Trial Outcomes & Findings for A Study to Assess the Effect of Tocilizumab Plus Methotrexate on Safety and Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis (NCT NCT00754572)
NCT ID: NCT00754572
Last Updated: 2015-05-15
Results Overview
ACR50 is defined as 50 percent (%) improvement in: a) Swollen Joints Count (SJC) and Tender Joints Count (TJC) and b) Three of the following 5 assessments: 1. Participant's global assessment of pain by Visual Analog Scale (VAS) 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) 5. Acute phase reactant levels - Erythrocyte Sedimentation Rate or C-Reactive Protein (ESR or CRP)
COMPLETED
PHASE3
418 participants
Week 24
2015-05-15
Participant Flow
Participant milestones
| Measure |
Tocilizumab
Participants received tocilizumab 8 milligrams per kilogram (mg/kg) intravenously (iv), once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throuhgout the study.
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|---|---|
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Overall Study
STARTED
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418
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Overall Study
COMPLETED
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347
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Overall Study
NOT COMPLETED
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71
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Reasons for withdrawal
| Measure |
Tocilizumab
Participants received tocilizumab 8 milligrams per kilogram (mg/kg) intravenously (iv), once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throuhgout the study.
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Overall Study
Adverse Event
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19
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Overall Study
Other
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39
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Overall Study
Protocol Violation
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3
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Overall Study
Withdrawal by Subject
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3
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Overall Study
Lack of Efficacy
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2
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Overall Study
Death
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1
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Overall Study
Administrative Reason
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3
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Overall Study
Lost to Follow-up
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1
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Baseline Characteristics
A Study to Assess the Effect of Tocilizumab Plus Methotrexate on Safety and Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Tocilizumab
n=418 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Age, Continuous
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48.69 years
STANDARD_DEVIATION 12.36 • n=99 Participants
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Sex: Female, Male
Female
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371 Participants
n=99 Participants
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Sex: Female, Male
Male
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47 Participants
n=99 Participants
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PRIMARY outcome
Timeframe: Week 24Population: ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
ACR50 is defined as 50 percent (%) improvement in: a) Swollen Joints Count (SJC) and Tender Joints Count (TJC) and b) Three of the following 5 assessments: 1. Participant's global assessment of pain by Visual Analog Scale (VAS) 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) 5. Acute phase reactant levels - Erythrocyte Sedimentation Rate or C-Reactive Protein (ESR or CRP)
Outcome measures
| Measure |
Tocilizumab
n=381 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24
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73.23 percentage of participants
Interval 68.78 to 77.67
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SECONDARY outcome
Timeframe: Week 24Population: ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
ACR20 and ACR70 are defined as 20 and 70 percent improvement respectively in: a) SJC and TJC and b) Three of the following 5 assessments: 1. Participant's global assessment of pain by VAS 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by HAQ-DI 5. Acute phase reactant (ESR or CRP)
Outcome measures
| Measure |
Tocilizumab
n=381 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Percentage of Participants With ACR20 and ACR70 Response at Week 24
ACR 20
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90.55 percentage of participants
Interval 87.61 to 93.49
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Percentage of Participants With ACR20 and ACR70 Response at Week 24
ACR 70
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50.39 percentage of participants
Interval 45.37 to 55.41
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SECONDARY outcome
Timeframe: Baseline and Week 24Population: Data were not analyzed because of inconsistencies in the pooled data between countries.
ACR20, ACR50 and ACR70 are defined as 20, 50 and 70 percent improvement respectively in: a) SJC and TJC and b) Three of the following 5 assessments: 1. Participant's global assessment of pain by VAS 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by HAQ-DI 5. Acute phase reactant (ESR or CRP)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Data were not analyzed because of inconsistencies in the pooled data between countries.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
The number of swollen joints (66 joint count) were scored as swollen=1 and not swollen=0, and the number of tender joints (68 joint count ) were scored as tender=1 and not tender=0, and counted. Scores ranged from 0 to 66 for swollen joint counts and from 0 to 68 for tender joint counts. A positive change from baseline represents an improvement (a reduction in the number of swollen or tender joints).
