A Study of Ocrelizumab in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Are Naive to Methotrexate (FILM)
Study Details
Study Description
Brief Summary
This study will evaluate the efficacy and safety of ocrelizumab, compared with placebo, in combination with methotrexate in patients with active rheumatoid arthritis who are naive to methotrexate. Patients will be randomized to receive placebo, ocrelizumab 200mg i.v. or ocrelizumab 500mg i.v. on Days 1 and 15. Repeat courses of i.v. treatment will be administered at weeks 24, 52 and 76. All patients will receive concomitant methotrexate (7.5 mg escalating to 20mg p.o. weekly). The anticipated time on study treatment is 2+ years, and the target sample size is 500+ individuals.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Placebo Comparator: Placebo Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. |
Drug: Placebo
Intravenous repeating dose
|
Experimental: Ocrelizumab 200 mg Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. |
Drug: Methotrexate
Oral repeating dose
Drug: Ocrelizumab
Intravenous repeating dose
|
Experimental: Ocrelizumab 500 mg Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. |
Drug: Methotrexate
Oral repeating dose
Drug: Ocrelizumab
Intravenous repeating dose
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in the Modified Total Sharp Score (mTSS) at Week 52 [Baseline to Week 52]
The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement.
Secondary Outcome Measures
- Percentage of Participants Without Radiographic Progression (RP) at Week 52 [Week 52]
RP was defined as a change from Baseline in the modified Total Sharp Score (mTSS) ≤ 0. The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement.
- Percentage of Participants With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Week 52 [Baseline to Week 52]
Improvement must be seen in tender (68) and swollen (66) joint counts. Joints were assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation. Improvement must also be seen in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "none" [symptom-free and no arthritis symptoms] and the extreme right end "maximum" [maximum arthritis disease activity]; patient assessment of pain in the previous 24 hours on a VAS (extreme left end of the line "none" and the extreme right end "unbearable"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C-reactive protein (CRP), or erythrocyte sedimentation rate if CRP was missing.
- Percentage of Participants in Disease Activity Score 28 (DAS28) Remission at Weeks 24 and 52 [Week 24 and Week 52]
A participant was in DAS28 remission if their DAS28 score < 2.6). The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where a higher score indicates more disease activity.
Eligibility Criteria
Criteria
Inclusion criteria:
-
Age ≥ 18
-
Rheumatoid arthritis for 3 months-5 years
-
Naive to methotrexate
-
If receiving steroids or NSAIDs, must be on a stable dose for 4 weeks prior to baseline
Exclusion criteria:
-
Rheumatic autoimmune disease or inflammatory joint disease other than RA
-
Prior receipt of any biologic therapy for RA
-
Concurrent treatment with any DMARD
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Genentech, Inc.
- Roche Pharma AG
Investigators
- Study Director: Wolfgang Dummer, M.D., Genentech, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ACT3984g
- WA20497
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | The study population comprised adult patients with active rheumatoid arthritis (RA) of at least 3 months' but less than 5 years' duration who were naïve to methotrexate. Additionally, patients were required to be naïve to any biologic therapy for RA prior to enrollment. |
Arm/Group Title | Placebo | Ocrelizumab 200 mg | Ocrelizumab 500 mg |
---|---|---|---|
Arm/Group Description | Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. |
Period Title: Overall Study | |||
STARTED | 210 | 200 | 203 |
COMPLETED | 183 | 180 | 185 |
NOT COMPLETED | 27 | 20 | 18 |
Baseline Characteristics
Arm/Group Title | Placebo | Ocrelizumab 200 mg | Ocrelizumab 500 mg | Total |
---|---|---|---|---|
Arm/Group Description | Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Total of all reporting groups |
Overall Participants | 207 | 196 | 202 | 605 |
Age (Years) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [Years] |
49.2
(12.43)
|
50.8
(13.17)
|
48.6
(12.29)
|
49.5
(12.66)
|
Sex/Gender, Customized (Number) [Number] | ||||
Female |
153
73.9%
|
154
78.6%
|
161
79.7%
|
468
77.4%
|
Male |
54
26.1%
|
42
21.4%
|
41
20.3%
|
137
22.6%
|
Outcome Measures
Title | Change From Baseline in the Modified Total Sharp Score (mTSS) at Week 52 |
---|---|
Description | The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement. |
Time Frame | Baseline to Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Placebo | Ocrelizumab 200 mg | Ocrelizumab 500 mg |
---|---|---|---|
Arm/Group Description | Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. |
Measure Participants | 193 | 187 | 194 |
Mean (Standard Deviation) [Units on a scale] |
1.59
(4.815)
|
0.66
(4.509)
|
0.27
(2.908)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, Ocrelizumab 200 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority | |
Comments | Pre-specified analysis | |
Statistical Test of Hypothesis | p-Value | 0.001 |
Comments | ||
