 8 tablets of selexipag due to an error in the dispensation of the medication bottle. Therefore, this patient was assigned to the selexipag group in the safety analysis set. This group includes patients who received at least one dose of placebo. Four patients who were randomized to placebo never received the drugs and another patient received selexipag by mistake (see Selexipag group for more details). Therefore, these patients were excluded from the placebo group in the safety analysis set.
All-Cause Mortality
Selexipag Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Selexipag Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   252/575 (43.83%)      272/577 (47.14%)    
Blood and lymphatic system disorders     
ANAEMIA  1  5/575 (0.87%)  7 3/577 (0.52%)  5
HAEMORRHAGIC ANAEMIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
IDIOPATHIC THROMBOCYTOPENIC PURPURA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
LEUKOPENIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
NEUTROPENIA  1  0/575 (0.00%)  0 1/577 (0.17%)  1
THROMBOCYTOPENIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Cardiac disorders     
ACUTE CORONARY SYNDROME  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ACUTE MYOCARDIAL INFARCTION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
ACUTE RIGHT VENTRICULAR FAILURE  1  2/575 (0.35%)  2 5/577 (0.87%)  5
ANGINA PECTORIS  1  1/575 (0.17%)  1 1/577 (0.17%)  2
ARRHYTHMIA  1  1/575 (0.17%)  1 1/577 (0.17%)  1
ATRIAL FIBRILLATION  1  7/575 (1.22%)  9 4/577 (0.69%)  5
ATRIAL FLUTTER  1  3/575 (0.52%)  3 5/577 (0.87%)  5
ATRIAL TACHYCARDIA  1  1/575 (0.17%)  1 2/577 (0.35%)  4
ATRIAL THROMBOSIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
ATRIOVENTRICULAR BLOCK SECOND DEGREE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
BRADYARRHYTHMIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
BRADYCARDIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CARDIAC ARREST  1  2/575 (0.35%)  2 4/577 (0.69%)  4
CARDIAC FAILURE  1  1/575 (0.17%)  1 2/577 (0.35%)  2
CARDIAC FAILURE CONGESTIVE  1  2/575 (0.35%)  2 1/577 (0.17%)  1
CARDIO-RESPIRATORY ARREST  1  2/575 (0.35%)  2 2/577 (0.35%)  2
CARDIOGENIC SHOCK  1  1/575 (0.17%)  1 2/577 (0.35%)  2
CARDIOPULMONARY FAILURE  1  3/575 (0.52%)  3 1/577 (0.17%)  1
CHRONIC RIGHT VENTRICULAR FAILURE  1  2/575 (0.35%)  3 2/577 (0.35%)  2
COR PULMONALE  1  1/575 (0.17%)  2 0/577 (0.00%)  0
COR PULMONALE ACUTE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
COR PULMONALE CHRONIC  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CORONARY ARTERY INSUFFICIENCY  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CORONARY ARTERY OCCLUSION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CORONARY ARTERY STENOSIS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
CYANOSIS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
MYOCARDIAL INFARCTION  1  1/575 (0.17%)  1 1/577 (0.17%)  1
PALPITATIONS  1  2/575 (0.35%)  2 1/577 (0.17%)  1
RIGHT VENTRICULAR DYSFUNCTION  1  0/575 (0.00%)  0 1/577 (0.17%)  2
RIGHT VENTRICULAR FAILURE  1  34/575 (5.91%)  42 41/577 (7.11%)  49
SUPRAVENTRICULAR TACHYCARDIA  1  1/575 (0.17%)  1 4/577 (0.69%)  6
TACHYCARDIA  1  1/575 (0.17%)  2 0/577 (0.00%)  0
VENTRICULAR FIBRILLATION  1  3/575 (0.52%)  3 0/577 (0.00%)  0