Outcome measures
| Measure |
Tocilizumab
n=384 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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SJC and TJC at Baseline and Week 24
TJC-Baseline
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25.06 joints
Standard Deviation 13.83
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SJC and TJC at Baseline and Week 24
TJC-Week 24
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4.57 joints
Standard Deviation 7.57
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SJC and TJC at Baseline and Week 24
SJC-Baseline
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16.09 joints
Standard Deviation 8.69
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SJC and TJC at Baseline and Week 24
SJC-Week 24
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2.56 joints
Standard Deviation 4.26
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SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
The number of swollen joints (66 joint count) were scored as swollen=1 and not swollen=0, and the number of tender joints (68 joint count ) were scored as tender=1 and not tender=0, and counted. Scores ranged from 0 to 66 for swollen joint counts and from 0 to 68 for tender joint counts. A positive change from baseline represents an improvement (a reduction in the number of swollen or tender joints).
Outcome measures
| Measure |
Tocilizumab
n=384 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Percent Change From Baseline in SJC and TJC at Week 24
TJC
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81.2 percent change
Standard Deviation 28.1
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Percent Change From Baseline in SJC and TJC at Week 24
SJC
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84.8 percent change
Standard Deviation 22.5
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SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population; All participants with endpoint values collected at the specified timepoints were included in the analysis. number (n) equals (=) number of participants analyzed for the given parameter at the specified time point.
The participants assessed their pain using a 0 to 100 millimeter (mm) VAS. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". The participants marked the line corresponding to the level of their pain and the distance from the left edge was measured. A positive change from baseline represents an improvement.
Outcome measures
| Measure |
Tocilizumab
n=384 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Pain as Assessed by the Participant at Baseline and Week 24
Baseline (n=384)
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68.01 mm
Standard Deviation 20.39
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Pain as Assessed by the Participant at Baseline and Week 24
Week 24 (n=381)
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22.94 mm
Standard Deviation 22.53
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SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population; All participants with endpoint values collected at Baseline and Week 24 were included in the analysis.
The participants assessed their pain using a 0 to 100 millimeter (mm) VAS. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". The participants marked the line corresponding to the level of their pain and the distance from the left edge was measured. A positive change from baseline represents an improvement.
Outcome measures
| Measure |
Tocilizumab
n=381 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Percent Change From Baseline in Pain as Assessed by the Participant at Week 24
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54.2 percent change
Standard Deviation 177.0
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SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population. All participants with endpoint values collected at the specified timepoints were included in the analysis. n= number of participants analyzed for the given parameter at the specified time point.
The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A positive change from baseline represents an improvement (reduced level of disease activity).
Outcome measures
| Measure |
Tocilizumab
n=384 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Participant's Global Assessment of Disease Activity at Baseline and Week 24
Baseline (n=384)
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69.46 mm
Standard Deviation 20.84
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Participant's Global Assessment of Disease Activity at Baseline and Week 24
Week 24 (n=381)
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23.60 mm
Standard Deviation 22.68
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SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A positive change from baseline represents an improvement (reduced level of disease activity).
Outcome measures
| Measure |
Tocilizumab
n=381 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Percent Change From Baseline in Participant's Global Assessment of Disease Activity at Week 24
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61.7 percent change
Standard Deviation 43.1
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SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population. All participants with endpoint values collected at the specified timepoints were included in the analysis. n=number of participants analyzed for the given parameter at the specified visit.
The physician's global assessment of disease activity is assessed on a 0 to 100 mm VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity). The physicians marked the line corresponding to their assessment and the distance from the left edge was measured. A positive change from baseline represents an improvement (reduced level of disease activity).
Outcome measures
| Measure |
Tocilizumab
n=384 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Physician's Global Assessment of Disease Activity at Baseline and Week 24
Baseline (n=384)
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67.32 mm
Standard Deviation 16.64
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Physician's Global Assessment of Disease Activity at Baseline and Week 24
Week 24 (n=381)
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17.92 mm
Standard Deviation 18.16
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SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
The physician's global assessment of disease activity is assessed on a 0 to 100 mm VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity). The physicians marked the line corresponding to their assessment and the distance from the left edge was measured. A positive change from baseline represents an improvement (reduced level of disease activity).