Method | Van Elteren's test | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Ocrelizumab 500 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Non-Inferiority | |
Comments | Pre-specified analysis | |
Statistical Test of Hypothesis | p-Value | 0.0033 |
Comments | ||
Method | Van Elteren's test | |
Comments |
Title | Percentage of Participants Without Radiographic Progression (RP) at Week 52 |
---|---|
Description | RP was defined as a change from Baseline in the modified Total Sharp Score (mTSS) ≤ 0. The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement. |
Time Frame | Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Placebo | Ocrelizumab 200 mg | Ocrelizumab 500 mg |
---|---|---|---|
Arm/Group Description | Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. |
Measure Participants | 196 | 187 | 192 |
Number (95% Confidence Interval) [Percentage of participants] |
51
24.6%
|
66.3
33.8%
|
68.8
34.1%
|
Title | Percentage of Participants With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Week 52 |
---|---|
Description | Improvement must be seen in tender (68) and swollen (66) joint counts. Joints were assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation. Improvement must also be seen in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "none" [symptom-free and no arthritis symptoms] and the extreme right end "maximum" [maximum arthritis disease activity]; patient assessment of pain in the previous 24 hours on a VAS (extreme left end of the line "none" and the extreme right end "unbearable"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C-reactive protein (CRP), or erythrocyte sedimentation rate if CRP was missing. |
Time Frame | Baseline to Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Placebo | Ocrelizumab 200 mg | Ocrelizumab 500 mg |
---|---|---|---|
Arm/Group Description | Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. |
Measure Participants | 207 | 196 | 200 |
ACR20 |
57.5
27.8%
|
73
37.2%
|
71
35.1%
|
ACR50 |
39.6
19.1%
|
60.7
31%
|
54.5
27%
|
ACR70 |
20.3
9.8%
|
38.3
19.5%
|
38
18.8%
|
Title | Percentage of Participants in Disease Activity Score 28 (DAS28) Remission at Weeks 24 and 52 |
---|---|
Description | A participant was in DAS28 remission if their DAS28 score < 2.6). The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where a higher score indicates more disease activity. |
Time Frame | Week 24 and Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Placebo | Ocrelizumab 200 mg | Ocrelizumab 500 mg |
---|---|---|---|
Arm/Group Description | Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. | Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. |
Measure Participants | 207 | 196 | 200 |
Week 24 |
9.7
4.7%
|
19.9
10.2%
|
18
8.9%
|
Week 52 |
7.2
3.5%
|
27
13.8%
|
28
13.9%
|
Adverse Events
Time Frame | Baseline up to 30 months. | |||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | Safety population: All randomized participants who received at least 1 dose of study medication. | |||||||||||||||||||||||
Arm/Group Title | Placebo - Treatment Period | Placebo/Ocrelizumab 500 mg - Treatment Period | Ocrelizumab 200 mg - Treatment Period | Ocrelizumab 200 mg/Ocrelizumab 500 mg - Treatment Period | Ocrelizumab 500 mg - Treatment Period | Ocrelizumab 500 mg/Ocrelizumab 500 mg - Treatment Period | Placebo - Safety Follow-up Period | Placebo/Ocrelizumab 500 mg - Safety Follow-up Period | Ocrelizumab 200 mg - Safety Follow-up Period | Ocrelizumab 200 mg/Ocrelizumab 500 Mg-safety Follow-up Period | Ocrelizumab 500 mg - Safety Follow-up Period | Ocrelizumab 500 mg/Ocrelizumab 500 mg -Safety Follow-up Period | ||||||||||||
Arm/Group Description | Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76 and 78. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. | Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78 and ocrelizumab 500 mg intravenously on Weeks 100, 102, 124, and 126. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. | Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. | Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76 and ocrelizumab 500 mg intravenously on Weeks 100, 102, 124, and 126. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. | Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. | Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, 100, 102, 124, and 126. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. | Participants had received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76 and 78. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. | Participants had received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78 and ocrelizumab 500 mg intravenously on Weeks 100, 102, 124, and 126. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. | Participants had received Ocrelizumab intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. | Participants had received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76 and ocrelizumab 500 mg intravenously on Weeks 100, 102, 124, and 126. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. | Participants had received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76 and 78. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. | Participants had received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, 100, 102, 124, and 126. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. | ||||||||||||
All Cause Mortality |
||||||||||||||||||||||||
