PORTICO: PORtopulmonary Hypertension Treatment wIth maCitentan - a randOmized Clinical Trial
Sponsor
Actelion (Industry)
Overall Status
Completed
CT.gov ID
NCT02382016
Collaborator
(none)
85
52
2
40.3
1.6
0
Study Details
Study Description
Brief Summary
24-week study to evaluate the efficacy and safety of macitentan for the treatment of portopulmonary hypertension.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
85 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled, Prospective, Multicenter, Parallel Group Study to Assess the Safety and Efficacy of Macitentan in Patients With Portopulmonary Hypertension
Actual Study Start Date
:
Jun 23, 2015
Actual Primary Completion Date
:
Oct 25, 2017
Actual Study Completion Date
:
Oct 31, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Investigational treatment Macitentan film-coated tablet 10 mg once daily. |
Drug: Macitentan
Macitentan film-coated tablet 10 mg once daily.
Other Names:
|
| Placebo Comparator: Placebo Matching placebo tablet once daily. |
Other: Placebo
Matching placebo tablet once daily.
|
Outcome Measures
Primary Outcome Measures
- Relative Change From Baseline to Week 12 in Pulmonary Vascular Resistance (PVR). [From enrollment/baseline to Week 12 in the Double Blind (DB) treatment period]
The relative change from baseline to Week 12 in PVR is expressed as a ratio of Week 12 to baseline PVR.
Secondary Outcome Measures
- Change From Baseline to Week 12 in 6-minute Walk Distance (6MWD) [From enrollment/baseline to Week 12 in the DB treatment period]
The purpose of the six minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.
- Change From Baseline to Week 12 in WHO Functional Class (FC) [From enrollment/baseline to Week 12 in the DB treatment period]
Changes from baseline to Week 12 in WHO FC were dichotomized as worsening (i.e., change > 0) versus no change or improvement (i.e., change ≤ 0). Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing a flight of stairs, grocery shopping, or making the bed). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest (e.g. dyspnea and/or fatigue) and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure.
- Change From Baseline to Week 12 in the Biomarker N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) [From enrollment/baseline to Week 12 in the DB treatment period]
NT-proBNP functions as a strong indicator of prognosis in patients with pulmonary hypertension (PH). The relative change from baseline to Week 12 in NT-proBNP is expressed as a ratio of Week 12 to baseline NT-proBNP.
- Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP) [From enrollment/baseline to Week 12 in the DB treatment period]
mRAP is the mean blood pressure in the right atrium of the heart.
- Change From Baseline to Week 12 in Mean Pulmonary Artery Pressure (mPAP) [From enrollment/baseline to Week 12 in the DB treatment period]
mPAP is the mean blood pressure inside the pulmonary artery which moves the blood from the heart to the lungs. Monitoring of mPAP can detect small changes in the function of the heart.
- Change From Baseline to Week 12 in Cardiac Index [From enrollment/baseline to Week 12 in the DB treatment period]
The cardiac index is an assessment of the function of the heart and relates the cardiac output to the patient's body size (the patient's body surface area).
- Change From Baseline to Week 12 in Total Pulmonary Resistance (TPR) [From enrollment/baseline to Week 12 in the DB treatment period]
TPR is the resistance the pulmonary circulation that must be overcome in order for the blood flow to occur. It takes into account the blood pressure in the pulmonary arteries and the cardiac output. It is an important measurement to monitor the function of the pulmonary circulation and detect disease progression or improvement.
- Change From Baseline to Week 12 in Mixed Venous Oxygen Saturation (SVO2) [From enrollment/baseline to Week 12 in the DB treatment period]
SVO2 help assess tissue oxygen delivery. It describes the percentage of oxygen bound to hemoglobin in the blood which returns to the heart. This reflects the amount of residual oxygen in the blood after oxygen extraction by the tissues throughout the body.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Main Inclusion Criteria:
-
Male or female of at least 18 years of age
-
Confirmed diagnosis of portopulmonary hypertension
Main Exclusion Criteria:
-
Severe hepatic impairment
-
Severe obstructive or restrictive lung disease
-
Pulmonary veno-occlusive disease
-
Systolic blood pressure (SBP) < 90 mmHg at Screening
-
ALT/AST >= 3 x ULN
-
Bilirubin >= 3 mg/dL at Screening
-
Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of results
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic -Clinical Studies Unit | Phoenix | Arizona | United States | 85054 |
| 2 | UCSD | La Jolla | California | United States | 92093 |
| 3 | David Geffen School of Medicine, UCLA | Los Angeles | California | United States | 90025-1690 |
| 4 | Keck School of Medicine | Los Angeles | California | United States | 90033 |
| 5 | UCSF | San Francisco | California | United States | 91413-2204 |
| 6 | University of Colorado Health Sciences Center Aurora | Aurora | Colorado | United States | 80045 |
| 7 | University of Florida - Divison of Pulmonary Critical Care & Sleep | Gainesville | Florida | United States | 32610 |
| 8 | University of Florida College of Medicine | Jacksonville | Florida | United States | 32209 |
| 9 | Mayo Clinic Florida - Pulmonary Dept. | Jacksonville | Florida | United States | 32224 |
| 10 | University of Miami | Miami | Florida | United States | 33136 |
| 11 | South Miami Hospital | South Miami | Florida | United States | 33143 |
| 12 | Emory Healthcare | Atlanta | Georgia | United States | 30322 |
| 13 | Piedmont Healthcare | Austell | Georgia | United States | 30106 |
| 14 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 15 | Indiana University | Indianapolis | Indiana | United States | 46202 |
| 16 | Kentuckiana Pulmonary Associates | Louisville | Kentucky | United States | 40202 |
| 17 | Boston University | Boston | Massachusetts | United States | 02118 |
| 18 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 19 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 20 | University of New Mexico Health Science Center | Albuquerque | New Mexico | United States | 87131-0001 |
| 21 | University of Cincinnati | Cincinnati | Ohio | United States | 45267 |
