Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The aim of the study is to collect long-term efficacy, tolerability and safety data of bosentan in Systemic Sclerosis (SSc) patients suffering from ischemic digital ulcers (DUs).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bosentan | Experimental | Bosentan 62.5 mg tablets b.i.d. for the first 4 weeks followed by bosentan 125 mg b.i.d. thereafter |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bosentan 62.5 mg | Drug | Bosentan 62.5-mg oral tablets twice daily (b.i.d.) for 4 weeks (initial dose) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Complete Healing of Each Baseline DU | Baseline to healing | |
| Time to Complete Healing of Each New DU | New DU occurence to healing | |
| Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Dressing | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | 80 weeks |
| Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Arising | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | 80 weeks |
| Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Eating | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events up to 24 Hours After Last Study Medication | Number of patients with at least one treatment-emergent adverse event. All adverse events that occurred after study drug initiation and up to 24 hours after study drug discontinuation were to be recorded. | 80 weeks |
| Adverse Events Leading to Permanent Discontinuation of the Study Medication |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Patients who completed RAPIDS-2 and who still had digital ulcers (DUs) or developed a new digital ulcer (DU) after the last follow-up visit were eligible. After release of the RAPIDS-2 results, patients who were prematurely discontinued from RAPIDS-2 for treatment failure or, if on placebo, for an adverse event and had DUs were also eligible.
Patients were enrolled at 33 centers in 7 countries (Canada, France, Germany, Italy, Switzerland, UK, and USA. The first patient enrolled and started treatment on 8 July 2004 and the last patient enrolled and started treatment on 20 October 2005.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Bosentan | Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Bosentan | Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Time to Complete Healing of Each Baseline DU | Complete healing of each baseline was not calculated due to the lack of effect on healing variables seen in the previous placebo-controlled study (RAPIDS 2). In consequence, the endpoint on time to complete healing of baseline DUs was not evaluated. | Posted | Baseline to healing |
|
|
80 weeks
Treatment-emergent adverse events
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 | Bosentan | Initial dose: bosentan 62.5 mg twice daily (b.i.d.) for the first 4 weeks. Target dose: bosentan 125 mg b.i.d. thereafter |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| PNEUMONIA | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| SKIN ULCER | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Andjela Kusic-Pajic, MD/Clinical Project Team Leader | Actelion Pharmaceuticals Ltd | +41 61 565 64 17 |
| ID | Term |
|---|---|
| C000721267 | digital ulcers |
| D012595 | Scleroderma, Systemic |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012871 | Skin Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077300 | Bosentan |
| ID | Term |
|---|---|
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Bosentan 125 mg | Drug | Bosentan 125-mg oral tablets administered b.i.d. (target dose) |
|
| 80 weeks |
| Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Walking | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | 80 weeks |
| Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Hygiene | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | 80 weeks |
| Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Reach | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | 80 weeks |
| Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Grip | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | 80 weeks |
| Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Activity | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | 80 weeks |
| Mean Changes From Baseline at Each 16 Week Interval up to Week 80 in Overall Hand Pain Related to Finger Ulcers | Overall hand pain related to finger ulcers was assessed by the patient using a Visual Analogue Scale. Patients were instructed to score their pain by marking on the continuous 10-cm scale, where 0 (left) was no pain and 100 (right) very severe pain, in response to the question, "How much pain have you had because of your finger ulcers in the past week?" The investigator measured the distance in millimeters between 0 and the patient mark with the ruler provided and recorded the distance. | 80 weeks |
| Mean Change From Baseline at Each 16 Week Interval up to Week 80 in the UK Systemic Sclerosis Functional Score (UKFS) | UKFS relates to upper and lower extremity function and muscle weakness. For each item, the patient indicated the responses that best described their current ability: "able to perform in a normal manner," "able to perform with alteration in style," "can only manage with difficulty," and "impossible to achieve." Each response was given an integer from 0 (able to perform in a normal manner) to 3 (impossible to achieve), and the sum of individual responses provided an overall score of 0 to 33. Missing values were replaced with the worst value the patient reported on the other items at that visit. | 80 weeks |
| Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits | The total number of new DUs per patient observed by the investigator at planned visits and new transient DUs recorded in the patient diary (a patient diary was used to record DUs that might appear and disappear between two planned visits) were assessed at each clinic visit | At planned visits up to week 80 |
Number of patients with an adverse event leading to permanent discontinuation of the study treatment |
| 80 weeks |
