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company decision
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The DUAL-2 study is designed as a multicenter, double-blind two-period study with an initial fixed 16-week Period 1, followed by a Period 2 of variable duration. All patients completing Period 1 continue on their original randomized treatment into Period 2, until the last randomized patient has completed Period 1.
Patients are randomized in a 1:1:1 ratio (macitentan 3mg: macitentan 10mg: placebo).
The primary objective is to demonstrate the effect of macitentan on the reduction of the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcers (DU).
Other objectives include:
Recurrent digital ulcers (DU) are a manifestation of vascular disease in patients with systemic sclerosis (SSc), are an important source of morbidity and lead to impaired function in these patients. In this study, we are investigating whether treatment with the endothelin receptor antagonist, macitentan, decreases the development of new digital ulcers in patients with SSc. Macitentan is a highly potent, tissue-targeting dual endothelin receptor antagonist. Through complete blockade of endothelin action, macitentan is expected to protect tissue from the damaging effect of elevated endothelin. This therapy is not approved for the treatment of systemic sclerosis, but the use of an ERA is an attractive approach in combating the structural vascular damage observed in SSc leading to complications such as DUs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Macitentan 3 mg | Active Comparator | Oral macitentan 3 mg, once daily |
|
| Macitentan 10 mg | Active Comparator | Oral macitentan 10 mg, once daily |
|
| Placebo | Placebo Comparator | Oral placebo, once daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Macitentan 3 mg | Drug | Macitentan 3-mg tablet once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence Rate of New Digital Ulcers (DUs) up to Week 16 | 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. | Baseline to Week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Without a New DU up to Week 16 | 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. |
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Inclusion Criteria :
Exclusion Criteria :
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27163986 | Result | Khanna D, Denton CP, Merkel PA, Krieg T, Le Brun FO, Marr A, Papadakis K, Pope J, Matucci-Cerinic M, Furst DE; DUAL-1 Investigators; DUAL-2 Investigators. Effect of Macitentan on the Development of New Ischemic Digital Ulcers in Patients With Systemic Sclerosis: DUAL-1 and DUAL-2 Randomized Clinical Trials. JAMA. 2016 May 10;315(18):1975-88. doi: 10.1001/jama.2016.5258. |
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A screening visit was performed between Day -14 and Day -1 of the study. Of the 324 patients screened for the study, 59 were screen failures.
Conducted at 73 centers in 20 countries.The first patient randomized was 9 Feb 2012 and last patient, last visit was 6 Feb 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | Macitentan 3mg | Patients received macitentan once daily at a dose of 3 mg. |
| FG001 | Macitentan 10mg | Patients received macitentan once daily at a dose of 10 mg. |
| FG002 | Placebo | Patients received placebo once daily. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1: Baseline to Week 16 |
| |||||||||||||
| Period 2: Week 16 to End of Study |
|
Full analysis set
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| ID | Title | Description |
|---|---|---|
| BG000 | Macitentan 3mg | Patients received macitentan once daily at a dose of 3 mg. |
| BG001 | Macitentan 10mg | Patients received macitentan once daily at a dose of 10 mg. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Incidence Rate of New Digital Ulcers (DUs) up to Week 16 | 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. | Full analysis set | Posted | Number | new DUs/16 weeks | Baseline to Week 16 |
|
Adverse events occurring during treatment period, up to 95 weeks and up to 30 days after treatment discontinuation
Safety set - all treated patients
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Macitentan 3mg | Patients received macitentan once daily at a dose of 3 mg. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| INFECTED SKIN ULCER | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| HEADACHE | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Angelina Marr | Actelion Pharmaceuticals Ltd | +41 61 565 63 69 | angelina.marr@actelion.com |
| ID | Term |
|---|---|
| C000721267 | digital ulcers |
| D012595 | Scleroderma, Systemic |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| C533860 | macitentan |
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| Macitentan 10 mg | Drug | Macitentan 10-mg tablet once daily |
|
|
| Placebo | Drug | Placebo tablet matching macitentan tablet, once daily |
|
| Baseline to Week 16 |
| Percentage of Participants With at Least One DU Complication | 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. | Up to 95 weeks |
| Change in Hand Functionality Health Assessment Questionnaire - Disability Index (HAQ-DI) Hand Component From Baseline to Week 16 | 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). | Baseline to Week 16 |
| Health Assessment Questionnaire - Disability Index (HAQ-DI) Overall Score From Baseline to Week 16 | 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). | Baseline to Week 16 |
| Change in Hand Functionality - Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) Score From Baseline to Week 16 | 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) | Baseline to Week 16 |
| NOT COMPLETED |
|
| BG002 | Placebo | Patients received placebo once daily. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Macitentan 3mg |
Patients received macitentan once daily at a dose of 3 mg. |
| OG001 | Macitentan 10mg | Patients received macitentan once daily at a dose of 10 mg. |
| OG002 | Placebo | Patients received placebo once daily. |
|
|
|
| Secondary | Percentage of Participants Without a New DU up to Week 16 | 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. | Modified intention to treat set. Ten patients were excluded from the modified intent to treat set due to protocol violations. | Posted | Number | Percentage of participants | Baseline to Week 16 |
|
|
|
|
| Secondary | Percentage of Participants With at Least One DU Complication | 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. | Modified intention to treat set. Ten patients were excluded from the modified intent to treat set due to protocol violations. | Posted | Number | Percentage of participants | Up to 95 weeks |
|
|
|
|
| Secondary | Change in Hand Functionality Health Assessment Questionnaire - Disability Index (HAQ-DI) Hand Component From Baseline to Week 16 | 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). | Modified intention to treat set. Ten patients were excluded from the modified intent to treat set due to protocol violations. | Posted | Mean | Standard Deviation | Units on a scale | Baseline to Week 16 |