VENTRICULAR TACHYCARDIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Ear and labyrinth disorders     
VERTIGO  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Endocrine disorders     
AUTOIMMUNE THYROIDITIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
BASEDOW'S DISEASE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
HYPERTHYROIDISM  1  1/575 (0.17%)  1 0/577 (0.00%)  0
HYPOTHYROIDISM  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Eye disorders     
CATARACT  1  2/575 (0.35%)  3 0/577 (0.00%)  0
CHOROIDITIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
MACULOPATHY  1  1/575 (0.17%)  1 0/577 (0.00%)  0
VISION BLURRED  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Gastrointestinal disorders     
ABDOMINAL DISCOMFORT  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ABDOMINAL DISTENSION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
ABDOMINAL HERNIA  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ABDOMINAL PAIN  1  5/575 (0.87%)  6 4/577 (0.69%)  4
ANAL HAEMORRHAGE  1  0/575 (0.00%)  0 1/577 (0.17%)  2
ASCITES  1  2/575 (0.35%)  2 0/577 (0.00%)  0
COLITIS ISCHAEMIC  1  0/575 (0.00%)  0 1/577 (0.17%)  1
DIARRHOEA  1  3/575 (0.52%)  3 3/577 (0.52%)  3
DUODENAL ULCER  1  1/575 (0.17%)  1 0/577 (0.00%)  0
DYSPEPSIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
ENTERITIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
ENTEROCELE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
GASTRITIS  1  3/575 (0.52%)  3 1/577 (0.17%)  1
GASTROINTESTINAL ANGIODYSPLASIA HAEMORRHAGIC  1  1/575 (0.17%)  1 1/577 (0.17%)  1
GASTROINTESTINAL HAEMORRHAGE  1  3/575 (0.52%)  3 3/577 (0.52%)  4
GASTROOESOPHAGEAL REFLUX DISEASE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
HAEMATEMESIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
HAEMATOCHEZIA  1  0/575 (0.00%)  0 2/577 (0.35%)  2
ILEUS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
INTESTINAL OBSTRUCTION  1  0/575 (0.00%)  0 1/577 (0.17%)  2
LARGE INTESTINE POLYP  1  1/575 (0.17%)  1 0/577 (0.00%)  0
MELAENA  1  0/575 (0.00%)  0 1/577 (0.17%)  1
NAUSEA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
NECROTISING COLITIS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
OESOPHAGEAL OBSTRUCTION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
OESOPHAGEAL VARICES HAEMORRHAGE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PANCREATITIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PANCREATITIS ACUTE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
SIGMOIDITIS  1  0/575 (0.00%)  0 1/577 (0.17%)  2
UPPER GASTROINTESTINAL HAEMORRHAGE  1  2/575 (0.35%)  3 1/577 (0.17%)  1
VOMITING  1  2/575 (0.35%)  2 2/577 (0.35%)  2
General disorders     
ASTHENIA  1  2/575 (0.35%)  2 0/577 (0.00%)  0
CHEST DISCOMFORT  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CHEST PAIN  1  6/575 (1.04%)  7 6/577 (1.04%)  8
DEATH  1  1/575 (0.17%)  1 2/577 (0.35%)  2
EXERCISE TOLERANCE DECREASED  1  1/575 (0.17%)  1 1/577 (0.17%)  1
FATIGUE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
GENERAL PHYSICAL HEALTH DETERIORATION  1  0/575 (0.00%)  0 1/577 (0.17%)  2
IMPAIRED HEALING  1  0/575 (0.00%)  0 1/577 (0.17%)  1
INFLUENZA LIKE ILLNESS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