| Serious Adverse Events up to 28 Days After Last Study Medication | Number of patients with at least one treatment-emergent serious adverse event (TESAE) were reported. TESAEs are serious AEs that occurred after study drug initiation and up to 28 days after study drug discontinuation. More details on the SAEs are provided in the specific Adverse Events Section | 80 weeks |
| Lost to Follow-up |
|
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | Mean | Standard Deviation | score on a scale |
|
| Overall hand pain | Overall hand pain related to finger ulcers was assessed by the patient using a Visual Analogue Scale. Patients were instructed to score their pain by marking on the continuous 10-cm scale, where 0 (left) was no pain and 100 (right) very severe pain, in response to the question, "How much pain have you had because of your finger ulcers in the past week?" The investigator measured the distance in millimeters between 0 and the patient mark with the ruler provided and recorded the distance. | Mean | Standard Deviation | mm |
|
| United Kingdom Scleroderma Functional Score (UKFS) | UKFS relates to upper and lower extremity function and muscle weakness. For each item, the patient indicated the responses that best described their current ability: "able to perform in a normal manner," "able to perform with alteration in style," "can only manage with difficulty," and "impossible to achieve." Each response was given an integer from 0 (able to perform in a normal manner) to 3 (impossible to achieve), and the sum of individual responses provided an overall score of 0 to 33. Missing values were replaced with the worst value the patient reported on the other items at that visit. | Mean | Standard Deviation | score on a scale |
|
| Primary | Time to Complete Healing of Each New DU | Complete healing of each new DU was not calculated due to the lack of effect on healing variables seen in the previous placebo-controlled study (RAPIDS 2). In consequence, the endpoint on DU healing originally planned time to complete healing of new DUs was not evaluated. | Posted | New DU occurence to healing |
|
|
| Primary | Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Dressing | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively | Posted | Mean | Standard Deviation | scores on a scale | 80 weeks |
|
|
|
| Primary | Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Arising | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively | Posted | Mean | Standard Deviation | scores on a scale | 80 weeks |
|
|
|
| Primary | Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Eating | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively | Posted | Mean | Standard Deviation | scores on a scale | 80 weeks |
|
|
|
| Primary | Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Walking | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively | Posted | Mean | Standard Deviation | scores on a scale | 80 weeks |
|
|
|
| Primary | Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Hygiene | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively | Posted | Mean | Standard Deviation | scores on a scale | 80 weeks |
|
|
|
| Primary | Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Reach | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively | Posted | Mean | Standard Deviation | scores on a scale | 80 weeks |
|
|
|
| Primary | Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Grip | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively | Posted | Mean | Standard Deviation | scores on a scale | 80 weeks |
|
|
|
| Primary | Mean Change From Baseline at Each 16 Week Interval up to Week 80 in Scleroderma Health Assessment Questionnaire (SHAQ) Individual Domain Score: Activity | SHAQ evaluates physical disability. Patients were instructed to rate their capacity to perform activities of daily living within the previous 7 days by checking one of the following descriptors: "without any difficulty", "with some difficulty," "with much difficulty," or "unable to do," equivalent to scores of 0, 1, 2, and 3, respectively. Items were categorized into 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. | number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 99, 93, 85, 82, and 78, respectively | Posted | Mean | Standard Deviation | scores on a scale | 80 weeks |
|
|
|
| Primary | Mean Changes From Baseline at Each 16 Week Interval up to Week 80 in Overall Hand Pain Related to Finger Ulcers | Overall hand pain related to finger ulcers was assessed by the patient using a Visual Analogue Scale. Patients were instructed to score their pain by marking on the continuous 10-cm scale, where 0 (left) was no pain and 100 (right) very severe pain, in response to the question, "How much pain have you had because of your finger ulcers in the past week?" The investigator measured the distance in millimeters between 0 and the patient mark with the ruler provided and recorded the distance. | number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 110, 94, 89, 81, 76, and 73, respectively | Posted | Mean | Standard Deviation | mm | 80 weeks |
|
|
|
| Primary | Mean Change From Baseline at Each 16 Week Interval up to Week 80 in the UK Systemic Sclerosis Functional Score (UKFS) | UKFS relates to upper and lower extremity function and muscle weakness. For each item, the patient indicated the responses that best described their current ability: "able to perform in a normal manner," "able to perform with alteration in style," "can only manage with difficulty," and "impossible to achieve." Each response was given an integer from 0 (able to perform in a normal manner) to 3 (impossible to achieve), and the sum of individual responses provided an overall score of 0 to 33. Missing values were replaced with the worst value the patient reported on the other items at that visit. | number of participants at baseline, week 16, week 32, week 48, week 64, and week 80 was 116, 98, 93, 84, 82, and 78, respectively | Posted | Mean | Standard Deviation | score on a scale | 80 weeks |
|
|
|