|
|
|
|
| Secondary | Health Assessment Questionnaire - Disability Index (HAQ-DI) Overall Score From Baseline to Week 16 | 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). | Modified intention to treat set. Ten patients were excluded from the modified intent to treat set due to protocol violations. | Posted | Mean | Standard Deviation | Units on a scale | Baseline to Week 16 |
|
|
|
|
| Secondary | Change in Hand Functionality - Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) Score From Baseline to Week 16 | 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) | Modified intention to treat set. Ten patients were excluded from the modified intent to treat set due to protocol violations. | Posted | Mean | Standard Deviation | Units on a scale | Baseline to Week 16 |
|
|
|
|
| 10 |
| 88 |
| 73 |
| 88 |
| EG001 | Macitentan 10mg | Patients received macitentan once daily at a dose of 10 mg. | 21 | 87 | 73 | 87 |
| EG002 | Placebo | Patients received placebo once daily. | 13 | 89 | 70 | 89 |
| PNEUMONIA | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| BRONCHITIS | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| ENTEROCOLITIS INFECTIOUS | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| GANGRENE | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| LOWER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| PERITONITIS | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| SEPSIS | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| STAPHYLOCOCCAL INFECTION | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| OSTEOMYELITIS | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| CELLULITIS | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| GASTROENTERITIS | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| PARONYCHIA | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| SMALL INTESTINAL OBSTRUCTION | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| SUBILEUS | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| ENTERITIS | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| OESOPHAGEAL ULCER | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| CARDIAC FAILURE | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| PERICARDITIS | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| RIGHT VENTRICULAR FAILURE | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| AORTIC VALVE STENOSIS | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| ARRHYTHMIA | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| ACUTE MYOCARDIAL INFARCTION | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| ANGINA PECTORIS | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| DEBRIDEMENT | Surgical and medical procedures | MedDRA 16.0 | Systematic Assessment |
|
| FINGER AMPUTATION | Surgical and medical procedures | MedDRA 16.0 | Systematic Assessment |
|
| IMMUNOSUPPRESSANT DRUG THERAPY | Surgical and medical procedures | MedDRA 16.0 | Systematic Assessment |
|
| PERIPHERAL ARTERY ANGIOPLASTY | Surgical and medical procedures | MedDRA 16.0 | Systematic Assessment |
|
| SYMPATHECTOMY | Surgical and medical procedures | MedDRA 16.0 | Systematic Assessment |
|
| DRUG THERAPY | Surgical and medical procedures | MedDRA 16.0 | Systematic Assessment |
|
| PELVIC FRACTURE | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| SPINAL CORD INJURY | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| CONCUSSION | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| FEMUR FRACTURE | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| POST PROCEDURAL HAEMORRHAGE | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| THORACIC VERTEBRAL FRACTURE | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| SYSTEMIC SCLEROSIS | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| MYOPATHY | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| RHEUMATOID ARTHRITIS | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| SCLERODERMA RENAL CRISIS | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| NEPHROPATHY TOXIC | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| RENAL FAILURE ACUTE | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| GLOMERULONEPHRITIS RAPIDLY PROGRESSIVE | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| NEPHROLITHIASIS | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| SKIN ULCER | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| SKIN NECROSIS | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| HYPERTENSION | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
|
| RAYNAUD'S PHENOMENON | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
|
| PERIPHERAL ISCHAEMIA | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
|
| DRUG-INDUCED LIVER INJURY | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
|
| ISCHAEMIC HEPATITIS | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
|
| DEHYDRATION | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| VESTIBULAR DISORDER | Ear and labyrinth disorders | MedDRA 16.0 | Systematic Assessment |
|
| GENERAL PHYSICAL HEALTH DETERIORATION | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| ISCHAEMIC ULCER | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| GASTRIC CANCER | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
|
| PULMONARY FIBROSIS | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| PULMONARY HYPERTENSION | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| PULMONARY ALVEOLAR HAEMORRHAGE | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| OEDEMA PERIPHERAL | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| NASOPHARYNGITIS | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
|
| INFECTED SKIN ULCER | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| SKIN ULCER | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| DIZZINESS | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| FATIGUE | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| INFLUENZA | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| DYSPEPSIA | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| CONSTIPATION | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| DERMATITIS | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| BURSITIS | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| OROPHARYNGEAL PAIN | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| PHARYNGITIS | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
Not provided
| Odds Ratio (OR) |
| 0.789 |
| 2-Sided |
| 95 |
| 0.420 |
| 1.484 |
| Superiority or Other (legacy) |
| Odds Ratio (OR) |
| 1.048 |
| 2-Sided |
| 95 |
| 0.485 |
| 2.264 |
| Superiority or Other (legacy) |
|
| Mean Difference (Net) |
| -0.1 |
| 2-Sided |
| 95 |
| -0.3 |
| 0.0 |
| Superiority or Other (legacy) |
|
| Mean Difference (Net) |
| -0.1 |
| 2-Sided |
| 95 |
| -0.2 |
| 0.1 |
| Superiority or Other (legacy) |
|
| Mean Difference (Net) |
| -0.2 |
| 2-Sided |
| 95 |
| -0.4 |
| 0.1 |
| Superiority or Other (legacy) |