MULTI-ORGAN FAILURE  1  1/575 (0.17%)  1 2/577 (0.35%)  2
NON-CARDIAC CHEST PAIN  1  0/575 (0.00%)  0 1/577 (0.17%)  1
OEDEMA PERIPHERAL  1  3/575 (0.52%)  4 4/577 (0.69%)  5
PYREXIA  1  0/575 (0.00%)  0 1/577 (0.17%)  1
SUDDEN CARDIAC DEATH  1  1/575 (0.17%)  1 0/577 (0.00%)  0
SUDDEN DEATH  1  5/575 (0.87%)  5 4/577 (0.69%)  4
Hepatobiliary disorders     
ACUTE HEPATIC FAILURE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
CHOLANGITIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CHOLECYSTITIS ACUTE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CHOLELITHIASIS  1  1/575 (0.17%)  1 2/577 (0.35%)  2
HEPATIC CIRRHOSIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
HEPATIC CYST  1  1/575 (0.17%)  1 0/577 (0.00%)  0
HEPATIC MASS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
HEPATORENAL SYNDROME  1  0/575 (0.00%)  0 1/577 (0.17%)  1
NODULAR REGENERATIVE HYPERPLASIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Immune system disorders     
HYPERSENSITIVITY  1  0/575 (0.00%)  0 1/577 (0.17%)  1
LUNG TRANSPLANT REJECTION  1  0/575 (0.00%)  0 1/577 (0.17%)  1
SARCOIDOSIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
SECONDARY IMMUNODEFICIENCY  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Infections and infestations     
ABDOMINAL INFECTION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
ABSCESS INTESTINAL  1  1/575 (0.17%)  1 0/577 (0.00%)  0
ABSCESS LIMB  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ABSCESS ORAL  1  0/575 (0.00%)  0 1/577 (0.17%)  1
APPENDICITIS PERFORATED  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ATYPICAL PNEUMONIA  1  0/575 (0.00%)  0 1/577 (0.17%)  2
BRONCHITIS  1  6/575 (1.04%)  7 4/577 (0.69%)  4
BRONCHOPNEUMONIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CATHETER SITE INFECTION  1  0/575 (0.00%)  0 1/577 (0.17%)  1
CELLULITIS  1  3/575 (0.52%)  4 3/577 (0.52%)  3
CLOSTRIDIUM DIFFICILE COLITIS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
CYSTITIS ESCHERICHIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
DIABETIC GANGRENE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
DIVERTICULITIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
ENTEROCOLITIS VIRAL  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ERYSIPELAS  1  2/575 (0.35%)  2 0/577 (0.00%)  0
GASTROENTERITIS  1  1/575 (0.17%)  1 3/577 (0.52%)  3
HEPATITIS C  1  0/575 (0.00%)  0 1/577 (0.17%)  1
HERPES ZOSTER  1  1/575 (0.17%)  1 0/577 (0.00%)  0
INFECTION  1  0/575 (0.00%)  0 1/577 (0.17%)  1
INFLUENZA  1  2/575 (0.35%)  3 0/577 (0.00%)  0
LOBAR PNEUMONIA  1  0/575 (0.00%)  0 2/577 (0.35%)  2
LOCALISED INFECTION  1  1/575 (0.17%)  2 0/577 (0.00%)  0
LOWER RESPIRATORY TRACT INFECTION  1  4/575 (0.70%)  4 4/577 (0.69%)  4
LUNG ABSCESS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
LUNG INFECTION  1  4/575 (0.70%)  4 2/577 (0.35%)  2
LYMPHANGITIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
NASOPHARYNGITIS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
OSTEOMYELITIS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
PARAINFLUENZAE VIRUS INFECTION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PAROTITIS  1  0/575 (0.00%)  0 1/577 (0.17%)  3
PERITONITIS  1  0/575 (0.00%)  0 2/577 (0.35%)  2