| 22 | Cleveland Clinic - Department of Cardiovascular Medicine | Cleveland | Ohio | United States | 44195 |
| 23 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 24 | UPMC Montefiore | Pittsburgh | Pennsylvania | United States | 15213 |
| 25 | Baylor University Medical Center | Dallas | Texas | United States | 75226 |
| 26 | University of Texas Southwestern Medical Center Division of NeuroCritical Care 75390-8550 | Dallas | Texas | United States | 75390-8550 |
| 27 | Methodist Hospital | Houston | Texas | United States | 77030 |
| 28 | Methodist Hospital | San Antonio | Texas | United States | 78229 |
| 29 | University of Wisconsin-Madison | Madison | Wisconsin | United States | 53705-2281 |
| 30 | Servico de Hipertensao Pulmonar - Complexo Hospitalar Santa Casa Irmandade Santa de Misericordia de Porto Alegre | Porto Alegre | Brazil | 92020-090 | |
| 31 | Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP) | Sao Paulo | Brazil | 05403-000 | |
| 32 | Lékařská fakulta a Všeobecná fakultní nemocnice v Praze, II. Interní klinika kardiologie a angiologie U | Prague | Czechia | 128 08 | |
| 33 | IKEM (Institut klinické a experimentální medicíny, Institute for Clinical and Experimental Medicine) | Prague | Czechia | 140 21 | |
| 34 | CHRU Hôpital Cavale Blanche Brest | Brest | Bretagne | France | 29609 |
| 35 | CHRU de Grenoble, Hôpital Albert Michallon | Grenoble | Rhône- Alpes | France | 38043 |
| 36 | CHU Côte de Nacre, Service de Pneumologie | Caen | France | 14033 | |
| 37 | Hôpital cardiologique, Service de cardiologie 59037 Lille Cedex" | Lille | France | 59037 | |
| 38 | Hôpital Cardiologique et Pneumologique Louis Pradel 69677 Bron cedex" | Lyon | France | 69677 | |
| 39 | Hôpital Kremlin Bicêtre Service de Pneumologie | Paris | France | 94275 | |
| 40 | Hôpital Pontchaillou - CHU Rennes Service de Cardiologie et des Maladies Vasculaires Rennes Cedex 9 35033" | Rennes | France | 35033 | |
| 41 | CHU Rouen | Rouen | France | 76031 | |
| 42 | CHU Toulouse - Hôpital Larrey Hôpital de Jour et Semaine | Toulouse | France | 31059 | |
| 43 | Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden | Dresden | Germany | 01307 | |
| 44 | Universitätsklinikum Giessen und Marburg GmbH Justus-Liebig Universität Giessen 35392 | Giessen | Germany | 35392 | |
| 45 | Medizinische Hochschule Hannover, Abteilung Pneumologie | Hannover | Germany | 30625 | |
| 46 | Thoraxklinik des Universitätsklinikums Heidelberg Zentrum für pulmonale Hypertonie Studienkoordination | Heidelberg | Germany | 69126 | |
| 47 | Universitätsklinikum Leipzig, Department Innere Medizin, Abteilung Pneumologie | Leipzig | Germany | 04103 | |
| 48 | Hospital Clinico i Provincial Servicio de Neumología | Barcelona | Spain | 08036 | |
| 49 | Hospital Universitario12 Octubre | Madrid | Spain | 28041 | |
| 50 | NHS Greater Glasgow and Clyde Trust | Glasgow | Scotland | United Kingdom | G11 6NT |
| 51 | The Royal Free Hospital/ Cardiology Department | London | United Kingdom | NW3 2QG | |
| 52 | Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital | Sheffield | United Kingdom | S10 2RX |
Sponsors and Collaborators
- Actelion
Investigators
- Study Director: Loïc Perchenet, PhD, Actelion
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Actelion
ClinicalTrials.gov Identifier:
NCT02382016
Other Study ID Numbers:
- AC-055-404
First Posted:
Mar 6, 2015
Last Update Posted:
Nov 5, 2019
Last Verified:
Oct 1, 2019
Study Results
Participant Flow
| Recruitment Details | Participants at 39 sites in 7 countries were screened and were randomized at 36 sites in these 7 countries (Brazil, Czech Republic, France, Germany, Spain, UK and US). |
|---|---|
| Pre-assignment Detail | A total of 119 participants were screened and 85 participants were randomized (43 to macitentan 10 mg once daily and 42 to matching placebo) and received double-blind (DB) study treatment. Overall, 80 participants who completed DB treatment period entered the open-label (OL) treatment period and 33 participants in open-label extension (OLE) period. |
| Arm/Group Title | Macitentan 10 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. Participants who completed DB treatment period continued to receive macitentan 10 mg for 12 weeks (up to Week 24) in OL treatment period . Participants (who were randomized at French sites) who completed the core phase of the study as scheduled and opted to continue receiving OL study treatment continued to receive macitentan 10 mg in OLE period. | Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. Participants who completed DB treatment period were administered with macitentan 10 mg for 12 weeks (up to Week 24) in OL treatment period. Participants who were randomized at French sites who completed the core study as scheduled and opted to continue receiving OL study treatment continued to receive macitentan 10mg in OLE period. |
| Period Title: Double-blind (DB) Treatment Period | ||
| STARTED | 43 | 42 |
| COMPLETED | 39 | 41 |
| NOT COMPLETED | 4 | 1 |
| Period Title: Double-blind (DB) Treatment Period | ||
| STARTED | 80 | 0 |
| COMPLETED | 71 | 0 |
| NOT COMPLETED | 9 | 0 |
| Period Title: Double-blind (DB) Treatment Period | ||
| STARTED | 33 | 0 |
| COMPLETED | 27 | 0 |
| NOT COMPLETED | 6 | 0 |
Baseline Characteristics
| Arm/Group Title | Macitentan 10 mg | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. | Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. | Total of all reporting groups |
| Overall Participants | 43 | 42 | 85 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
35
81.4%
|
29
69%
|
64
75.3%
|
| >=65 years |
8
18.6%
|
13
31%
|
21
24.7%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
58.0
(8.7)
|
59.0
(9.5)
|
58.5
(9.1)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
21
48.8%
|
20
47.6%
|
41
48.2%
|
| Male |
22
51.2%
|
22
52.4%
|
44
51.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
6
14%
|
6
14.3%
|
12
14.1%
|
| Not Hispanic or Latino |
19
44.2%
|
15
35.7%
|
34
40%
|
| Unknown or Not Reported |
18
41.9%
|
21
50%
|
39
45.9%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Asian |
1
2.3%
|
0
0%
|
1
1.2%
|
| White |
23
53.5%
|
21
50%
|
44
51.8%
|
| Other |
1
2.3%
|
0
0%
|
1
1.2%
|
| Not Applicable |
18
41.9%
|
21
50%
|
39
45.9%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
12
27.9%
|
11
26.2%
|
23
27.1%
|
| Brazil |
2
4.7%
|
3
7.1%
|
5
5.9%
|
| Czech Republic |
