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Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients (DUAL-1)

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: NCT01474109
Recruitment Status : Completed
First Posted : November 18, 2011
Results First Posted : January 6, 2015
Last Update Posted : January 6, 2015
Sponsor:
Information provided by (Responsible Party):
Actelion

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Systemic Sclerosis
Ulcers
Interventions Drug: macitentan 3mg
Drug: macitentan 10mg
Drug: placebo
Enrollment 289
Recruitment Details Conducted at 70 centers in 17 countries. First patient randomized was 11 January 2012 and last patient, last visit was 29 November 2013.
Pre-assignment Details A screening visit was performed between Day −14 and Day −1 of the study. Of the 327 patients screened for the study, 38 were screen failures.
Arm/Group Title Macitentan 3mg Macitentan 10mg Placebo
Hide Arm/Group Description

macitentan 3mg tablet once daily

macitentan 3mg: macitentan 3mg tablet once daily

macitentan 10mg tablet once daily

macitentan 10mg: macitentan 10mg tablet once daily

matching placebo once daily

placebo: matching placebo once daily

Period Title: Period 1: Baseline to Week 16
Started 95 97 97
Completed 88 91 95
Not Completed 7 6 2
Period Title: Period 2: Week 16 to End of Study
Started 88 91 95
Completed 70 73 83
Not Completed 18 18 12
Arm/Group Title Macitentan 3mg Macitentan 10mg Placebo Total
Hide Arm/Group Description

macitentan 3mg tablet once daily

macitentan 3mg: macitentan 3mg tablet once daily

macitentan 10mg tablet once daily

macitentan 10mg: macitentan 10mg tablet once daily

matching placebo once daily

placebo: matching placebo once daily

Total of all reporting groups
Overall Number of Baseline Participants 95 97 97 289
Hide Baseline Analysis Population Description
Full analysis set
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 95 participants 97 participants 97 participants 289 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
77
  81.1%
84
  86.6%
84
  86.6%
245
  84.8%
>=65 years
18
  18.9%
13
  13.4%
13
  13.4%
44
  15.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 95 participants 97 participants 97 participants 289 participants
51.4  (14.44) 51.6  (11.10) 50.6  (12.12) 51.2  (12.58)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 95 participants 97 participants 97 participants 289 participants
Female
84
  88.4%
81
  83.5%
83
  85.6%
248
  85.8%
Male
11
  11.6%
16
  16.5%
14
  14.4%
41
  14.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 95 participants 97 participants 97 participants 289 participants
White 86 82 88 256
Black or African American 0 3 1 4
Asian 5 6 4 15
Hispanic 3 4 3 10
Other 1 2 1 4
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 95 participants 97 participants 97 participants 289 participants
Australia 10 9 9 28
Belarus 3 3 5 11
Bulgaria 13 16 17 46
Canada 1 3 2 6
Chile 6 7 4 17
Colombia 0 2 1 3
Croatia 3 1 6 10
Czech Republic 6 3 5 14
France 0 0 1 1
Germany 9 7 11 27
Hungary 4 7 3 14
India 4 5 4 13
Italy 3 3 2 8
Poland 5 3 3 11
Russian Federation 6 7 8 21
Ukraine 10 5 7 22
United States 12 16 9 37
1.Primary Outcome
Title Incidence Rate of New Digital Ulcers (DUs) up to Week 16
Hide Description DUs were assessed at each visit starting with the screening visit. Only DUs from the proximal interphalangeal joint (PIP) distally (both on the dorsal and volar surface of the hand, including the digital tip) were recorded. The location of each DU was noted. At each subsequent visit the location of each new DU was noted. DUs that occurred and healed between visits and were reported by patients were not recorded as new DUs. The evaluation was performed by an experienced physician or a trained rater with expertise in the assessment of DUs in systemic sclerosis (SSc). For a given patient, DUs were assessed by the same rater at each visit, whenever possible. Any DU that developed over a previously healed ulcer was recorded as a new DU. Incidence rate is adjusted for 16 weeks of observation, hence is calculated as the number of new DUs/total number of observation days.
Time Frame Baseline to week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Macitentan 3mg Macitentan 10mg Placebo
Hide Arm/Group Description:

macitentan 3mg tablet once daily

macitentan 3mg: macitentan 3mg tablet once daily

macitentan 10mg tablet once daily

macitentan 10mg: macitentan 10mg tablet once daily

matching placebo once daily

placebo: matching placebo once daily

Overall Number of Participants Analyzed 95 97 97
Measure Type: Number
Unit of Measure: number of new DUs/observation days
0.9082 0.9567 0.8115
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Macitentan 3mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.706
Comments [Not Specified]
Method negative binomial-2 regression (NB-2)
Comments [Not Specified]
Method of Estimation Estimation Parameter NB-2 estimate of new DUs per patient
Estimated Value 1.103
Confidence Interval (2-Sided) 95%
0.663 to 1.834
Estimation Comments The estimated value corresponds to the treatment effect i.e. the ratio between the estimated number of new DUs in Macitentan 3 mg and in Placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Macitentan 10mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.360
Comments [Not Specified]
Method negative binomial-2 regression (NB-2)
Comments [Not Specified]
Method of Estimation Estimation Parameter NB-2 estimate of new DUs per patient
Estimated Value 1.268
Confidence Interval (2-Sided) 95%
0.763 to 2.106
Estimation Comments The estimated value corresponds to the treatment effect i.e. the ratio between the estimated number of new DUs in Macitentan 10 mg and in Placebo
2.Secondary Outcome
Title Percentage of Participants Without a New DU Up To Week 16
Hide Description DUs were assessed at each visit starting with the screening visit. Only DUs from the proximal interphalangeal joint (PIP) distally (both on the dorsal and volar surface of the hand, including the digital tip) were recorded. The location of each DU was noted. At each subsequent visit the location of each new DU was noted. DUs that occurred and healed between visits and were reported by patients were not recorded as new DUs. The evaluation was performed by an experienced physician or a trained rater with expertise in the assessment of DUs in systemic sclerosis (SSc). For a given patient, DUs were assessed by the same rater at each visit, whenever possible. Any DU that developed over a previously healed ulcer was recorded as a new DU. Numbers of patients with no new DU at Week 16 are imputed using the last observation carried forward method.
Time Frame Baseline to week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat set. Eleven patients were excluded from the modified intent-treat set due to protocol violations.
Arm/Group Title Macitentan 3mg Macitentan 10mg Placebo
Hide Arm/Group Description:

macitentan 3mg tablet once daily

macitentan 3mg: macitentan 3mg tablet once daily

macitentan 10mg tablet once daily

macitentan 10mg: macitentan 10mg tablet once daily

matching placebo once daily

placebo: matching placebo once daily

Overall Number of Participants Analyzed 92 92 94
Measure Type: Number
Unit of Measure: Percentage of participants
64.1 63.0 67.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Macitentan 3mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6670
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.875
Confidence Interval (2-Sided) 95%
0.477 to 1.606
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Macitentan 10mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5518
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.832
Confidence Interval (2-Sided) 95%
0.454 to 1.524
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With at Least One DU Complication
Hide Description DU complications were defined as any one of the following, resulting from DU worsening: critical ischemic crisis necessitating hospitalization; gangrene, (auto)amputation; failure of conservative management; surgical and chemical sympathectomy, vascular reconstructions, or any unplanned surgery in the management of hand SSc manifestations; use of parenteral prostanoids; use of endothelin-receptor antagonists; class II, III, or IV narcotics or a > 50% increase in the existing dose compared with baseline; initiation of systemic antibiotics for the treatment of infection attributed to DUs.
Time Frame Up to approximately 90 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat set. Eleven patients were excluded from the modified intent-treat set due to protocol violations.
Arm/Group Title Macitentan 3mg Macitentan 10mg Placebo
Hide Arm/Group Description:

macitentan 3mg tablet once daily

macitentan 3mg: macitentan 3mg tablet once daily

macitentan 10mg tablet once daily

macitentan 10mg: macitentan 10mg tablet once daily

matching placebo once daily

placebo: matching placebo once daily

Overall Number of Participants Analyzed 92 92 94
Measure Type: Number
Unit of Measure: percentage of participants
14.1 19.6 19.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Macitentan 3mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3625
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.696
Confidence Interval (2-Sided) 95%
0.319 to 1.518
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Macitentan 10mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9362
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.030
Confidence Interval (2-Sided) 95%
0.498 to 2.133
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change in Hand Functionality Health Assessment Questionnaire - Disability Index (HAQ-DI) Hand Component From Baseline to Week 16
Hide Description HAQ-DI assesses functional ability regarding fine movements of the upper extremities, locomotor activities in the lower extremities, and movements of the upper and lower limbs. Responses were extracted from the Scleroderma Health Assessment Questionnaire covering 8 domains of functional disability (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other daily activities). A mean score ranging from 0-3 was calculated for each domain, and a composite score by dividing the summed domain scores by the number of domains. The composite score was interpreted as 0 (no impairment in function) to 3 (maximal impairment of function). Hand functionality was assessed using a composite of 4 domains (dressing and grooming, grip, hygiene, and eating).
Time Frame Baseline to week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intention-to-treat set. Eleven patients were excluded from the modified intent-treat set due to protocol violations.
Arm/Group Title Macitentan 3mg Macitentan 10mg Placebo
Hide Arm/Group Description:

macitentan 3mg tablet once daily

macitentan 3mg: macitentan 3mg tablet once daily

macitentan 10mg tablet once daily

macitentan 10mg: macitentan 10mg tablet once daily

matching placebo once daily

placebo: matching placebo once daily

Overall Number of Participants Analyzed 92 92 94
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 1.3  (0.73) 1.4  (0.70) 1.3  (0.68)
Week 16 1.2  (0.79) 1.2  (0.66) 1.2  (0.73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Macitentan 3mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.863
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.1 to 0.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Macitentan 10mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.649
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.2 to 0.1
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Health Assessment Questionnaire - Disability Index (HAQ-DI) Overall Score From Baseline to Week 16
Hide Description HAQ-DI assesses functional ability regarding fine movements of the upper extremities, locomotor activities in the lower extremities, and movements of the upper and lower limbs. Responses were extracted from the Scleroderma Health Assessment Questionnaire covering 8 domains of functional disability (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other daily activities). A mean score ranging from 0-3 was calculated for each domain, and a composite score by dividing the summed domain scores by the number of domains. The composite score was interpreted as 0 (no impairment in function) to 3 (maximal impairment of function).
Time Frame Baseline to week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intention-to-treat set. Eleven patients were excluded from the modified intent-treat set due to protocol violations.
Arm/Group Title Macitentan 3mg Macitentan 10mg Placebo
Hide Arm/Group Description:

macitentan 3mg tablet once daily

macitentan 3mg: macitentan 3mg tablet once daily

macitentan 10mg tablet once daily

macitentan 10mg: macitentan 10mg tablet once daily

matching placebo once daily

placebo: matching placebo once daily

Overall Number of Participants Analyzed 92 92 94
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 1.1  (0.71) 1.2  (0.66) 1.1  (0.62)
Week 16 1.1  (0.73) 1.1  (0.64) 1.1  (0.67)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Macitentan 3mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.456
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.2 to 0.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Macitentan 10mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.440
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.2 to 0.1
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change in Hand Functionality - Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) Score From Baseline to Week 16
Hide Description Patients were asked to answer 24 questions on the use of the hand(s) affected by DUs over the past 7 days on a 6-point scale from 0 (yes without difficulty) to 5 (impossible). The HDISS-DU score is the arithmetic mean of the valid non-missing items. The scores are interpreted as 1 (better ability in completing activities) to 6 (worst ability in completing activities)
Time Frame Baseline to week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intention-to-treat set. Eleven patients were excluded from the modified intent-treat set due to protocol violations.
Arm/Group Title Macitentan 3mg Macitentan 10mg Placebo
Hide Arm/Group Description:

macitentan 3mg tablet once daily

macitentan 3mg: macitentan 3mg tablet once daily

macitentan 10mg tablet once daily

macitentan 10mg: macitentan 10mg tablet once daily

matching placebo once daily

placebo: matching placebo once daily

Overall Number of Participants Analyzed 92 92 94
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 3.0  (1.15) 3.0  (1.09) 3.0  (1.09)
Week 16 2.7  (1.14) 2.6  (0.99) 2.7  (1.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Macitentan 3mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.464
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Macitentan 10mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.342
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.1
Estimation Comments [Not Specified]
Time Frame From start of study treatment up to 30 days after treatment discontinuation, up to approximately 90 weeks
Adverse Event Reporting Description Safety analysis set. One patient was excluded in the safety analysis set as they did not receive study drug after randomisation.
 