PILONIDAL CYST  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PNEUMONIA  1  17/575 (2.96%)  18 25/577 (4.33%)  30
PNEUMONIA BACTERIAL  1  1/575 (0.17%)  1 0/577 (0.00%)  0
POST PROCEDURAL INFECTION  1  0/575 (0.00%)  0 1/577 (0.17%)  1
POST PROCEDURAL SEPSIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PYELONEPHRITIS  1  2/575 (0.35%)  2 1/577 (0.17%)  1
PYELONEPHRITIS ACUTE  1  3/575 (0.52%)  3 0/577 (0.00%)  0
PYELONEPHRITIS CHRONIC  1  1/575 (0.17%)  1 0/577 (0.00%)  0
RESPIRATORY TRACT INFECTION  1  4/575 (0.70%)  5 3/577 (0.52%)  3
SEPSIS  1  3/575 (0.52%)  3 1/577 (0.17%)  1
SEPTIC SHOCK  1  3/575 (0.52%)  3 1/577 (0.17%)  1
STAPHYLOCOCCAL SEPSIS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
TOOTH ABSCESS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
TOOTH INFECTION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
TRACHEOBRONCHITIS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
UPPER RESPIRATORY TRACT INFECTION  1  4/575 (0.70%)  4 3/577 (0.52%)  3
URINARY TRACT INFECTION  1  2/575 (0.35%)  2 1/577 (0.17%)  1
VIRAL INFECTION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Injury, poisoning and procedural complications     
ACCIDENT  1  1/575 (0.17%)  1 1/577 (0.17%)  1
ACETABULUM FRACTURE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
BRAIN HERNIATION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CRANIOCEREBRAL INJURY  1  1/575 (0.17%)  1 0/577 (0.00%)  0
FALL  1  3/575 (0.52%)  3 6/577 (1.04%)  8
FEMORAL NECK FRACTURE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
FEMUR FRACTURE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
FOOT FRACTURE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
GINGIVAL INJURY  1  0/575 (0.00%)  0 1/577 (0.17%)  1
HEAD INJURY  1  1/575 (0.17%)  1 0/577 (0.00%)  0
INJURY  1  0/575 (0.00%)  0 1/577 (0.17%)  1
JAW FRACTURE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
JOINT DISLOCATION  1  1/575 (0.17%)  1 1/577 (0.17%)  1
LIGAMENT SPRAIN  1  1/575 (0.17%)  1 0/577 (0.00%)  0
LIP INJURY  1  0/575 (0.00%)  0 1/577 (0.17%)  1
LOWER LIMB FRACTURE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
LUMBAR VERTEBRAL FRACTURE  1  1/575 (0.17%)  1 2/577 (0.35%)  2
MULTIPLE INJURIES  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PELVIC FRACTURE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
POST PROCEDURAL COMPLICATION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
POST PROCEDURAL HAEMATOMA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
POST PROCEDURAL HAEMORRHAGE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PROCEDURAL HAEMORRHAGE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
PUBIS FRACTURE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
RESPIRATORY FUME INHALATION DISORDER  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ROAD TRAFFIC ACCIDENT  1  4/575 (0.70%)  5 2/577 (0.35%)  2
SUBDURAL HAEMATOMA  1  2/575 (0.35%)  2 0/577 (0.00%)  0
TOXICITY TO VARIOUS AGENTS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
TRAUMATIC FRACTURE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
VACCINATION COMPLICATION  1  0/575 (0.00%)  0 1/577 (0.17%)  1
VASCULAR PROCEDURE COMPLICATION  1  0/575 (0.00%)  0 1/577 (0.17%)  1
VASCULAR PSEUDOANEURYSM  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  1/575 (0.17%)  1 1/577 (0.17%)  1