Outcome measures
| Measure |
Tocilizumab
n=381 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Percent Change From Baseline in Physician's Global Assessment of Disease Activity at Week 24
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71.2 percent change
Standard Deviation 38.7
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SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population. All participants with endpoint values collected at the specified timepoints were included in the analysis. n=number of participants analyzed for the given parameter at the specified time point.
HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 =without difficulties; 1= with some difficulties; 2=with great difficulties; and 3= unable to perform these actions at all. Minimum score was 0, maximum score was 3. A positive change from baseline represents an improvement (reduced level of impairment).
Outcome measures
| Measure |
Tocilizumab
n=384 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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HAQ-DI at Baseline and Week 24
Baseline (n=384)
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1.70 units on a scale
Standard Deviation 0.63
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HAQ-DI at Baseline and Week 24
Week 24 (n=376)
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0.79 units on a scale
Standard Deviation 0.68
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SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population. All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. A positive change from baseline represents an improvement (reduced level of impairment).
Outcome measures
| Measure |
Tocilizumab
n=376 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Percent Change From Baseline in HAQ-DI at Week 24
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52.0 percent change
Standard Deviation 49.3
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SECONDARY outcome
Timeframe: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24Population: ITT Population; All participants with endpoint values collected were included in the analysis.
ACR-n was defined as the lowest of 3 values (the percent change in the swollen joint count, the percent change in the tender joint count, and the median of the other 5 measures in the ACR core data set which included Participant's global assessment of pain (VAS), Participant's global assessment of disease activity (VAS), Investigator/Physician's global assessment of disease activity (VAS), Participant's assessment of disability measured by the HAQ-DI Acute phase reactant levels - ESR or CRP). Therefore, a percentage value was assigned to each participant at each timepoint. AUC was calculated for each participant from baseline to Week 112. Mean and standard deviation values are are provided in percent\*years.
Outcome measures
| Measure |
Tocilizumab
n=391 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Area Under The Curve (AUC) of the ACR(n)
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20.8 percent*years
Standard Deviation 9.4
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SECONDARY outcome
Timeframe: Week 2Population: ITT Population; All participants with endpoint values collected at Week 2 were included in the analysis.
ACR20 is defined as 20% improvement in: a) SJC and TJC and b) Three of the following 5 assessments: 1. Participant's global assessment of pain (VAS) 2. Participant's global assessment of disease activity (VAS) 3. Investigator/Physician's global assessment of disease activity (VAS) 4. Participant's assessment of disability measured by the HAQ-DI 5. Acute phase reactant levels - ESR or CRP
Outcome measures
| Measure |
Tocilizumab
n=389 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Percentage of Participants Achieving ACR20 Response
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40.10 percentage of participants
Interval 35.23 to 44.97
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SECONDARY outcome
Timeframe: Weeks 2, 4, 8, 12, 16, 20, 24Population: ITT Population; All participants with endpoint values collected were included in the analysis.
The probability of ACR positive response was determined using the GEE.