| Primary | Total Number of New Digital Ulcers (DUs) Per Patient Observed by the Investigator at Planned Visits | The total number of new DUs per patient observed by the investigator at planned visits and new transient DUs recorded in the patient diary (a patient diary was used to record DUs that might appear and disappear between two planned visits) were assessed at each clinic visit | One patient did not have a DU at baseline (number of patients assessed at Weeks 0-4,4-8,8-16,16-24,24-32,32-40,40-48,48-56,56-64,64-72, and 72-80 were 114, 107, 103, 100, 97, 94, 88, 87, 86, 86, and 83, respectively. | Posted | Number | number of new digital ulcers | At planned visits up to week 80 |
|
|
|
| Secondary | Adverse Events up to 24 Hours After Last Study Medication | Number of patients with at least one treatment-emergent adverse event. All adverse events that occurred after study drug initiation and up to 24 hours after study drug discontinuation were to be recorded. | Study population | Posted | Number | participants | 80 weeks |
|
|
|
| Secondary | Adverse Events Leading to Permanent Discontinuation of the Study Medication | Number of patients with an adverse event leading to permanent discontinuation of the study treatment | Study population | Posted | Number | participants | 80 weeks |
|
|
|
| Secondary | Serious Adverse Events up to 28 Days After Last Study Medication | Number of patients with at least one treatment-emergent serious adverse event (TESAE) were reported. TESAEs are serious AEs that occurred after study drug initiation and up to 28 days after study drug discontinuation. More details on the SAEs are provided in the specific Adverse Events Section | Posted | Number | Participants | 80 weeks |
|
|
|
| 6 |
| 116 |
| 45 |
| 116 |
| 111 |
| 116 |
| INFECTED SKIN ULCER | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| CELLULITIS | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| DEVICE RELATED INFECTION | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| SEPSIS | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| ABSCESS LIMB | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| APPENDICITIS | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| BRONCHITIS | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| CATHETER SITE INFECTION | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| DIVERTICULITIS | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| GANGRENE | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| GASTROENTERITIS | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| HEPATITIS B | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| HERPES ZOSTER | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| INFLUENZA | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| LOBAR PNEUMONIA | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| LOCALISED INFECTION | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| OSTEOMYELITIS | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| VIRAL PERICARDITIS | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| VIRAL UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| PULMONARY FIBROSIS | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| PULMONARY HYPERTENSION | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| ACUTE RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| PLEURAL EFFUSION | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| PNEUMONITIS | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| PNEUMOTHORAX | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| PULMONARY ARTERIAL HYPERTENSION | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| ABDOMINAL PAIN LOWER | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| COLITIS ISCHAEMIC | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| DIVERTICULUM INTESTINAL | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| FAECALOMA | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| GASTRITIS | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| GASTROINTESTINAL MOTILITY DISORDER | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| ILEUS | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| INTESTINAL OBSTRUCTION | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| OESOPHAGITIS HAEMORRHAGIC | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| INTERVERTEBRAL DISC PROTRUSION | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| SCLERODERMA | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| MUSCULAR WEAKNESS | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| MYOSITIS | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| OSTEOARTHRITIS | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| RHEUMATOID ARTHRITIS | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| ROTATOR CUFF SYNDROME | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| SYSTEMIC SCLEROSIS | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| TENOSYNOVITIS | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| ADVERSE DRUG REACTION | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| CHEST PAIN | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| DEVICE DISLOCATION | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| DRUG WITHDRAWAL SYNDROME | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| IMPAIRED HEALING | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| PAIN | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| SUPRAPUBIC PAIN | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| SKIN ULCER | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| PYODERMA GANGRENOSUM | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| SKIN DISCOLOURATION | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| SKIN NECROSIS | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| PERIPHERAL ISCHAEMIA | Vascular disorders | MedDRA (13.0) | Systematic Assessment |
|
| EXTREMITY NECROSIS | Vascular disorders | MedDRA (13.0) | Systematic Assessment |
|
| FEMORAL ARTERY OCCLUSION | Vascular disorders | MedDRA (13.0) | Systematic Assessment |
|
| HYPOTENSION | Vascular disorders | MedDRA (13.0) | Systematic Assessment |
|