ASPARTATE AMINOTRANSFERASE INCREASED  1  1/575 (0.17%)  1 0/577 (0.00%)  0
BRAIN NATRIURETIC PEPTIDE INCREASED  1  0/575 (0.00%)  0 1/577 (0.17%)  1
CARDIAC INDEX DECREASED  1  1/575 (0.17%)  1 1/577 (0.17%)  1
CATHETERISATION CARDIAC  1  3/575 (0.52%)  3 1/577 (0.17%)  1
INTERNATIONAL NORMALISED RATIO INCREASED  1  0/575 (0.00%)  0 1/577 (0.17%)  1
INVESTIGATION  1  2/575 (0.35%)  3 1/577 (0.17%)  1
LIVER FUNCTION TEST ABNORMAL  1  0/575 (0.00%)  0 1/577 (0.17%)  1
OXYGEN SATURATION DECREASED  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PULMONARY ARTERIAL PRESSURE INCREASED  1  0/575 (0.00%)  0 1/577 (0.17%)  1
PULMONARY ARTERIAL WEDGE PRESSURE INCREASED  1  0/575 (0.00%)  0 1/577 (0.17%)  1
RED BLOOD CELL COUNT INCREASED  1  1/575 (0.17%)  1 0/577 (0.00%)  0
TRANSPLANT EVALUATION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
WALKING DISTANCE TEST ABNORMAL  1  0/575 (0.00%)  0 1/577 (0.17%)  1
WEIGHT DECREASED  1  1/575 (0.17%)  1 0/577 (0.00%)  0
WEIGHT INCREASED  1  0/575 (0.00%)  0 1/577 (0.17%)  1
Metabolism and nutrition disorders     
DEHYDRATION  1  2/575 (0.35%)  2 2/577 (0.35%)  2
DIABETES MELLITUS INADEQUATE CONTROL  1  0/575 (0.00%)  0 1/577 (0.17%)  1
DYSLIPIDAEMIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
ELECTROLYTE IMBALANCE  1  2/575 (0.35%)  2 1/577 (0.17%)  1
FLUID OVERLOAD  1  0/575 (0.00%)  0 1/577 (0.17%)  1
FLUID RETENTION  1  1/575 (0.17%)  1 1/577 (0.17%)  1
GOUT  1  0/575 (0.00%)  0 1/577 (0.17%)  1
HYPOGLYCAEMIA  1  1/575 (0.17%)  1 1/577 (0.17%)  2
HYPONATRAEMIC SYNDROME  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Musculoskeletal and connective tissue disorders     
BACK PAIN  1  2/575 (0.35%)  2 0/577 (0.00%)  0
CHONDROCALCINOSIS PYROPHOSPHATE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
CREST SYNDROME  1  0/575 (0.00%)  0 1/577 (0.17%)  2
CRYSTAL ARTHROPATHY  1  0/575 (0.00%)  0 1/577 (0.17%)  1
INTERVERTEBRAL DISC PROTRUSION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
MIXED CONNECTIVE TISSUE DISEASE  1  2/575 (0.35%)  2 0/577 (0.00%)  0
MYALGIA  1  2/575 (0.35%)  2 0/577 (0.00%)  0
OSTEOPOROSIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
OSTEOPOROTIC FRACTURE  1  1/575 (0.17%)  2 0/577 (0.00%)  0
PAIN IN EXTREMITY  1  2/575 (0.35%)  2 0/577 (0.00%)  0
POLYMYOSITIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
RHEUMATOID ARTHRITIS  1  0/575 (0.00%)  0 2/577 (0.35%)  4
STILL'S DISEASE ADULT ONSET  1  1/575 (0.17%)  2 0/577 (0.00%)  0
SYSTEMIC LUPUS ERYTHEMATOSUS  1  5/575 (0.87%)  5 1/577 (0.17%)  1
SYSTEMIC SCLEROSIS  1  1/575 (0.17%)  1 2/577 (0.35%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
BASAL CELL CARCINOMA  1  1/575 (0.17%)  2 0/577 (0.00%)  0
BREAST CANCER  1  1/575 (0.17%)  1 3/577 (0.52%)  5
BREAST CANCER RECURRENT  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CEREBRAL HAEMANGIOMA  1  0/575 (0.00%)  0 1/577 (0.17%)  1
COLORECTAL CANCER METASTATIC  1  1/575 (0.17%)  1 0/577 (0.00%)  0
DIFFUSE LARGE B-CELL LYMPHOMA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
HEPATIC NEOPLASM  1  1/575 (0.17%)  1 0/577 (0.00%)  0
LUNG ADENOCARCINOMA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
LYMPHANGIOSIS CARCINOMATOSA  1  1/575 (0.17%)  2 0/577 (0.00%)  0