1
2.3%
|
3
7.1%
|
4
4.7%
|
| France |
18
41.9%
|
21
50%
|
39
45.9%
|
| Germany |
4
9.3%
|
4
9.5%
|
8
9.4%
|
| Spain |
4
9.3%
|
0
0%
|
4
4.7%
|
| United Kingdom |
2
4.7%
|
0
0%
|
2
2.4%
|
| Pulmonary arterial hypertension (PAH)-specific therapy (Count of Participants) | |||
| Yes |
27
62.8%
|
27
64.3%
|
54
63.5%
|
| No |
16
37.2%
|
15
35.7%
|
31
36.5%
|
| Body Mass Index (BMI) at baseline (Kilogram per meter^2 (Kg/m^2)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Kilogram per meter^2 (Kg/m^2)] |
29.01
(4.79)
|
29.33
(4.04)
|
29.17
(4.41)
|
| Time since portal hypertension diagnosis (Months) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [Months] |
23
|
31
|
25
|
| Time since PAH diagnosis (Months) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [Months] |
7
|
12
|
10
|
| Pulmonary vascular resistance (PVR) at baseline (calculated) (Dyn*sec/cm^5) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Dyn*sec/cm^5] |
552.4
(192.8)
|
521.7
(163.3)
|
537.2
(178.4)
|
Outcome Measures
| Title | Relative Change From Baseline to Week 12 in Pulmonary Vascular Resistance (PVR). |
|---|---|
| Description | The relative change from baseline to Week 12 in PVR is expressed as a ratio of Week 12 to baseline PVR. |
| Time Frame | From enrollment/baseline to Week 12 in the Double Blind (DB) treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Macitentan 10 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. | Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. |
| Measure Participants | 43 | 42 |
| Geometric Mean (95% Confidence Interval) [ratio] |
0.63
|
0.98
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Macitentan 10 mg, Placebo |
|---|---|---|
| Comments | The null hypothesis (change of PVR at Week 12 as a ratio of baseline PVR in subjects treated with placebo or macitentan is the same) is tested on the primary endpoint by means of an analysis of covariance (ANCOVA) model on the log(e) transformed ratio of PVR at Week 12 to baseline PVR. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ANCOVA model adjusted by treatment, background PAH-specific therapy at baseline and region as factors & log-transformed PVR at baseline as a covariate | |
| Method of Estimation | Estimation Parameter | ratio of geometric means |
| Estimated Value | 0.65 | |
| Confidence Interval |
(2-Sided) 95% 0.59 to 0.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 12 in 6-minute Walk Distance (6MWD) |
|---|---|
| Description | The purpose of the six minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. |
| Time Frame | From enrollment/baseline to Week 12 in the DB treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Macitentan 10 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. | Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. |
| Measure Participants | 43 | 42 |
| 6MWD at baseline |
385.8
(99.97)
|
383.2
(108.90)
|
| 6MWD at Week 12 |
392.2
(98.46)
|
380.8
(114.98)
|
| Change of 6MWD from baseline to Week 12 |
6.4
(65.74)
|
-2.4
(43.65)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Macitentan 10 mg, Placebo |
|---|---|---|
| Comments | The main analysis on 6MWD was performed using a mixed-effect model repeated measure (MMRM) adjusted for treatment, visit, region, PAH-specific therapy at baseline, and treatment-by-visit interaction as factors, and baseline 6MWD and WHO functional class (FC) as covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4264 |
| Comments | No adjustment was made for multiplicity for secondary endpoints, therefore all corresponding p-values provided are of an exploratory nature. | |
| Method | mixed-effect model repeated measure | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares (LS) mean difference |
| Estimated Value | 9.73 | |
| Confidence Interval |
(2-Sided) 95% -14.50 to 33.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The estimated value refers to a between-treatment analysis of change from baseline to Week 12 in 6MWD (LS mean difference macitentan 10 mg - placebo). | |
| Title | Change From Baseline to Week 12 in WHO Functional Class (FC) |
|---|---|
| Description | Changes from baseline to Week 12 in WHO FC were dichotomized as worsening (i.e., change > 0) versus no change or improvement (i.e., change ≤ 0). Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing a flight of stairs, grocery shopping, or making the bed). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest (e.g. dyspnea and/or fatigue) and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure. |
| Time Frame | From enrollment/baseline to Week 12 in the DB treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Macitentan 10 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. | Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. |
| Measure Participants | 43 | 42 |
| WHO FC I at baseline |
1
2.3%
|
1
2.4%
|
| WHO FC II at baseline |
27
62.8%
|
23
54.8%
|
| WHO FC III at baseline |
15
34.9%
|
18
42.9%
|
| WHO FC IV at baseline |
0
0%
|
0
0%
|
| WHO FC I at Week 12 |
3
7%
|
4
9.5%
|
| WHO FC II at Week 12 |
27
62.8%
|
23
54.8%
|
| WHO FC III at Week 12 |
13
30.2%
|
15
35.7%
|
| WHO FC IV at Week 12 |
0
0%
|
0
0%
|
| Improved from baseline to Week 12 |
9
20.9%
|
7
16.7%
|
| Worsened from baseline to Week 12 |
6
14%
|
1
2.4%
|
| Unchanged from baseline to Week 12 |
28
65.1%
|
34
81%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Macitentan 10 mg, Placebo |
|---|---|---|
| Comments | A logistic regression model (exact) adjusted for treatment, PAH-specific therapy at baseline, and region as covariates was used to analyze worsening in WHO FC. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1278 |
| Comments | No adjustment was made for multiplicity for secondary endpoints, therefore all corresponding p-values provided are of an exploratory nature. | |
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 6.253 | |
| Confidence Interval |
(2-Sided) 95% 0.714 to 298.376 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 12 in the Biomarker N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) |
|---|---|
| Description | NT-proBNP functions as a strong indicator of prognosis in patients with pulmonary hypertension (PH). The relative change from baseline to Week 12 in NT-proBNP is expressed as a ratio of Week 12 to baseline NT-proBNP. |