| CARDIAC FAILURE CONGESTIVE | Cardiac disorders | MedDRA (13.0) | Systematic Assessment |
|
| ACUTE CORONARY SYNDROME | Cardiac disorders | MedDRA (13.0) | Systematic Assessment |
|
| ATRIAL FIBRILLATION | Cardiac disorders | MedDRA (13.0) | Systematic Assessment |
|
| CARDIAC ARREST | Cardiac disorders | MedDRA (13.0) | Systematic Assessment |
|
| MYOCARDIAL INFARCTION | Cardiac disorders | MedDRA (13.0) | Systematic Assessment |
|
| MYOCARDITIS | Cardiac disorders | MedDRA (13.0) | Systematic Assessment |
|
| CAROTID ARTERY STENOSIS | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| CEREBROVASCULAR ACCIDENT | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| DIZZINESS POSTURAL | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| HYPOAESTHESIA | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| LUMBAR RADICULOPATHY | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| PARAESTHESIA | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| ARTHRODESIS | Surgical and medical procedures | MedDRA (13.0) | Systematic Assessment |
|
| FINGER AMPUTATION | Surgical and medical procedures | MedDRA (13.0) | Systematic Assessment |
|
| FOOT AMPUTATION | Surgical and medical procedures | MedDRA (13.0) | Systematic Assessment |
|
| HIP ARTHROPLASTY | Surgical and medical procedures | MedDRA (13.0) | Systematic Assessment |
|
| LUNG TRANSPLANT | Surgical and medical procedures | MedDRA (13.0) | Systematic Assessment |
|
| REVISION OF INTERNAL FIXATION | Surgical and medical procedures | MedDRA (13.0) | Systematic Assessment |
|
| ASBESTOSIS | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
|
| JOINT INJURY | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
|
| PROCEDURAL PAIN | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
|
| VASCULAR GRAFT OCCLUSION | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA (13.0) | Systematic Assessment |
|
| IRON DEFICIENCY ANAEMIA | Blood and lymphatic system disorders | MedDRA (13.0) | Systematic Assessment |
|
| SCLERODERMA RENAL CRISIS | Renal and urinary disorders | MedDRA (13.0) | Systematic Assessment |
|
| RENAL FAILURE ACUTE | Renal and urinary disorders | MedDRA (13.0) | Systematic Assessment |
|
| DEHYDRATION | Metabolism and nutrition disorders | MedDRA (13.0) | Systematic Assessment |
|
| MALNUTRITION | Metabolism and nutrition disorders | MedDRA (13.0) | Systematic Assessment |
|
| ALCOHOLIC PSYCHOSIS | Psychiatric disorders | MedDRA (13.0) | Systematic Assessment |
|
| DEPRESSION | Psychiatric disorders | MedDRA (13.0) | Systematic Assessment |
|
| HEPATIC ENZYME INCREASED | Investigations | MedDRA (13.0) | Systematic Assessment |
|
| CHRONIC LYMPHOCYTIC LEUKAEMIA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (13.0) | Systematic Assessment |
|
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| INFECTED SKIN ULCER | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| LOCALISED INFECTION | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| HEADACHE | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| RASH | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| NASOPHARYNGITIS | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| OEDEMA PERIPHERAL | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| LIVER FUNCTION TEST ABNORMAL | Investigations | MedDRA (13.0) | Systematic Assessment |
|
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA (13.0) | Systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA (13.0) | Systematic Assessment |
|
| DYSPHAGIA | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| FATIGUE | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| BRONCHITIS | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| INSOMNIA | Psychiatric disorders | MedDRA (13.0) | Systematic Assessment |
|
| SINUSITIS | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| INFLUENZA | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| PYREXIA | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| GASTROOESOPHAGEAL REFLUX DISEASE | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| TENDONITIS | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| URINARY TRACT INFECTION | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA (13.0) | Systematic Assessment |
|
| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
|
| CELLULITIS | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| GASTROENTERITIS VIRAL | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| ASTHENIA | General disorders | MedDRA (13.0) | Systematic Assessment |
|
| DIZZINESS | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
|
| HAEMOGLOBIN DECREASED | Investigations | MedDRA (13.0) | Systematic Assessment |
|
| HERPES ZOSTER | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
|
| MOUTH ULCERATION | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
|
| WEIGHT DECREASED | Investigations | MedDRA (13.0) | Systematic Assessment |
|
Any study-related article or abstract written independently by investigators should be submitted to Actelion for review at least 60 days prior to submission for publication or presentation.
| D001555 |
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
|
| change from baseline to week 64 |
|
| change from baseline to week 80 |
|
|
| change from baseline to week 64 |
|
| change from baseline to week 80 |
|
|
| change from baseline to week 64 |
|
| change from baseline to week 80 |
|
|
| change from baseline to week 64 |
|
| change from baseline to week 80 |
|
|
| change from baseline to week 64 |
|
| change from baseline to week 80 |
|
|
| change from baseline to week 64 |
|
| change from baseline to week 80 |
|
|
| change from baseline to week 64 |
|
| change from baseline to week 80 |
|
|
| change from baseline to week 64 |
|
| change from baseline to week 80 |
|
|
| change from baseline to week 64 |
|
| change from baseline to week 80 |
|
|
| change from baseline to week 64 |
|
| change from baseline to week 80 |
|
| Week 4-8 |
|
| Week 8-16 |
|
| Week 16-24 |
|
| Week 24-32 |
|
| Week 32-40 |
|
| Week 40-48 |
|
| Week 48-56 |
|
| Week 56-64 |
|
| Week 64-72 |
|
| Week 72-80 |
|