MALIGNANT MELANOMA  1  0/575 (0.00%)  0 1/577 (0.17%)  1
Nervous system disorders     
AGEUSIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
APHASIA  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ATAXIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
AUTONOMIC NERVOUS SYSTEM IMBALANCE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
CEREBELLAR SYNDROME  1  0/575 (0.00%)  0 1/577 (0.17%)  1
CEREBRAL INFARCTION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CEREBROVASCULAR ACCIDENT  1  1/575 (0.17%)  1 0/577 (0.00%)  0
DEMYELINATION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
DIZZINESS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
HAEMORRHAGE INTRACRANIAL  1  1/575 (0.17%)  1 0/577 (0.00%)  0
HEADACHE  1  2/575 (0.35%)  2 0/577 (0.00%)  0
HYPOGLYCAEMIC UNCONSCIOUSNESS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ISCHAEMIC STROKE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
LOSS OF CONSCIOUSNESS  1  1/575 (0.17%)  1 1/577 (0.17%)  1
MENTAL IMPAIRMENT  1  1/575 (0.17%)  1 0/577 (0.00%)  0
MIGRAINE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
PARKINSON'S DISEASE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
POST HERPETIC NEURALGIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PRESYNCOPE  1  2/575 (0.35%)  2 1/577 (0.17%)  1
SUBARACHNOID HAEMORRHAGE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
SYNCOPE  1  10/575 (1.74%)  13 20/577 (3.47%)  23
THALAMIC INFARCTION  1  0/575 (0.00%)  0 1/577 (0.17%)  1
TRANSIENT ISCHAEMIC ATTACK  1  2/575 (0.35%)  2 0/577 (0.00%)  0
VOCAL CORD PARALYSIS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
Pregnancy, puerperium and perinatal conditions     
PREGNANCY  1  1/575 (0.17%)  1 1/577 (0.17%)  1
RUPTURED ECTOPIC PREGNANCY  1  0/575 (0.00%)  0 1/577 (0.17%)  1
Psychiatric disorders     
ALCOHOLISM  1  0/575 (0.00%)  0 1/577 (0.17%)  3
MENTAL STATUS CHANGES  1  0/575 (0.00%)  0 1/577 (0.17%)  1
SCHIZOAFFECTIVE DISORDER  1  0/575 (0.00%)  0 1/577 (0.17%)  1
SOMNAMBULISM  1  0/575 (0.00%)  0 1/577 (0.17%)  1
STRESS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
SUICIDE ATTEMPT  1  0/575 (0.00%)  0 1/577 (0.17%)  1
Renal and urinary disorders     
ACUTE PRERENAL FAILURE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
ANURIA  1  0/575 (0.00%)  0 1/577 (0.17%)  1
LUPUS NEPHRITIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
OLIGURIA  1  1/575 (0.17%)  2 0/577 (0.00%)  0
RENAL FAILURE  1  1/575 (0.17%)  1 1/577 (0.17%)  1
RENAL FAILURE ACUTE  1  6/575 (1.04%)  6 6/577 (1.04%)  6
URETHRAL STENOSIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Reproductive system and breast disorders     
CERVICAL DYSPLASIA  1  2/575 (0.35%)  2 0/577 (0.00%)  0
CYSTOCELE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ENDOMETRIOSIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
MENORRHAGIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
OVARIAN CYST  1  0/575 (0.00%)  0 1/577 (0.17%)  1
OVARIAN CYST RUPTURED  1  0/575 (0.00%)  0 1/577 (0.17%)  1
Respiratory, thoracic and mediastinal disorders     
ACUTE LUNG INJURY  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ACUTE RESPIRATORY FAILURE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