| Time Frame | From enrollment/baseline to Week 12 in the DB treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set(FAS): All randomized participants who received at least one dose of study drug in DB treatment, have baseline value for PVR, evaluated As per assigned treatment. Here, 'N'(number of participants analyzed included population included participants with available baseline data. |
| Arm/Group Title | Macitentan 10 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. | Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. |
| Measure Participants | 41 | 40 |
| Geometric Mean (95% Confidence Interval) [ratio] |
0.86
|
1.04
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Macitentan 10 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3951 |
| Comments | No adjustment was made for multiplicity for secondary endpoints, therefore all corresponding p-values provided are of an exploratory nature. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | ratio of geometric means |
| Estimated Value | 0.874 | |
| Confidence Interval |
(2-Sided) 95% 0.639 to 1.196 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP) |
|---|---|
| Description | mRAP is the mean blood pressure in the right atrium of the heart. |
| Time Frame | From enrollment/baseline to Week 12 in the DB treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set(FAS): All randomized participants who received at least one dose of study drug in DB treatment, have baseline value for PVR, evaluated As per assigned treatment. Here, 'N'(number of participants analyzed included population included participants with available baseline data. |
| Arm/Group Title | Macitentan 10 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. | Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. |
| Measure Participants | 42 | 42 |
| mRAP at baseline |
7.3
(3.74)
|
6.7
(3.60)
|
| mRAP at Week 12 |
9.0
(5.32)
|
7.0
(2.93)
|
| Change in mRAP from baseline to Week 12 |
1.6
(5.55)
|
0.3
(3.29)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Macitentan 10 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0637 |
| Comments | No adjustment was made for multiplicity for secondary endpoints, therefore all corresponding p-values provided are of an exploratory nature. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares (LS) mean difference |
| Estimated Value | 1.67 | |
| Confidence Interval |
(2-Sided) 95% -0.10 to 3.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The estimated value refers to a between-treatment analysis of change from baseline to Week 12 in mRAP (LS mean difference macitentan 10 mg - placebo). | |
| Title | Change From Baseline to Week 12 in Mean Pulmonary Artery Pressure (mPAP) |
|---|---|
| Description | mPAP is the mean blood pressure inside the pulmonary artery which moves the blood from the heart to the lungs. Monitoring of mPAP can detect small changes in the function of the heart. |
| Time Frame | From enrollment/baseline to Week 12 in the DB treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Macitentan 10 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. | Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. |
| Measure Participants | 43 | 42 |
| mPAP at baseline |
46.4
(7.89)
|
43.8
(8.52)
|
| mPAP at Week 12 |
40.0
(7.61)
|
44.2
(8.26)
|
| Change in mPAP at Week 12 |
-6.4
(4.94)
|
0.4
(7.04)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Macitentan 10 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | No adjustment was made for multiplicity for secondary endpoints, therefore all corresponding p-values provided are of an exploratory nature. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares (LS) mean difference |
| Estimated Value | -5.99 | |
| Confidence Interval |
(2-Sided) 95% -8.40 to -3.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The estimated value refers to a between-treatment analysis of change from baseline to Week 12 in mPAP (LS mean difference macitentan 10 mg - placebo). | |
| Title | Change From Baseline to Week 12 in Cardiac Index |
|---|---|
| Description | The cardiac index is an assessment of the function of the heart and relates the cardiac output to the patient's body size (the patient's body surface area). |
| Time Frame | From enrollment/baseline to Week 12 in the DB treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Macitentan 10 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. | Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. |
| Measure Participants | 43 | 42 |
| Cardiac index at baseline |
3.1
(0.83)
|
2.9
(0.76)
|
| Cardiac index at Week 12 |
3.7
(1.04)
|
3.0
(0.82)
|
| Change in cardiac index at Week 12 |
0.6
(0.8)
|
0.1
(0.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Macitentan 10 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0009 |
| Comments | No adjustment was made for multiplicity for secondary endpoints, therefore all corresponding p-values provided are of an exploratory nature. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares (LS) mean difference |
| Estimated Value | 0.52 | |
| Confidence Interval |
(2-Sided) 95% 0.22 to 0.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The estimated value refers to a between-treatment analysis of change from baseline to Week 12 in cardiac index (LS mean difference macitentan 10 mg - placebo). | |
| Title | Change From Baseline to Week 12 in Total Pulmonary Resistance (TPR) |
|---|---|
| Description | TPR is the resistance the pulmonary circulation that must be overcome in order for the blood flow to occur. It takes into account the blood pressure in the pulmonary arteries and the cardiac output. It is an important measurement to monitor the function of the pulmonary circulation and detect disease progression or improvement. |
| Time Frame | From enrollment/baseline to Week 12 in the DB treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Macitentan 10 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. | Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. |
| Measure Participants | 43 | 42 |
| TPR at baseline |
689.3
(228.59)
|
671.5
(199.73)
|
| TPR at Week 12 |
489.4
(157.13)
|
653.1
(197.88)
|
| Change in TPR from baseline to Week 12 |
-199.8
(163.06)
|
-18.3
(135.28)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Macitentan 10 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | No adjustment was made for multiplicity for secondary endpoints, therefore all corresponding p-values provided are of an exploratory nature. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares (LS) mean difference |