Placebo - Treatment Period | Placebo/Ocrelizumab 500 mg - Treatment Period | Ocrelizumab 200 mg - Treatment Period | Ocrelizumab 200 mg/Ocrelizumab 500 mg - Treatment Period | Ocrelizumab 500 mg - Treatment Period | Ocrelizumab 500 mg/Ocrelizumab 500 mg - Treatment Period | Placebo - Safety Follow-up Period | Placebo/Ocrelizumab 500 mg - Safety Follow-up Period | Ocrelizumab 200 mg - Safety Follow-up Period | Ocrelizumab 200 mg/Ocrelizumab 500 Mg-safety Follow-up Period | Ocrelizumab 500 mg - Safety Follow-up Period | Ocrelizumab 500 mg/Ocrelizumab 500 mg -Safety Follow-up Period | |||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/207 (0%) | 0/10 (0%) | 0/196 (0%) | 0/12 (0%) | 0/202 (0%) | 0/6 (0%) | 2/187 (1.1%) | 0/9 (0%) | 2/177 (1.1%) | 0/11 (0%) | 1/185 (0.5%) | 0/6 (0%) | ||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||
Placebo - Treatment Period | Placebo/Ocrelizumab 500 mg - Treatment Period | Ocrelizumab 200 mg - Treatment Period | Ocrelizumab 200 mg/Ocrelizumab 500 mg - Treatment Period | Ocrelizumab 500 mg - Treatment Period | Ocrelizumab 500 mg/Ocrelizumab 500 mg - Treatment Period | Placebo - Safety Follow-up Period | Placebo/Ocrelizumab 500 mg - Safety Follow-up Period | Ocrelizumab 200 mg - Safety Follow-up Period | Ocrelizumab 200 mg/Ocrelizumab 500 Mg-safety Follow-up Period | Ocrelizumab 500 mg - Safety Follow-up Period | Ocrelizumab 500 mg/Ocrelizumab 500 mg -Safety Follow-up Period | |||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 22/207 (10.6%) | 0/10 (0%) | 21/196 (10.7%) | 1/12 (8.3%) | 31/202 (15.3%) | 0/6 (0%) | 11/187 (5.9%) | 2/9 (22.2%) | 2/177 (1.1%) | 0/11 (0%) | 4/185 (2.2%) | 0/6 (0%) | ||||||||||||
Blood and lymphatic system disorders | ||||||||||||||||||||||||
Agranulocytosis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Anaemia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Anaemia haemolytic autoimmune | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Neutropenia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Leukopenia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Pancytopenia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Cardiac disorders | ||||||||||||||||||||||||
Acute myocardial infarction | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Coronary artery disease | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Arteriosclerosis coronary artery | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Atrial fibrillation | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Tachycardia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Supraventricular tachycardia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Congenital, familial and genetic disorders | ||||||||||||||||||||||||
Bronchogenic cyst | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Ear and labyrinth disorders | ||||||||||||||||||||||||
Deafness bilateral | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Vestibular disorder | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Endocrine disorders | ||||||||||||||||||||||||
Hyperthyroidism | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Eye disorders | ||||||||||||||||||||||||
Cataract | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Gastrointestinal disorders | ||||||||||||||||||||||||
Inguinal hernia | 2/207 (1%) | 2 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Abdominal hernia obstructive | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Constipation | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Gastritis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Gastrointestinal haemorrhage | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Gastrointestinal inflammation | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Intestinal obstruction | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Colitis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Upper gastrointestinal haemorrhage | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
General disorders | ||||||||||||||||||||||||
Non-cardiac chest pain | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Pyrexia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Hepatobiliary disorders | ||||||||||||||||||||||||
Cholelithiasis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 2/202 (1%) | 2 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Hepatic cirrhosis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 1/9 (11.1%) | 1 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Infections and infestations | ||||||||||||||||||||||||
Urinary tract infection | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 2/202 (1%) | 4 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Abdominal wall infection | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 1/12 (8.3%) | 1 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Abscess | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Acute tonsillitis | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Bacteraemia | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Bronchitis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Bronchopneumonia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Cellulitis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 1/177 (0.6%) | 1 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Diverticulitis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 1 |