Arm/Group Title Macitentan 3mg Macitentan 10mg Placebo
Hide Arm/Group Description

macitentan 3mg tablet once daily

macitentan 3mg: macitentan 3mg tablet once daily

macitentan 10mg tablet once daily

macitentan 10mg: macitentan 10mg tablet once daily

matching placebo once daily

placebo: matching placebo once daily

All-Cause Mortality
Macitentan 3mg Macitentan 10mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Macitentan 3mg Macitentan 10mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/94 (18.09%)   14/97 (14.43%)   13/97 (13.40%) 
Blood and lymphatic system disorders       
ANAEMIA  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
Cardiac disorders       
ACUTE CORONARY SYNDROME  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
CARDIAC ARREST  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
PLEUROPERICARDITIS  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
VENTRICULAR EXTRASYSTOLES  1  2/94 (2.13%)  0/97 (0.00%)  0/97 (0.00%) 
ANGINA PECTORIS  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
ANGINA UNSTABLE  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
ATRIAL FIBRILLATION  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
ATRIAL FLUTTER  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
MYOCARDIAL FIBROSIS  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
MYOCARDIAL ISCHAEMIA  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
PERICARDIAL EFFUSION  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
PERICARDITIS  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
Gastrointestinal disorders       
ABDOMINAL DISTENSION  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
GASTRITIS  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
General disorders       
OEDEMA PERIPHERAL  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
CHEST PAIN  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
FATIGUE  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
PYREXIA  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
Hepatobiliary disorders       
CHOLECYSTITIS ACUTE  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
CHOLELITHIASIS  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
Infections and infestations       
INFECTED SKIN ULCER  1  0/94 (0.00%)  3/97 (3.09%)  1/97 (1.03%) 
PNEUMONIA  1  2/94 (2.13%)  1/97 (1.03%)  0/97 (0.00%) 
BACTERIAL SEPSIS  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
CLOSTRIDIUM DIFFICILE COLITIS  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
CLOSTRIDIUM DIFFICILE INFECTION  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
SEPSIS  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
GANGRENE  1  3/94 (3.19%)  0/97 (0.00%)  0/97 (0.00%) 
BRONCHOPNEUMONIA  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
CELLULITIS  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
ERYSIPELAS  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
PNEUMOCOCCAL SEPSIS  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
SINUSITIS  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
OESOPHAGEAL CANDIDIASIS  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
Injury, poisoning and procedural complications       
FALL  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
POST PROCEDURAL HAEMORRHAGE  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
Metabolism and nutrition disorders       
DIABETES MELLITUS INADEQUATE CONTROL  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
FAILURE TO THRIVE  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
HYPOGLYCAEMIA  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
Musculoskeletal and connective tissue disorders       
INTERVERTEBRAL DISC PROTRUSION  1  1/94 (1.06%)  1/97 (1.03%)  0/97 (0.00%) 
LUMBAR SPINAL STENOSIS  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
PAIN IN EXTREMITY  1  0/94 (0.00%)  1/97 (1.03%)  1/97 (1.03%) 
SYSTEMIC SCLEROSIS  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
OSTEOARTHRITIS  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
OSTEONECROSIS  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
RHEUMATOID ARTHRITIS  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
SCLERODERMA  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
METASTATIC BRONCHIAL CARCINOMA  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