| Estimated Value | -171.48 | |
| Confidence Interval |
(2-Sided) 95% -223.67 to -119.30 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The estimated value refers to a between-treatment analysis of change from baseline to Week 12 in TPR (LS mean difference macitentan 10 mg - placebo). | |
| Title | Change From Baseline to Week 12 in Mixed Venous Oxygen Saturation (SVO2) |
|---|---|
| Description | SVO2 help assess tissue oxygen delivery. It describes the percentage of oxygen bound to hemoglobin in the blood which returns to the heart. This reflects the amount of residual oxygen in the blood after oxygen extraction by the tissues throughout the body. |
| Time Frame | From enrollment/baseline to Week 12 in the DB treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set(FAS): All randomized participants who received at least one dose of study drug in DB treatment, have baseline value for PVR, evaluated As per assigned treatment. Here, 'N'(number of participants analyzed included population included participants with available baseline data. |
| Arm/Group Title | Macitentan 10 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. | Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. |
| Measure Participants | 41 | 41 |
| SVO2 at baseline |
69.2
(9.87)
|
69.9
(5.34)
|
| SVO2 at Week 12 |
70.3
(7.07)
|
70.7
(8.58)
|
| Change in SVO2 from baseline to Week 12 |
1.1
(6.70)
|
0.8
(7.81)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Macitentan 10 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9844 |
| Comments | No adjustment was made for multiplicity for secondary endpoints, therefore all corresponding p-values provided are of an exploratory nature. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least squares (LS) mean difference |
| Estimated Value | 0.03 | |
| Confidence Interval |
(2-Sided) 95% -2.85 to 2.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The estimated value refers to a between-treatment analysis of change from baseline to Week 12 in SVO2 (LS mean difference macitentan 10 mg - placebo). | |
Adverse Events
| Time Frame | Up to 3.4 years | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The Safety Set (SS) included all participants who received at least one dose of study treatment. | |||||||
| Arm/Group Title | Double-Blind (DB) Period: Macitentan 10 mg | DB Period: Placebo | Open-Label (OL) Period: Macitentan 10 mg | OL Extension Period: Macitentan 10 mg | ||||
| Arm/Group Description | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks during DB treatment period. | Participants received Macitentan matching placebo film-coated tablets orally once daily for 12 weeks during DB treatment period. | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. Participants who completed DB treatment period continued to receive macitentan 10 mg for 12 weeks (up to Week 24) in OL treatment period. | Participants received Macitentan 10 milligram (mg) film-coated tablets orally once daily for 12 weeks in Double-blind treatment period. Participants who completed DB treatment period continued to receive macitentan 10 mg for 12 weeks (up to Week 24) in OL treatment period . Participants (who were randomized at French sites) who completed the core phase of the study as scheduled and opted to continue receiving OL study treatment continued to receive macitentan 10 mg in OLE period. | ||||
All Cause Mortality |
||||||||
| Double-Blind (DB) Period: Macitentan 10 mg | DB Period: Placebo | Open-Label (OL) Period: Macitentan 10 mg | OL Extension Period: Macitentan 10 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/43 (0%) | 0/42 (0%) | 4/80 (5%) | 2/33 (6.1%) | ||||
Serious Adverse Events |
||||||||
| Double-Blind (DB) Period: Macitentan 10 mg | DB Period: Placebo | Open-Label (OL) Period: Macitentan 10 mg | OL Extension Period: Macitentan 10 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/43 (20.9%) | 6/42 (14.3%) | 18/80 (22.5%) | 11/33 (33.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/43 (0%) | 0/42 (0%) | 2/80 (2.5%) | 1/33 (3%) | ||||
| Iron Deficiency Anaemia | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Thrombocytopenia | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Cardiac disorders | ||||||||
| Atrial Fibrillation | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Left Ventricular Failure | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Right Ventricular Failure | 2/43 (4.7%) | 1/42 (2.4%) | 2/80 (2.5%) | 2/33 (6.1%) | ||||
| Ear and labyrinth disorders | ||||||||
| Tinnitus | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal Pain | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Ascites | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Duodenal Vascular Ectasia | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Gastrointestinal Angiodysplasia | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Gastrointestinal Haemorrhage | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Ileus | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Intestinal Obstruction | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Melaena | 0/43 (0%) | 0/42 (0%) | 2/80 (2.5%) | 1/33 (3%) | ||||
| Portal Hypertensive Gastropathy | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| General disorders | ||||||||
| Death | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Localised Oedema | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Oedema Peripheral | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatic Failure | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Immune system disorders | ||||||||
| Hypersensitivity | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Escherichia Pyelonephritis | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Gastroenteritis | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Lung Infection | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Pneumonia | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Staphylococcal Infection | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Urosepsis | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Localised Infection | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Fall | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Humerus Fracture | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Subdural Haematoma | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Vascular Procedure Complication | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Investigations | ||||||||