Encephalitis viral | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Histoplasmosis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Infection | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Localised infection | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Pneumonia herpes viral | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Systemic candida | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Sepsis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 1/177 (0.6%) | 1 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Oesophageal candidiasis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Peritonitis bacterial | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 1/177 (0.6%) | 1 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Pharyngitis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Post procedural infection | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Urosepsis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Pneumonia | 3/207 (1.4%) | 3 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 2/202 (1%) | 2 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 1/9 (11.1%) | 1 | 2/177 (1.1%) | 2 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||||||||||||||||
Road traffic accident | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Accidental overdose | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Dislocation of vertebra | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Forearm fracture | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Hip fracture | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Infusion related reaction | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Limb traumatic amputation | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Upper limb fracture | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Joint dislocation | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Lower limb fracture | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Subdural haematoma | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||||||||||||||||
Hyperglycaemia | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Diabetes mellitus | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 1/177 (0.6%) | 1 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Hypoglycaemia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
Rheumatoid arthritis | 2/207 (1%) | 2 | 0/10 (0%) | 0 | 2/196 (1%) | 2 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 2/177 (1.1%) | 2 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Osteoarthritis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 2/196 (1%) | 2 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Back pain | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Osteonecrosis | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||
Squamous cell carcinoma of skin | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Colon cancer metastatic | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Prostate cancer | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Ovarian fibroma | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Nervous system disorders | ||||||||||||||||||||||||
Autonomic neuropathy | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 11 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Carpal tunnel syndrome | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Cerebellar infarction | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Cerebrovascular accident | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Leukoencephalopathy | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Dementia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 1/177 (0.6%) | 1 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Ischaemic cerebral infarction | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Psychiatric disorders | ||||||||||||||||||||||||
Depression | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 1/177 (0.6%) | 1 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Renal and urinary disorders | ||||||||||||||||||||||||
Nephrolithiasis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Renal failure | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Reproductive system and breast disorders | ||||||||||||||||||||||||
Benign prostatic hyperplasia | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
Interstitial lung disease | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 3/202 (1.5%) | 3 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Pulmonary alveolar haemorrhage | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Pulmonary eosinophilia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Vocal cord polyp | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Asthma | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Chronic obstructive pulmonary disease | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 1/177 (0.6%) | 1 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||
Drug reaction with eosinophilia and systemic symptoms | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Pustular psoriasis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Angioedema | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 1/9 (11.1%) | 1 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Vascular disorders | ||||||||||||||||||||||||
Aortic aneurysm | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Aortic stenosis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Deep vein thrombosis | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Orthostatic hypotension | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||
Placebo - Treatment Period | Placebo/Ocrelizumab 500 mg - Treatment Period | Ocrelizumab 200 mg - Treatment Period | Ocrelizumab 200 mg/Ocrelizumab 500 mg - Treatment Period | Ocrelizumab 500 mg - Treatment Period | Ocrelizumab 500 mg/Ocrelizumab 500 mg - Treatment Period | Placebo - Safety Follow-up Period | Placebo/Ocrelizumab 500 mg - Safety Follow-up Period | Ocrelizumab 200 mg - Safety Follow-up Period | Ocrelizumab 200 mg/Ocrelizumab 500 Mg-safety Follow-up Period | Ocrelizumab 500 mg - Safety Follow-up Period | Ocrelizumab 500 mg/Ocrelizumab 500 mg -Safety Follow-up Period | |||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 128/207 (61.8%) | 4/10 (40%) | 135/196 (68.9%) | 6/12 (50%) | 144/202 (71.3%) | 3/6 (50%) | 35/187 (18.7%) | 3/9 (33.3%) | 32/177 (18.1%) | 3/11 (27.3%) | 49/185 (26.5%) | 5/6 (83.3%) | ||||||||||||
Blood and lymphatic system disorders | ||||||||||||||||||||||||
Lymphadenopathy | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Neutropenia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Anaemia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 3/177 (1.7%) | 3 | 0/11 (0%) | 0 | 2/185 (1.1%) | 3 | 0/6 (0%) | 0 |
Eye disorders | ||||||||||||||||||||||||
Conjunctivitis | 0/207 (0%) | 0 | 1/10 (10%) | 1 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Gastrointestinal disorders | ||||||||||||||||||||||||
Abdominal hernia | 1/207 (0.5%) | 1 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 1/12 (8.3%) | 1 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Nausea | 24/207 (11.6%) | 24 | 0/10 (0%) | 0 | 16/196 (8.2%) | 16 | 0/12 (0%) | 0 | 22/202 (10.9%) | 22 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Diarrhoea | 14/207 (6.8%) | 14 | 0/10 (0%) | 0 | 7/196 (3.6%) | 7 | 0/12 (0%) | 0 | 14/202 (6.9%) | 14 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 3/177 (1.7%) | 3 | 1/11 (9.1%) | 1 | 3/185 (1.6%) | 3 | 0/6 (0%) | 0 |
Dyspepsia | 14/207 (6.8%) | 14 | 0/10 (0%) | 0 | 8/196 (4.1%) | 8 | 0/12 (0%) | 0 | 13/202 (6.4%) | 13 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Abdominal distension | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Gastric ulcer | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 1/11 (9.1%) | 1 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Gastritis atrophic | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 1/11 (9.1%) | 1 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
General disorders | ||||||||||||||||||||||||
Oedema | 2/207 (1%) | 2 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 1/6 (16.7%) | 1 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Hepatobiliary disorders | ||||||||||||||||||||||||
Drug-induced liver injury | 18/207 (8.7%) | 18 | 0/10 (0%) | 0 | 28/196 (14.3%) | 28 | 0/12 (0%) | 0 | 27/202 (13.4%) | 27 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Infections and infestations | ||||||||||||||||||||||||
Upper respiratory tract infection | 36/207 (17.4%) | 45 | 0/10 (0%) | 0 | 31/196 (15.8%) | 38 | 0/12 (0%) | 0 | 23/202 (11.4%) | 29 | 1/6 (16.7%) | 1 | 7/187 (3.7%) | 7 | 1/9 (11.1%) | 1 | 3/177 (1.7%) | 3 | 2/11 (18.2%) | 3 | 7/185 (3.8%) | 7 | 0/6 (0%) | 0 |
Cystitis | 3/207 (1.4%) | 4 | 0/10 (0%) | 0 | 4/196 (2%) | 6 | 0/12 (0%) | 0 | 4/202 (2%) | 4 | 1/6 (16.7%) | 1 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 1/177 (0.6%) | 1 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Tooth infection | 1/207 (0.5%) | 1 | 1/10 (10%) | 1 | 1/196 (0.5%) | 1 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Bronchitis | 21/207 (10.1%) | 21 | 0/10 (0%) | 0 | 22/196 (11.2%) | 22 | 0/12 (0%) | 0 | 15/202 (7.4%) | 15 | 0/6 (0%) | 0 | 3/187 (1.6%) | 3 | 1/9 (11.1%) | 1 | 5/177 (2.8%) | 5 | 0/11 (0%) | 0 | 3/185 (1.6%) | 5 | 0/6 (0%) | 0 |
Urinary tract infection | 12/207 (5.8%) | 12 | 0/10 (0%) | 0 | 21/196 (10.7%) | 21 | 0/12 (0%) | 0 | 25/202 (12.4%) | 25 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 5/177 (2.8%) | 5 | 0/11 (0%) | 0 | 12/185 (6.5%) | 12 | 0/6 (0%) | 0 |
Nasopharyngitis | 11/207 (5.3%) | 11 | 0/10 (0%) | 0 | 18/196 (9.2%) | 18 | 0/12 (0%) | 0 | 16/202 (7.9%) | 16 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Sinusitis | 10/207 (4.8%) | 10 | 0/10 (0%) | 0 | 7/196 (3.6%) | 7 | 0/12 (0%) | 0 | 15/202 (7.4%) | 15 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Gastroenteritis | 9/207 (4.3%) | 9 | 0/10 (0%) | 0 | 10/196 (5.1%) | 10 | 0/12 (0%) | 0 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Cellulitis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 1/177 (0.6%) | 1 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Influenza | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 2/187 (1.1%) | 2 | 1/9 (11.1%) | 1 | 1/177 (0.6%) | 1 | 1/11 (9.1%) | 1 | 3/185 (1.6%) | 4 | 0/6 (0%) | 0 |
Tinea versicolour | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 2/185 (1.1%) | 2 | 0/6 (0%) | 0 |
Fungal skin infection | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Lower respiratory tract infection | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Sinusitis bacterial | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 1/9 (11.1%) | 1 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||||||||||||||||