ASTHMA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CHRONIC OBSTRUCTIVE PULMONARY DISEASE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
DYSPNOEA  1  17/575 (2.96%)  21 13/577 (2.25%)  17
DYSPNOEA EXERTIONAL  1  1/575 (0.17%)  2 2/577 (0.35%)  2
EPISTAXIS  1  4/575 (0.70%)  4 4/577 (0.69%)  4
HAEMOPTYSIS  1  5/575 (0.87%)  5 5/577 (0.87%)  7
HYPOXIA  1  1/575 (0.17%)  1 3/577 (0.52%)  4
INTERSTITIAL LUNG DISEASE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ORGANISING PNEUMONIA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
ORTHOPNOEA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PULMONARY ARTERIAL HYPERTENSION  1  83/575 (14.43%)  106 127/577 (22.01%)  183
PULMONARY ARTERY DILATATION  1  0/575 (0.00%)  0 1/577 (0.17%)  1
PULMONARY EMBOLISM  1  4/575 (0.70%)  4 3/577 (0.52%)  3
PULMONARY HAEMORRHAGE  1  0/575 (0.00%)  0 1/577 (0.17%)  1
PULMONARY HYPERTENSION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PULMONARY INFARCTION  1  0/575 (0.00%)  0 1/577 (0.17%)  1
PULMONARY OEDEMA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PULMONARY VENO-OCCLUSIVE DISEASE  1  2/575 (0.35%)  2 1/577 (0.17%)  2
RESPIRATORY FAILURE  1  0/575 (0.00%)  0 3/577 (0.52%)  3
RESPIRATORY GAS EXCHANGE DISORDER  1  1/575 (0.17%)  1 0/577 (0.00%)  0
SLEEP APNOEA SYNDROME  1  0/575 (0.00%)  0 1/577 (0.17%)  1
TACHYPNOEA  1  0/575 (0.00%)  0 1/577 (0.17%)  1
Skin and subcutaneous tissue disorders     
DERMATITIS CONTACT  1  0/575 (0.00%)  0 1/577 (0.17%)  1
DERMATOMYOSITIS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
PAIN OF SKIN  1  1/575 (0.17%)  1 0/577 (0.00%)  0
RASH  1  0/575 (0.00%)  0 1/577 (0.17%)  1
SCLERODERMA ASSOCIATED DIGITAL ULCER  1  1/575 (0.17%)  1 1/577 (0.17%)  1
SKIN ULCER  1  1/575 (0.17%)  1 0/577 (0.00%)  0
TELANGIECTASIA  1  0/575 (0.00%)  0 1/577 (0.17%)  1
Surgical and medical procedures     
BARIATRIC GASTRIC BALLOON INSERTION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
BLADDER NECK SUSPENSION  1  0/575 (0.00%)  0 1/577 (0.17%)  1
CARDIAC PACEMAKER INSERTION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CARDIOVERSION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CERVICAL CONISATION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
CHOLECYSTECTOMY  1  0/575 (0.00%)  0 1/577 (0.17%)  2
DRUG THERAPY CHANGED  1  1/575 (0.17%)  1 1/577 (0.17%)  1
GLAUCOMA SURGERY  1  0/575 (0.00%)  0 1/577 (0.17%)  1
HAEMODIALYSIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
LUNG TRANSPLANT  1  2/575 (0.35%)  2 1/577 (0.17%)  1
MASTECTOMY  1  1/575 (0.17%)  1 0/577 (0.00%)  0
NASAL SEPTAL OPERATION  1  0/575 (0.00%)  0 1/577 (0.17%)  1
SALPINGECTOMY  1  0/575 (0.00%)  0 1/577 (0.17%)  1
SKIN NEOPLASM EXCISION  1  1/575 (0.17%)  2 0/577 (0.00%)  0
STEM CELL TRANSPLANT  1  1/575 (0.17%)  2 0/577 (0.00%)  0
TURBINECTOMY  1  0/575 (0.00%)  0 1/577 (0.17%)  1
URETHRAL OPERATION  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Vascular disorders     
CIRCULATORY COLLAPSE  1  2/575 (0.35%)  2 1/577 (0.17%)  1
DEEP VEIN THROMBOSIS  1  2/575 (0.35%)  3 1/577 (0.17%)  1
EXTREMITY NECROSIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
FLUSHING  1  1/575 (0.17%)  1 0/577 (0.00%)  0
HAEMATOMA  1  1/575 (0.17%)  1 0/577 (0.00%)  0
HAEMODYNAMIC INSTABILITY  1  0/575 (0.00%)  0 1/577 (0.17%)  1