| Liver Function Test Increased | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Troponin I Increased | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Diabetes Mellitus | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Fluid Overload | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Intervertebral Disc Protrusion | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Osteitis | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Hepatocellular Carcinoma | 1/43 (2.3%) | 2/42 (4.8%) | 0/80 (0%) | 0/33 (0%) | ||||
| Malignant Ascites | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Rectal Adenocarcinoma | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Testis Cancer | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Nervous system disorders | ||||||||
| Haemorrhagic Stroke | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Hepatic Encephalopathy | 1/43 (2.3%) | 0/42 (0%) | 2/80 (2.5%) | 2/33 (6.1%) | ||||
| Presyncope | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Syncope | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute Kidney Injury | 1/43 (2.3%) | 1/42 (2.4%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Chronic Kidney Disease | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Priapism | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute Pulmonary Oedema | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Alveolitis | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Asthma | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Haemoptysis | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Pulmonary Arterial Hypertension | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Pulmonary Toxicity | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Surgical and medical procedures | ||||||||
| Aneurysm Repair | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Double-Blind (DB) Period: Macitentan 10 mg | DB Period: Placebo | Open-Label (OL) Period: Macitentan 10 mg | OL Extension Period: Macitentan 10 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 34/43 (79.1%) | 32/42 (76.2%) | 62/80 (77.5%) | 30/33 (90.9%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 2/43 (4.7%) | 0/42 (0%) | 9/80 (11.3%) | 5/33 (15.2%) | ||||
| Increased Tendency to Bruise | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Iron Deficiency Anaemia | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Leukopenia | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Neutropenia | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Leukocytosis | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Pancytopenia | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Cardiac disorders | ||||||||
| Arrhythmia | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Atrial Fibrillation | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Bradycardia | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Cyanosis | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Palpitations | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 2/33 (6.1%) | ||||
| Pericarditis | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Right Ventricular Failure | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Tachycardia | 2/43 (4.7%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear Pain | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Tinnitus | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Vertigo | 0/43 (0%) | 1/42 (2.4%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Eye disorders | ||||||||
| Cataract | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Conjunctival Hyperaemia | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Diabetic Retinopathy | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Diplopia | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Dry Eye | 0/43 (0%) | 1/42 (2.4%) | 2/80 (2.5%) | 0/33 (0%) | ||||
| Eye Irritation | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Eye Oedema | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Eye Pruritus | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Eye Swelling | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Meibomian Gland Dysfunction | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Vision Blurred | 1/43 (2.3%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Conjunctival Haemorrhage | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Lacrimation Decreased | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal Pain | 2/43 (4.7%) | 1/42 (2.4%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Abdominal Pain Upper | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Anal Polyp | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Ascites | 0/43 (0%) | 0/42 (0%) | 2/80 (2.5%) | 0/33 (0%) | ||||
| Constipation | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Diarrhoea | 1/43 (2.3%) | 4/42 (9.5%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Dry Mouth | 1/43 (2.3%) | 2/42 (4.8%) | 0/80 (0%) | 0/33 (0%) | ||||
| Duodenal Polyp | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Gastritis | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Gastritis Erosive | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Gastrooesophageal Reflux Disease | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Gingival Bleeding | 0/43 (0%) | 1/42 (2.4%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Nausea | 1/43 (2.3%) | 2/42 (4.8%) | 3/80 (3.8%) | 0/33 (0%) | ||||
| Pancreatic Cyst | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Portal Hypertensive Gastropathy | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Rectal Haemorrhage | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Varices Oesophageal | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Vomiting | 1/43 (2.3%) | 0/42 (0%) | 2/80 (2.5%) | 1/33 (3%) | ||||
| Abdominal Discomfort | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Abdominal Distension | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Glossodynia | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| General disorders | ||||||||
| Asthenia | 0/43 (0%) | 1/42 (2.4%) | 4/80 (5%) | 3/33 (9.1%) | ||||
| Chest Pain | 0/43 (0%) | 1/42 (2.4%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Face Oedema | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Fatigue | 0/43 (0%) | 1/42 (2.4%) | 2/80 (2.5%) | 0/33 (0%) | ||||