Infusion related reaction | 21/207 (10.1%) | 36 | 4/10 (40%) | 4 | 56/196 (28.6%) | 79 | 0/12 (0%) | 0 | 64/202 (31.7%) | 91 | 1/6 (16.7%) | 1 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Meniscus injury | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 2/187 (1.1%) | 2 | 0/9 (0%) | 0 | 1/177 (0.6%) | 1 | 1/11 (9.1%) | 1 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Limb injury | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 1/11 (9.1%) | 1 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Muscle strain | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 1/9 (11.1%) | 1 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Foot fracture | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 1/11 (9.1%) | 1 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Investigations | ||||||||||||||||||||||||
Liver function test abnormal | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 1/12 (8.3%) | 1 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Blood creatine phosphokinase increased | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 1/9 (11.1%) | 1 | 1/177 (0.6%) | 1 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||||||||||||||||
Hyperlipidaemia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Vitamin D deficiency | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 1/6 (16.7%) | 1 |
Dyslipidaemia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 1/177 (0.6%) | 1 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 1/6 (16.7%) | 1 |
Hypocalcaemia | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 1/9 (11.1%) | 1 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
Periarthritis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 1/12 (8.3%) | 1 | 1/202 (0.5%) | 1 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Back pain | 9/207 (4.3%) | 9 | 0/10 (0%) | 0 | 10/196 (5.1%) | 10 | 0/12 (0%) | 0 | 7/202 (3.5%) | 7 | 0/6 (0%) | 0 | 4/187 (2.1%) | 4 | 1/9 (11.1%) | 1 | 2/177 (1.1%) | 2 | 0/11 (0%) | 0 | 6/185 (3.2%) | 7 | 0/6 (0%) | 0 |
Osteoarthritis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 1/177 (0.6%) | 1 | 1/11 (9.1%) | 1 | 2/185 (1.1%) | 2 | 0/6 (0%) | 0 |
Tenosynovitis stenosans | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 1/9 (11.1%) | 1 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||
Thyroid neoplasm | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Nervous system disorders | ||||||||||||||||||||||||
Headache | 13/207 (6.3%) | 13 | 0/10 (0%) | 0 | 12/196 (6.1%) | 12 | 0/12 (0%) | 0 | 7/202 (3.5%) | 7 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Psychiatric disorders | ||||||||||||||||||||||||
Anxiety | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 1/9 (11.1%) | 1 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
Wheezing | 0/207 (0%) | 0 | 1/10 (10%) | 1 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Cough | 0/207 (0%) | 0/10 (0%) | 0/196 (0%) | 0/12 (0%) | 0/202 (0%) | 0/6 (0%) | 2/187 (1.1%) | 2 | 1/9 (11.1%) | 1 | 2/177 (1.1%) | 2 | 0/11 (0%) | 0 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 | ||||||
Sinusitis noninfective | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 1/6 (16.7%) | 1 |
Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||
Dry skin | 2/207 (1%) | 3 | 0/10 (0%) | 0 | 1/196 (0.5%) | 1 | 1/12 (8.3%) | 1 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Erythema | 0/207 (0%) | 0 | 1/10 (10%) | 1 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Rosacea | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 1/12 (8.3%) | 1 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Exfoliative rash | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 1 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Rash | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 1/187 (0.5%) | 1 | 0/9 (0%) | 0 | 2/177 (1.1%) | 2 | 1/11 (9.1%) | 1 | 1/185 (0.5%) | 1 | 0/6 (0%) | 0 |
Dermatitis contact | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 2/187 (1.1%) | 2 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 1/6 (16.7%) | 1 |
Angioedema | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 1/9 (11.1%) | 1 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Onychoclasis | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 1/11 (9.1%) | 1 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Pruritus | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 1/9 (11.1%) | 1 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Surgical and medical procedures | ||||||||||||||||||||||||
Hip arthroplasty | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 1/12 (8.3%) | 2 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Bunion operation | 0/207 (0%) | 0 | 0/10 (0%) | 0 | 0/196 (0%) | 0 | 0/12 (0%) | 0 | 0/202 (0%) | 0 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 1/6 (16.7%) | 1 |
Vascular disorders | ||||||||||||||||||||||||
Hypertension | 23/207 (11.1%) | 23 | 0/10 (0%) | 0 | 14/196 (7.1%) | 14 | 0/12 (0%) | 0 | 18/202 (8.9%) | 18 | 0/6 (0%) | 0 | 0/187 (0%) | 0 | 0/9 (0%) | 0 | 0/177 (0%) | 0 | 0/11 (0%) | 0 | 0/185 (0%) | 0 | 0/6 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title | Medical Communications |
---|---|
Organization | F. Hoffmann-La Roche AG |
Phone | 41 616878333 |
global.trial_information@roche.com |
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