HYPERTENSION  1  0/575 (0.00%)  0 1/577 (0.17%)  1
HYPOTENSION  1  3/575 (0.52%)  3 3/577 (0.52%)  3
HYPOVOLAEMIC SHOCK  1  0/575 (0.00%)  0 1/577 (0.17%)  1
ORTHOSTATIC HYPOTENSION  1  1/575 (0.17%)  1 1/577 (0.17%)  1
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE  1  1/575 (0.17%)  1 0/577 (0.00%)  0
PERIPHERAL ARTERY THROMBOSIS  1  0/575 (0.00%)  0 1/577 (0.17%)  1
PERIPHLEBITIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
THROMBOPHLEBITIS SUPERFICIAL  1  1/575 (0.17%)  1 0/577 (0.00%)  0
VASCULITIS  1  2/575 (0.35%)  2 0/577 (0.00%)  0
VENA CAVA THROMBOSIS  1  1/575 (0.17%)  1 0/577 (0.00%)  0
VENOUS INSUFFICIENCY  1  0/575 (0.00%)  0 1/577 (0.17%)  1
VENOUS THROMBOSIS LIMB  1  1/575 (0.17%)  1 0/577 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Selexipag Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   544/575 (94.61%)      486/577 (84.23%)    
Blood and lymphatic system disorders     
ANAEMIA  1  43/575 (7.48%)  53 28/577 (4.85%)  37
Cardiac disorders     
PALPITATIONS  1  32/575 (5.57%)  40 31/577 (5.37%)  41
Gastrointestinal disorders     
ABDOMINAL PAIN  1  44/575 (7.65%)  54 29/577 (5.03%)  37
ABDOMINAL PAIN UPPER  1  34/575 (5.91%)  39 32/577 (5.55%)  38
DIARRHOEA  1  242/575 (42.09%)  375 109/577 (18.89%)  137
NAUSEA  1  192/575 (33.39%)  265 107/577 (18.54%)  136
VOMITING  1  103/575 (17.91%)  143 48/577 (8.32%)  53
General disorders     
ASTHENIA  1  29/575 (5.04%)  33 24/577 (4.16%)  27
CHEST PAIN  1  34/575 (5.91%)  37 39/577 (6.76%)  54
FATIGUE  1  46/575 (8.00%)  54 58/577 (10.05%)  72
OEDEMA PERIPHERAL  1  77/575 (13.39%)  90 100/577 (17.33%)  138
Infections and infestations     
BRONCHITIS  1  42/575 (7.30%)  46 41/577 (7.11%)  49
NASOPHARYNGITIS  1  75/575 (13.04%)  105 63/577 (10.92%)  95
UPPER RESPIRATORY TRACT INFECTION  1  72/575 (12.52%)  100 79/577 (13.69%)  119
URINARY TRACT INFECTION  1  24/575 (4.17%)  30 30/577 (5.20%)  34
Metabolism and nutrition disorders     
DECREASED APPETITE  1  34/575 (5.91%)  38 19/577 (3.29%)  23
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  62/575 (10.78%)  82 44/577 (7.63%)  57
BACK PAIN  1  34/575 (5.91%)  36 35/577 (6.07%)  38
MYALGIA  1  90/575 (15.65%)  120 34/577 (5.89%)  37
PAIN IN EXTREMITY  1  95/575 (16.52%)  142 46/577 (7.97%)  62
PAIN IN JAW  1  148/575 (25.74%)  188 36/577 (6.24%)  38
Nervous system disorders     
DIZZINESS  1  85/575 (14.78%)  111 85/577 (14.73%)  106
HEADACHE  1  374/575 (65.04%)  649 189/577 (32.76%)  261
SYNCOPE  1  30/575 (5.22%)  35 34/577 (5.89%)  42
Respiratory, thoracic and mediastinal disorders     
COUGH  1  56/575 (9.74%)  67 67/577 (11.61%)  87
DYSPNOEA  1  79/575 (13.74%)  100 110/577 (19.06%)  143
PULMONARY ARTERIAL HYPERTENSION  1  46/575 (8.00%)  64 84/577 (14.56%)  141
Vascular disorders     
FLUSHING  1  69/575 (12.00%)  80 29/577 (5.03%)  31
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Clinical trial disclosure desk
Organization: Actelion Pharmaceuticals Ltd
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01106014     History of Changes
Other Study ID Numbers: AC-065A302
First Submitted: April 2, 2010
First Posted: April 19, 2010
Results First Submitted: February 2, 2016
Results First Posted: March 1, 2016
Last Update Posted: January 11, 2018