| Generalised Oedema | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Influenza Like Illness | 0/43 (0%) | 0/42 (0%) | 3/80 (3.8%) | 2/33 (6.1%) | ||||
| Localised Oedema | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Malaise | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Non-Cardiac Chest Pain | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Oedema Peripheral | 10/43 (23.3%) | 5/42 (11.9%) | 13/80 (16.3%) | 5/33 (15.2%) | ||||
| Pain | 0/43 (0%) | 1/42 (2.4%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Peripheral Swelling | 2/43 (4.7%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Swelling | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Temperature Intolerance | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Biliary Colic | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Cholelithiasis | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Hepatic Mass | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Jaundice | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Portal Vein Thrombosis | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Infections and infestations | ||||||||
| Bacterial Infection | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Bronchitis | 4/43 (9.3%) | 0/42 (0%) | 3/80 (3.8%) | 13/33 (39.4%) | ||||
| Candida Infection | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Conjunctivitis | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Fungal Infection | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Furuncle | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Gastroenteritis | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Gastrointestinal Infection | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Herpes Virus Infection | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Herpes Zoster | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Influenza | 0/43 (0%) | 1/42 (2.4%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Laryngitis | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Lower Respiratory Tract Infection | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Nasopharyngitis | 2/43 (4.7%) | 2/42 (4.8%) | 3/80 (3.8%) | 2/33 (6.1%) | ||||
| Periodontitis | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Rhinitis | 2/43 (4.7%) | 0/42 (0%) | 4/80 (5%) | 7/33 (21.2%) | ||||
| Sinusitis | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 2/33 (6.1%) | ||||
| Sinusitis Fungal | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Tonsillitis | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Tooth Abscess | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Upper Respiratory Tract Infection | 0/43 (0%) | 1/42 (2.4%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Urinary Tract Infection | 2/43 (4.7%) | 0/42 (0%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Groin Abscess | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Onychomycosis | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Pharyngitis | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Anaemia Postoperative | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Contusion | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Eye Contusion | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Fall | 2/43 (4.7%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Foot Fracture | 1/43 (2.3%) | 2/42 (4.8%) | 0/80 (0%) | 1/33 (3%) | ||||
| Head Injury | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Limb Injury | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Tooth Fracture | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Joint Dislocation | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Procedural Pain | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Investigations | ||||||||
| Ammonia Increased | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Aspartate Aminotransferase Increased | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Blood Bilirubin Increased | 0/43 (0%) | 1/42 (2.4%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Blood Creatinine Increased | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Blood Glucose Increased | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Blood Potassium Decreased | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Blood Potassium Increased | 0/43 (0%) | 1/42 (2.4%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Blood Sodium Decreased | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Blood Uric Acid Increased | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Blood Urine Present | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Brain Natriuretic Peptide Increased | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Coronavirus Test Positive | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Haematocrit Decreased | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Haemoglobin Decreased | 3/43 (7%) | 0/42 (0%) | 3/80 (3.8%) | 0/33 (0%) | ||||
| Intestinal Transit Time Decreased | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Liver Function Test Abnormal | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Oxygen Saturation Decreased | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Platelet Count Decreased | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Urine Output Decreased | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Intestinal Transit Time Abnormal | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Venous Pressure Jugular Increased | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Weight Increased | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased Appetite | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Fluid Retention | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 1/33 (3%) | ||||
| Folate Deficiency | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Gout | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Hypoglycaemia | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Hypokalaemia | 2/43 (4.7%) | 6/42 (14.3%) | 2/80 (2.5%) | 2/33 (6.1%) | ||||
| Hypomagnesaemia | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Iron Deficiency | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Magnesium Deficiency | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Vitamin D Deficiency | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/43 (2.3%) | 1/42 (2.4%) | 2/80 (2.5%) | 1/33 (3%) | ||||
