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This multicenter, open-label, single arm study will assess the safety and efficacy of RoActemra/Actemra (tocilizumab) in combination with methotrexate in patients with active rheumatoid arthritis who have an inadequate response to non-biologic disease-modifying antirheumatic drugs (DMARDs). Patients will receive RoActemra/Actemra 8 mg/kg intravenously every 4 weeks for a total of 6 infusions plus methotrexate 10-25 mg orally weekly. Anticipated time on study treatment is 24 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Arm | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tocilizumab [RoActemra/Actemra] | Drug | 8 mg/kg iv every 4 weeks for a total of 6 infusions |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving Low Disease Activity Score | Disease Activity Score using 28-Joint Count (DAS28) was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and global health assessment (participant-rated global assessment of disease activity using 10-mm visual analog scale [VAS]); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 less than or equal to (≤3.2) equals (=) low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity. | Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Achieve Low Disease Activity (DAS28 ≤3.2) | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 ≤3.2 = low disease activity; time to low disease activity was calculated as the time in weeks from the date of first infusion to the first achievement of DAS28 ≤3.2 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bandung | 40161 | Indonesia | ||||
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| ID | Title | Description |
|---|---|---|
| FG000 | Tocilizumab + Methotrexate (MTX) | Participants received tocilizumab 8 milligrams per kilogram (mg/kg) (minimum dose 480 mg, maximum dose 800 mg), intravenously (IV), once every 4 weeks (maximum number of infusions received was 6) and MTX, 10-25 mg per week, at a stable dose; the dose and route of administration of MTX at entry in the study was to be continued without change while on study unless an adjustment was necessary for safety reasons. All participants treated with MTX received either folic acid or leucovorin according to the manufacturer's recommendations. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| methotrexate |
| Drug |
10-25 mg orally weekly |
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| Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 |
| Percentage of Participants With a Clinically Significant Improvement in DAS28 Score | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity; a clinically significant improvement in DAS28 score was defined as a reduction of at least 1.2 units. | Weeks 4, 8, 12, 16, 20 and 24 |
| Time to Clinically Significant Improvement in DAS28 | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity; a clinically significant improvement is a reduction in DAS28 score of at least 1.2 units. Time to clinically significant improvement was determined in weeks from the date of first infusion to the date of first achievement of reduction of 1.2 units in DAS28. | Weeks 4, 8, 12, 16, 20 and 24 |
| Percentage of Participants Achieving DAS28 Remission (DAS28 <2.6) | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Remission was defined as DAS28 <2.6. | Baseline and Weeks 4, 8, 12, 16, 20, and 24 |
| Time to Achieve DAS28 Remission (DAS28 <2.6) | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 remission was defined as DAS28 <2.6. Time to achieve remission was calculated in weeks as the time from the date of first infusion to the date of first achieving remission. | Weeks 4, 8, 12, 16, 20 and 24 |
| Percentage of Participants With DAS28 <3.2 by Visit | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 ≤3.2 = low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity. | Baseline and Weeks 4, 8, 12, 16, 20, and 24 |
| Percentage of Participants Achieving American College of Rheumatology (ACR) 20%, 50%, and 70% Improvement (ACR20, ACR50, or ACR70) Response | ACR20/50/70 response was defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in swollen/tender joint count (66 joints assessed for swelling and 68 joints assessed for tenderness) as well as improvement in at least 3 of the 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the health assessment questionnaire [HAQ]); and acute phase response: C-reactive protein (CRP) or ESR. | Week 24 |
| Erythrocyte Sedimentation Rate | Erythrocyte Sedimentation rate was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr. | Baseline, Weeks 4, 8, 12, 16, 20, and 24 |
| C-Reactive Protein Levels | CRP levels were measured in milligrams/liter (mg/L) and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L. | Baseline, Weeks 4, 8, 12,16, 20, and 24 |
| Central Jakarta |
| 10430 |
| Indonesia |
| East Java | Indonesia |
| Malang | 65111 | Indonesia |
| Yogyakarta | 55284 | Indonesia |
| COMPLETED |
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| NOT COMPLETED |
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Intent to treat (ITT) population: all participants included in the study who received at least one dose of study medication. Participants prematurely withdrawn from the study will be considered as nonresponders at the end of the study in all analyses of treatment response variables.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tocilizumab + MTX | Participants received tocilizumab 8 mg/kg (minimum dose 480 mg, maximum dose 800 mg), IV, once every 4 weeks (maximum number of infusions received was 6) and MTX, 10-25 mg per week, at a stable dose; the dose and route of administration of MTX at entry in the study was to be continued without change while on study unless an adjustment was necessary for safety reasons. All participants treated with MTX received either folic acid or leucovorin according to the manufacturer's recommendations. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| 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 | Percentage of Participants Achieving Low Disease Activity Score | Disease Activity Score using 28-Joint Count (DAS28) was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and global health assessment (participant-rated global assessment of disease activity using 10-mm visual analog scale [VAS]); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 less than or equal to (≤3.2) equals (=) low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity. | ITT population: All participants randomized in the study who received administration of at least one dose of the study drug and who had the last week 24 assessment performed. | Posted | Number | percentage of participants | Week 24 |
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| Secondary | Time to Achieve Low Disease Activity (DAS28 ≤3.2) | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 ≤3.2 = low disease activity; time to low disease activity was calculated as the time in weeks from the date of first infusion to the first achievement of DAS28 ≤3.2 | ITT Population | Posted | Mean | Standard Deviation | weeks | Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 |
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| Secondary | Percentage of Participants With a Clinically Significant Improvement in DAS28 Score | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity; a clinically significant improvement in DAS28 score was defined as a reduction of at least 1.2 units. | ITT Population | Posted | Number | percentage of participants | Weeks 4, 8, 12, 16, 20 and 24 |
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| Secondary | Time to Clinically Significant Improvement in DAS28 | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity; a clinically significant improvement is a reduction in DAS28 score of at least 1.2 units. Time to clinically significant improvement was determined in weeks from the date of first infusion to the date of first achievement of reduction of 1.2 units in DAS28. | ITT Population | Posted | Mean | Standard Deviation | weeks | Weeks 4, 8, 12, 16, 20 and 24 |
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| Secondary | Percentage of Participants Achieving DAS28 Remission (DAS28 <2.6) | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Remission was defined as DAS28 <2.6. | ITT Population | Posted | Number | percentage of participants | Baseline and Weeks 4, 8, 12, 16, 20, and 24 |
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| Secondary | Time to Achieve DAS28 Remission (DAS28 <2.6) | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 remission was defined as DAS28 <2.6. Time to achieve remission was calculated in weeks as the time from the date of first infusion to the date of first achieving remission. | ITT Population | Posted | Mean | Standard Deviation | weeks | Weeks 4, 8, 12, 16, 20 and 24 |
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| Secondary | Percentage of Participants With DAS28 <3.2 by Visit | DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hour) and global health assessment (participant-rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. DAS28 ≤3.2 = low disease activity, DAS28 >3.2 to 5.1 = moderate to high disease activity. | ITT Population | Posted | Number | percentage of participants | Baseline and Weeks 4, 8, 12, 16, 20, and 24 |
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| Secondary | Percentage of Participants Achieving American College of Rheumatology (ACR) 20%, 50%, and 70% Improvement (ACR20, ACR50, or ACR70) Response | ACR20/50/70 response was defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in swollen/tender joint count (66 joints assessed for swelling and 68 joints assessed for tenderness) as well as improvement in at least 3 of the 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the health assessment questionnaire [HAQ]); and acute phase response: C-reactive protein (CRP) or ESR. | ITT Population | Posted | Number | percentage of participants | Week 24 |
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| Secondary | Erythrocyte Sedimentation Rate | Erythrocyte Sedimentation rate was measured in mm/hour and was used to determine the acute phase response. Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr. | ITT Population | Posted | Mean | Standard Deviation | mm/hr | Baseline, Weeks 4, 8, 12, 16, 20, and 24 |
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| Secondary | C-Reactive Protein Levels | CRP levels were measured in milligrams/liter (mg/L) and were used to determine the acute phase response. A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L. | ITT Population | Posted | Mean | Standard Deviation | mg/L | Baseline, Weeks 4, 8, 12,16, 20, and 24 |
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Adverse events were recorded from the day of baseline evaluation until the end of study at Week 24.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tocilizumab + MTX | Participants received tocilizumab 8 mg/kg (minimum dose 480 mg, maximum dose 800 mg), IV, once every 4 weeks (maximum number of infusions received was 6) and MTX, 10-25 mg per week, at a stable dose; the dose and route of administration of MTX at entry in the study was to be continued without change while on study unless an adjustment was necessary for safety reasons. All participants treated with MTX received either folic acid or leucovorin according to the manufacturer's recommendations. | 2 | 39 | 37 | 39 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sepsis | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Gastroesophageal reflux disease | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Mouth ulceration | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Odynophagia | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Chills | General disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Fever | General disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Injection site ecchymosis | General disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Injection site haematoma | General disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Injection site pain | General disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Pain | General disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Hepatic enzyme increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Hypertriglyceridemia | Metabolism and nutrition disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Cold | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Influenza | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Pharyngitis | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Rhinitis | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Fungal infection | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
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| Herpes virus infection | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
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| Lobar pneumonia | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
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| Pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA (16.0) | Non-systematic Assessment |
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| Azotaemia | Renal and urinary disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Urticaria papular | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Leukocytosis | Blood and lymphatic system disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Pelvic inflammatory disease | Reproductive system and breast disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Pain ankle | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Weakness | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann- LaRoche | 800-821-8590 | genentech@druginfo.com |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C502936 | tocilizumab |
| D008727 | Methotrexate |
| ID | Term |
|---|---|
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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