Outcome measures
| Measure |
Tocilizumab
n=418 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 12 Odds ACR70
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0.41 odds
Interval 0.34 to 0.51
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 2 Odds ACR50
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0.10 odds
Interval 0.07 to 0.14
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 4 Odds ACR50
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0.33 odds
Interval 0.27 to 0.42
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 8 Odds ACR50
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0.87 odds
Interval 0.72 to 1.05
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 12 Odds ACR50
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1.39 odds
Interval 1.14 to 1.69
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 16 Odds ACR50
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1.55 odds
Interval 1.28 to 1.89
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 20 Odds ACR50
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1.86 odds
Interval 1.52 to 2.27
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 24 Odds ACR50
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2.39 odds
Interval 1.93 to 2.95
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 2 Odds ACR20
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0.63 odds
Interval 0.51 to 0.76
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 4 Odds ACR20
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1.50 odds
Interval 1.24 to 1.83
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 8 Odds ACR20
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4.80 odds
Interval 3.73 to 6.19
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 12 Odds ACR20
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4.80 odds
Interval 3.73 to 6.19
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 16 Odds ACR20
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4.65 odds
Interval 3.61 to 5.97
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 20 Odds ACR20
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6.46 odds
Interval 4.88 to 8.56
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 24 Odds ACR20
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6.88 odds
Interval 5.16 to 9.18
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 4 Odds ACR70
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0.08 odds
Interval 0.06 to 0.12
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 8 Odds ACR70
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0.27 odds
Interval 0.21 to 0.34
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 16 Odds ACR70
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0.53 odds
Interval 0.44 to 0.65
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 20 Odds ACR70
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0.75 odds
Interval 0.62 to 0.91
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Odds Estimates for ACR Positive Response in Generalized Estimating Equation (GEE) Models
Week 24 Odds ACR70
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0.92 odds
Interval 0.76 to 1.12
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SECONDARY outcome
Timeframe: Baseline and Week 24Population: ITT Population; All participants with endpoint values collected at both baseline and Week 24 were included in the analysis.
DAS28 calculated from the number of SJC and TJC using the 28 joints count, the ESR (mm/hour) and participant's global assessment of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 (less than or equal to ) ≤3.2 = low disease activity, DAS28 (greater than) \>3.2 to 5.1 = moderate to high disease activity.
Outcome measures
| Measure |
Tocilizumab
n=399 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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|---|---|
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Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) at Week 24
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4.4 score on a scale
Standard Deviation 1.6
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SECONDARY outcome
Timeframe: Week 24Population: ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
DAS28- based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline \>1.2 with DAS28 \< 3.2; moderate response: change from baseline \>1.2 with DAS28 \>3.2 to \<5.1 or change from baseline \>0.6 to \<1.2 with DAS28 \<5.1; No response: change from baseline \< 0.6 or change from baseline \>0.6 and \<1.2 with DAS28 \>5.1.
Outcome measures
| Measure |
Tocilizumab
n=399 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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|---|---|
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Percentage of Participants With a Response by Categorical DAS28 Responses According to The European League Against Rheumatism (EULAR Response) at Week 24
Good Response
|
68.17 Percentage of Participants
Interval 63.6 to 72.74
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Percentage of Participants With a Response by Categorical DAS28 Responses According to The European League Against Rheumatism (EULAR Response) at Week 24
Moderate Response
|
29.57 Percentage of Participants
Interval 25.1 to 34.05
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Percentage of Participants With a Response by Categorical DAS28 Responses According to The European League Against Rheumatism (EULAR Response) at Week 24
No Response
|
2.26 Percentage of Participants
Interval 0.8 to 3.71
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SECONDARY outcome
Timeframe: Weeks 2, 4, 8, 12, 16, 20 and 24Population: ITT Population; All participants with endpoint values collected were included in the analysis.
The AUC was computed using the trapezoidal rule, considering baseline value as 0, through NCSS software. For each participant, AUC for DAS28 units was calculated. Each individual AUC DAS28 value was divided by 52 to have the conversion of AUC DAS28 in unit weeks to AUC DAS28 in unit years, as 1 week is approximately 1/52 years. The set of individual AUC DAS28 was computed as summary statistics.
Outcome measures
| Measure |
Tocilizumab
n=416 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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|---|---|
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AUC of DAS28
|
11.8 scores on a scale * years
Standard Deviation 4.2
|
SECONDARY outcome
Timeframe: Week 24Population: ITT Population. All participants with endpoint values collected at Week 24 were included in the analysis.
FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the participant's health status.