| Back Pain | 2/43 (4.7%) | 1/42 (2.4%) | 1/80 (1.3%) | 2/33 (6.1%) | ||||
| Bone Pain | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Dupuytren's Contracture | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Joint Swelling | 1/43 (2.3%) | 1/42 (2.4%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Muscle Spasms | 0/43 (0%) | 5/42 (11.9%) | 3/80 (3.8%) | 0/33 (0%) | ||||
| Musculoskeletal Chest Pain | 0/43 (0%) | 0/42 (0%) | 2/80 (2.5%) | 0/33 (0%) | ||||
| Musculoskeletal Stiffness | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Myalgia | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Neck Pain | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Osteoarthritis | 0/43 (0%) | 0/42 (0%) | 2/80 (2.5%) | 1/33 (3%) | ||||
| Pain in Extremity | 2/43 (4.7%) | 3/42 (7.1%) | 6/80 (7.5%) | 1/33 (3%) | ||||
| Pain in Jaw | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Sebaceous Adenoma | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Nervous system disorders | ||||||||
| Balance Disorder | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Dizziness | 2/43 (4.7%) | 2/42 (4.8%) | 5/80 (6.3%) | 1/33 (3%) | ||||
| Headache | 7/43 (16.3%) | 7/42 (16.7%) | 10/80 (12.5%) | 1/33 (3%) | ||||
| Hepatic Encephalopathy | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Hypoaesthesia | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Intracranial Aneurysm | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Lethargy | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Neuralgia | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Presyncope | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Restless Legs Syndrome | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Sciatica | 1/43 (2.3%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Syncope | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Tremor | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Psychiatric disorders | ||||||||
| Alcohol Abuse | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Depression | 1/43 (2.3%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Insomnia | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 5/33 (15.2%) | ||||
| Sleep Disorder | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute Kidney Injury | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Oliguria | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Renal Failure | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Chromaturia | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Breast Mass | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Uterine Haemorrhage | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Gynaecomastia | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Bendopnoea | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Chronic Obstructive Pulmonary Disease | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Cough | 0/43 (0%) | 3/42 (7.1%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Dry Throat | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Dyspnoea | 1/43 (2.3%) | 2/42 (4.8%) | 3/80 (3.8%) | 3/33 (9.1%) | ||||
| Dyspnoea Exertional | 0/43 (0%) | 0/42 (0%) | 3/80 (3.8%) | 0/33 (0%) | ||||
| Epistaxis | 0/43 (0%) | 0/42 (0%) | 2/80 (2.5%) | 1/33 (3%) | ||||
| Hypoxia | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 2/33 (6.1%) | ||||
| Nasal Dryness | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Nasal Obstruction | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Oropharyngeal Pain | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 3/33 (9.1%) | ||||
| Portopulmonary Hypertension | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Pulmonary Arterial Hypertension | 1/43 (2.3%) | 1/42 (2.4%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Sinus Congestion | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Sleep Apnoea Syndrome | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Sneezing | 1/43 (2.3%) | 0/42 (0%) | 0/80 (0%) | 0/33 (0%) | ||||
| Haemoptysis | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Nasal Congestion | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Throat Irritation | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Blister | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Dermal Cyst | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Erythema | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Hyperkeratosis | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Pruritus | 0/43 (0%) | 1/42 (2.4%) | 3/80 (3.8%) | 0/33 (0%) | ||||
| Psoriasis | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Rash | 1/43 (2.3%) | 0/42 (0%) | 2/80 (2.5%) | 0/33 (0%) | ||||
| Umbilical Haemorrhage | 0/43 (0%) | 0/42 (0%) | 1/80 (1.3%) | 0/33 (0%) | ||||
| Vitiligo | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Hyperhidrosis | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Social circumstances | ||||||||
| Alcohol Use | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Surgical and medical procedures | ||||||||
| Inguinal Hernia Repair | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Oesophageal Variceal Ligation | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 1/33 (3%) | ||||
| Injection | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Skin Neoplasm Excision | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Vascular disorders | ||||||||
| Flushing | 1/43 (2.3%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
| Haematoma | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Hypotension | 2/43 (4.7%) | 0/42 (0%) | 3/80 (3.8%) | 0/33 (0%) | ||||
| Peripheral Venous Disease | 0/43 (0%) | 0/42 (0%) | 0/80 (0%) | 1/33 (3%) | ||||
| Orthostatic Hypotension | 0/43 (0%) | 1/42 (2.4%) | 0/80 (0%) | 0/33 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Any study-related publication written independently by investigators must be submitted to Actelion for review at least 30 days prior to submission for publication or presentation. Upon review, Actelion may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights.
Results Point of Contact
| Name/Title | Clinical Trial Disclosure Desk |
|---|---|
| Organization | Actelion Pharmaceuticals Ltd. |
| Phone | +41 61 565 6565 |
| clinical-trials-disclosure@its.jnj.com |
Responsible Party:
Actelion
ClinicalTrials.gov Identifier:
NCT02382016
Other Study ID Numbers:
- AC-055-404
First Posted:
Mar 6, 2015
Last Update Posted:
Nov 5, 2019
Last Verified:
Oct 1, 2019