B-CELL LYMPHOMA  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
Nervous system disorders       
LOSS OF CONSCIOUSNESS  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
NEURALGIA  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
Psychiatric disorders       
CONFUSIONAL STATE  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
Renal and urinary disorders       
RENAL FAILURE  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
URINARY INCONTINENCE  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
NEPHROTIC SYNDROME  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
RENAL DISORDER  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
SCLERODERMA RENAL CRISIS  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
Reproductive system and breast disorders       
UTERINE PROLAPSE  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
PNEUMONIA ASPIRATION  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
HYDROTHORAX  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
PULMONARY CONGESTION  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
PULMONARY EMBOLISM  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
RESPIRATORY FAILURE  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
Skin and subcutaneous tissue disorders       
SKIN ULCER  1  3/94 (3.19%)  2/97 (2.06%)  3/97 (3.09%) 
LEUKOCYTOCLASTIC VASCULITIS  1  0/94 (0.00%)  1/97 (1.03%)  0/97 (0.00%) 
DRY GANGRENE  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
HYPERKERATOSIS  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
Surgical and medical procedures       
PROSTATIC OPERATION  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
Vascular disorders       
GRANULOMATOSIS WITH POLYANGIITIS  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
HYPERTENSION  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
HYPOTENSION  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
NECROSIS ISCHAEMIC  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
PERIPHERAL ISCHAEMIA  1  1/94 (1.06%)  0/97 (0.00%)  0/97 (0.00%) 
RAYNAUD'S PHENOMENON  1  1/94 (1.06%)  0/97 (0.00%)  1/97 (1.03%) 
EXTREMITY NECROSIS  1  0/94 (0.00%)  0/97 (0.00%)  1/97 (1.03%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Macitentan 3mg Macitentan 10mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   61/94 (64.89%)   73/97 (75.26%)   69/97 (71.13%) 
Blood and lymphatic system disorders       
ANAEMIA  1  4/94 (4.26%)  8/97 (8.25%)  7/97 (7.22%) 
Gastrointestinal disorders       
GASTROOESOPHAGEAL REFLUX DISEASE  1  0/94 (0.00%)  6/97 (6.19%)  5/97 (5.15%) 
DIARRHOEA  1  6/94 (6.38%)  5/97 (5.15%)  7/97 (7.22%) 
NAUSEA  1  5/94 (5.32%)  4/97 (4.12%)  6/97 (6.19%) 
General disorders       
OEDEMA PERIPHERAL  1  7/94 (7.45%)  12/97 (12.37%)  6/97 (6.19%) 
Infections and infestations       
INFECTED SKIN ULCER  1  7/94 (7.45%)  12/97 (12.37%)  11/97 (11.34%) 
UPPER RESPIRATORY TRACT INFECTION  1  3/94 (3.19%)  7/97 (7.22%)  4/97 (4.12%) 
BRONCHITIS  1  7/94 (7.45%)  1/97 (1.03%)  5/97 (5.15%) 
Investigations       
ALANINE AMINOTRANSFERASE INCREASED  1  2/94 (2.13%)  6/97 (6.19%)  1/97 (1.03%) 
ASPARTATE AMINOTRANSFERASE INCREASED  1  3/94 (3.19%)  5/97 (5.15%)  1/97 (1.03%) 
Musculoskeletal and connective tissue disorders       
BACK PAIN  1  3/94 (3.19%)  5/97 (5.15%)  3/97 (3.09%) 
ARTHRALGIA  1  6/94 (6.38%)  4/97 (4.12%)  7/97 (7.22%) 
PAIN IN EXTREMITY  1  4/94 (4.26%)  4/97 (4.12%)  6/97 (6.19%) 
Nervous system disorders       
HEADACHE  1  14/94 (14.89%)  19/97 (19.59%)  12/97 (12.37%) 
DIZZINESS  1  4/94 (4.26%)  5/97 (5.15%)  2/97 (2.06%) 
Skin and subcutaneous tissue disorders       
SKIN ULCER  1  6/94 (6.38%)  8/97 (8.25%)  9/97 (9.28%) 
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
Layout table for Results Point of Contact information
Name/Title: Angelina Marr
Organization: Actelion Pharmaceuticals Ltd
Phone: +41 61 565 63 69
EMail: angelina.marr@actelion.com
Layout table for additonal information
Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01474109    
Other Study ID Numbers: AC-055C301
First Submitted: October 31, 2011
First Posted: November 18, 2011
Results First Submitted: December 3, 2014
Results First Posted: January 6, 2015
Last Update Posted: January 6, 2015