Outcome measures
| Measure |
Tocilizumab
n=403 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
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|---|---|
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Fatigue as Assessed Using the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue) Score at Week 24
|
39.9 score on a scale
Standard Deviation 9.4
|
SECONDARY outcome
Timeframe: Week 24Population: ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and participant's global assessment of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 (less than or equal to ) ≤3.2 = low disease activity, DAS28 (greater than) \>3.2 to 5.1 = moderate to high disease activity and DAS28\<2.6 = remission
Outcome measures
| Measure |
Tocilizumab
n=409 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
|
|---|---|
|
Percentage of Participants Achieving Remission (DAS28 Less Than [<] 2.6) at Week 24
|
48.41 percentage of participants
Interval 43.57 to 53.25
|
SECONDARY outcome
Timeframe: Week 24Population: ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. Total of 3 variables were analyzed (2 composite subscales and vitality score). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Outcome measures
| Measure |
Tocilizumab
n=378 Participants
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
|
|---|---|
|
Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24
General Health
|
42.5 score on a scale
Standard Deviation 12.9
|
|
Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24
Physical functioning
|
63.0 score on a scale
Standard Deviation 24.2
|
|
Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24
Role limitations due to physical health
|
64.0 score on a scale
Standard Deviation 23.9
|
|
Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24
Role limitations due to emotional problems
|
66.0 score on a scale
Standard Deviation 24.1
|
|
Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24
Energy/fatigue
|
48.9 score on a scale
Standard Deviation 10.6
|
|
Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24
Emotional well-being
|
54.5 score on a scale
Standard Deviation 10.3
|
|
Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24
Social functioning
|
38.2 score on a scale
Standard Deviation 12.7
|
|
Quality of Life (QoL) Assessed by Short-Form 36 (SF-36) at Week 24
Pain
|
63.6 score on a scale
Standard Deviation 24.8
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Data were not analyzed because of inconsistencies in the pooled data between countries.
Outcome measures
Outcome data not reported
Adverse Events
Tocilizumab
Serious adverse events
| Measure |
Tocilizumab
n=418 participants at risk
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
|
|---|---|
|
Infections and infestations
Pneumonia
|
0.72%
3/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Immune system disorders
Hypersensitivity
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Gastrointestinal disorders
Constipation
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Blood and lymphatic system disorders
Anaemia
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Cardiac disorders
Bradicardia
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Infections and infestations
Bronchitis
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Gastrointestinal disorders
Chronic gastrointestinal bleeding
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Gastrointestinal disorders
Gastritis
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Cardiac disorders
Myocardial infarction
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Renal and urinary disorders
Pyelonephritis acute NOS
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Infections and infestations
Septic shock
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Metabolism and nutrition disorders
Dehydration
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Nervous system disorders
Headache
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Blood and lymphatic system disorders
Leukopenia NOS
|
0.48%
2/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Infections and infestations
Appendicitis
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Respiratory, thoracic and mediastinal disorders
Asthmatic crisis
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Infections and infestations
Herpes zoster
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Infections and infestations
Cellulitis
|
0.72%
3/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc herniation
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Musculoskeletal and connective tissue disorders
Intervertebral discitis
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Injury, poisoning and procedural complications
Fracture
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Hepatobiliary disorders
Cholecystitis
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
General disorders
Abscess
|
0.24%
1/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
Other adverse events
| Measure |
Tocilizumab
n=418 participants at risk
Participants received tocilizumab 8 mg/kg iv, once every 4 weeks for a total of 6 infusions along with methotrexate 10-25 mg weekly, orally or parenterally. The dose of methotrexate should have remained stable throughout the study.
|
|---|---|
|
Metabolism and nutrition disorders
Hypercholesterolemia
|
17.0%
71/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Investigations
Hepatic enzyme increased
|
16.7%
70/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Nervous system disorders
Headache
|
9.8%
41/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Infections and infestations
Urinary tract infection
|
9.8%
41/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
9.3%
39/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Vascular disorders
Hypertension
|
7.7%
32/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Infections and infestations
Influenza
|
7.7%
32/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Infections and infestations
Pharyngitis
|
7.2%
30/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Blood and lymphatic system disorders
Leukopenia NOS
|
6.0%
25/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.3%
22/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Gastrointestinal disorders
Nausea
|
5.3%
22/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Gastrointestinal disorders
Stomatitis
|
5.3%
22/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.0%
21/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Investigations
Blood bilirubin increased
|
4.5%
19/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
|
Infections and infestations
Upper respiratory tract infection
|
4.5%
19/418 • Adverse events were recorded from the date of first dose of drug administration until the end of study
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER