A Study Comparing SB2 to Remicade® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy
Sponsor
Samsung Bioepis Co., Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT01936181
Collaborator
(none)
584
2
4
25
292
11.7
Study Details
Study Description
Brief Summary
This is a randomized, double-blind, parallel group, multicentre clinical study to evaluate the efficacy, safety, pharmacokinetics and immunogenicity of SB2 compared to Remicade in subjects with moderate to severe Rheumatoid Arthritis (RA) despite Methotrexate (MTX) therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
584 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomised, Double-blind, Parallel Group, Multicentre Clinical Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Immunogenicity of SB2 Compared to Remicade® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy
Study Start Date
:
Aug 1, 2013
Actual Primary Completion Date
:
Sep 1, 2014
Actual Study Completion Date
:
Sep 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SB2 (proposed biosimilar to inflixmab) SB2 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 70 |
Drug: SB2 (proposed biosimilar to infliximab)
|
| Active Comparator: Remicade (infliximab) Remicade 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 46 |
Drug: Remicade (infliximab)
|
| Experimental: Remicade (infliximab), switch to SB2 SB2 3mg/kg at week 54, 62, 70 |
Drug: SB2 (proposed biosimilar to infliximab)
|
| Active Comparator: Remicade (infliximab), continue as Remicade Remicade 3mg/kg at week 54, 62, 70 |
Drug: Remicade (infliximab)
|
Outcome Measures
Primary Outcome Measures
- American College of Rheumatology 20% Response Criteria (ACR20) [Week 30]
Secondary Outcome Measures
- ACR20 [Week 54, Week 78]
- American College of Rheumatology 50% Response Criteria (ACR50) [Week 30, Week 54, Week 78]
- Disease Activity Score Based on a 28 Joint Count (DAS28) [Week 30, Week 54, Week 78]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosed as having RA according to the revised 1987 ACR criteria for at least 6 months
-
Have moderate to severe active disease despite MTX therapy defined as having more than or equal to six swollen joints and more than or equal to six tender joints and either erythrocyte sedimentation rate (ESR, Westergren) ≥ 28 mm/h or serum C-reactive protein ≥ 1.0 mg/dL
-
Must have been treated with MTX for at least 6 months prior to Randomisation and on a stable dose of MTX 10-25 mg/week given at least 4 weeks prior to Screening
-
Female subjects who are not pregnant or nursing at Screening and who are not planning to become pregnant from Screening until 6 months after the last dose of investigational product
Inclusion Criteria for Transition-Extension Period:
-
Have been enrolled and completed the scheduled Week 54 visit of the randomised, double-blind period of the SB2-G31-RA study
-
In the opinion of the Investigator, subjects who may benefit from continuing IP treatment (either SB2 or Remicade), understand the implications of taking part in the study and willing to participate in the transition-extension period
Exclusion Criteria:
-
Have been treated previously with any biological agents including any tumour necrosis factor inhibitor
-
Have a known hypersensitivity to human immunoglobulin proteins or other components of Remicade or SB2
-
Have a positive serological test for hepatitis B or hepatitis C or have a known history of infection with human immunodeficiency virus
-
Have a current diagnosis of active tuberculosis
-
Have had a serious infection or have been treated with intravenous antibiotics for an infection within 8 weeks or oral antibiotics within 2 weeks prior to Randomisation.
-
Have any of the following conditions
-
Other inflammatory or rheumatic diseases.
-
History of any malignancy within the previous 5 years prior to Screening
-
History of lymphoproliferative disease including lymphoma.
-
History of congestive heart failure
-
Physical incapacitation (ACR functional Class IV or wheelchair-/bed-bound).
-
History of demyelinating disorders.
Exclusion Criteria for Transition-Extension Period:
-
Have been withdrawn from the SB2-G31-RA study for any reason
-
Have had any significant medical conditions, such as an occurrence of a serious AE (SAE) or intolerance of SB2 or Remicade during the randomised, double-blind period of the SB2-G31-RA study which may render the subject unsuitable to participate in the transition-extension period, at the discretion of the Investigator
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site | Hristo Botev Str. | Sliven | Bulgaria | 8800 |
| 2 | Investigational Site | Santariskiu | Vilnius | Lithuania | 08661 |
Sponsors and Collaborators
- Samsung Bioepis Co., Ltd.
Investigators
- Principal Investigator: Jung-Yoon Choe, M.D., Ph.D., Daegu Catholic University Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Samsung Bioepis Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01936181
Other Study ID Numbers:
- SB2-G31-RA
First Posted:
Sep 5, 2013
Last Update Posted:
Sep 14, 2017
Last Verified:
Aug 1, 2017
Keywords provided by Samsung Bioepis Co., Ltd.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | SB2 (Proposed Biosimilar to Inflixmab) | Remicade (Infliximab) | Remicade (Infliximab), Switch to SB2 | Remicade (Infliximab), Continue as Remicade |
|---|---|---|---|---|
| Arm/Group Description | SB2 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 70 SB2 (proposed biosimilar to infliximab) | Remicade 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 46 At Week 54, subjects were randomised again in a 1:1 ratio to either continue on Remicade (Remicade/Remicade) or be transitioned to SB2 (Remicade/SB2) up to Week 70. | SB2 3mg/kg at week 54, 62, 70 SB2 (proposed biosimilar to infliximab) | Remicade 3mg/kg at week 54, 62, 70 Remicade (infliximab) |
| Period Title: Randomised, Double-blind | ||||
| STARTED | 291 | 293 | 0 | 0 |
| COMPLETED | 227 | 225 | 0 | 0 |
| NOT COMPLETED | 64 | 68 | 0 | 0 |
| Period Title: Randomised, Double-blind | ||||
| STARTED | 201 | 0 | 94 | 101 |
| COMPLETED | 186 | 0 | 88 | 96 |
| NOT COMPLETED | 15 | 0 | 6 | 5 |
Baseline Characteristics
| Arm/Group Title | SB2 (Proposed Biosimilar to Inflixmab) | Remicade (Infliximab) | Total |
|---|---|---|---|
| Arm/Group Description | SB2 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 70 SB2 (proposed biosimilar to infliximab) | Remicade 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 46 At Week 54, subjects were randomised again in a 1:1 ratio to either continue on Remicade (Remicade/Remicade) or be transitioned to SB2 (Remicade/SB2) up to Week 70. | Total of all reporting groups |
| Overall Participants | 291 | 293 | 584 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
51.6
(11.92)
|
52.6
(11.74)
|
52.1
(11.83)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
232
79.7%
|
236
80.5%
|
468
80.1%
|
| Male |
59
20.3%
|
57
19.5%
|
116
19.9%
|
Outcome Measures
| Title | American College of Rheumatology 20% Response Criteria (ACR20) |
|---|---|
| Description | |
| Time Frame | Week 30 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | SB2 (Proposed Biosimilar to Inflixmab) | Remicade (Infliximab) |
|---|---|---|
| Arm/Group Description | SB2 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 70 SB2 (proposed biosimilar to infliximab) | Remicade 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 46 At Week 54, subjects were randomised again in a 1:1 ratio to either continue on Remicade (Remicade/Remicade) or be transitioned to SB2 (Remicade/SB2) up to Week 70. |
| Measure Participants | 231 | 247 |
| Number [percentage of participants] |
64.1
22%
|
66.0
22.5%
|
| Title | ACR20 |
|---|---|
| Description | |
| Time Frame | Week 54, Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | SB2 at Week 54 | Remicade (Infliximab) at Week 54 | SB2 at Week 78 | Remicade (Infliximab), Switch to SB2 at Week 78 | Remicade (Infliximab), Continue as Remicade |
|---|---|---|---|---|---|
| Arm/Group Description | SB2 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 70 SB2 (proposed biosimilar to infliximab) | Remicade 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 46 | SB2 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 70 SB2 (proposed biosimilar to infliximab) | Remicade 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 46 At Week 54, subjects were randomised to be transitioned to SB2 (Remicade/SB2) up to Week 70 and received SB2 3mg/kg at week 54, 62, 70. SB2 (proposed biosimilar to infliximab) | Remicade 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 46 At Week 54, subjects were randomised to continue on Remicade (Remicade/Remicade) up to Week 70 and received Remicade 3mg/kg at week 54, 62, 70. |
| Measure Participants | 202 | 208 | 180 | 85 | 93 |
| Number [percentage of participants] |
65.3
22.4%
|
69.2
23.6%
|
68.3
11.7%
|
63.5
NaN
|
68.8
NaN
|
| Title | American College of Rheumatology 50% Response Criteria (ACR50) |
|---|---|
| Description | |
| Time Frame | Week 30, Week 54, Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Disease Activity Score Based on a 28 Joint Count (DAS28) |
|---|---|
| Description | |
| Time Frame | Week 30, Week 54, Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | SB2 (Proposed Biosimilar to Inflixmab) | Remicade (Infliximab) | ||
| Arm/Group Description | SB2 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 70 SB2 (proposed biosimilar to infliximab) | Remicade 3 mg/kg at week 0, 2, 6 then every 8 weeks thereafter via intravenous infusion up to Week 46 At Week 54, subjects were randomised again in a 1:1 ratio to either continue on Remicade (Remicade/Remicade) or be transitioned to SB2 (Remicade/SB2) up to Week 70. | ||
All Cause Mortality |
||||
| SB2 (Proposed Biosimilar to Inflixmab) | Remicade (Infliximab) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/290 (0%) | 1/293 (0.3%) | ||
Serious Adverse Events |
||||
| SB2 (Proposed Biosimilar to Inflixmab) | Remicade (Infliximab) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 36/290 (12.4%) | 38/293 (13%) | ||
| Blood and lymphatic system disorders | ||||
| Thrombocytosis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Cardiac disorders | ||||
| Angina Unstable | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Atrial Fibrillation | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Myocardial Infarction | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Angina Pectoris | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Left Ventricular Failure | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Pericarditis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Gastrointestinal disorders | ||||
| Diverticulum | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Ileus Paralytic | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Irritable Bowel Syndrome | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Abdominal Wall Haemorrhage | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Ileal Perforation | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Peptic Ulcer Haemorrhage | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Salivary Gland Calculus | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| General disorders | ||||
| Device Damage | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Bile Duct Stone | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Cholecystitis Acute | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Immune system disorders | ||||
| Anaphylactic Reaction | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Hypersensitivity | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Anaphylactic Shock | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Drug Hypersensitivity | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Infections and infestations | ||||
| Pneumonia | 3/290 (1%) | 3 | 2/293 (0.7%) | 2 |
| Appendicitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Bronchitis | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Clostridium Difficile Colitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Pneumonia Bacterial | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Pseudomembranous Colitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Pyelonephritis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Soft Tissue Infection | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Tuberculous Pleurisy | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Urinary Tract Infection | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Urosepsis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Arthritis Bacterial | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Cellulitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Diabetic Foot Infection | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Erysipelas | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Haematoma Infection | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Respiratory Tract Infection | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Wound Infection | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Lower Limb Fracture | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Lumbar Vertebral Fracture | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Periprosthetic Fracture | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Rib Fracture | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Thoracic Vertebral Fracture | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Tibia Fracture | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Rheumatoid Arthritis | 4/290 (1.4%) | 4 | 4/293 (1.4%) | 4 |
| Foot Deformity | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Fistula | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Intervertebral Disc Protrusion | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Joint Swelling | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Osteoarthritis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Synovitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Benign Lung Neoplasm | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Brain Neoplasm | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Breast Cancer | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Prostate Cancer | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Basal Cell Carcinoma | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Benign Salivary Gland Neoplasm | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Lip And/Or Oral Cavity Cancer | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Nervous system disorders | ||||
| Sciatica | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Vertebrobasilar Insufficiency | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Neuropathy Peripheral | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Psychiatric disorders | ||||
| Major Depression | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Psychotic Disorder | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Reproductive system and breast disorders | ||||
| Benign Prostatic Hyperplasia | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Endometriosis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Ovarian Cyst Torsion | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Pleurisy | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Urticaria | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| SB2 (Proposed Biosimilar to Inflixmab) | Remicade (Infliximab) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 201/290 (69.3%) | 203/293 (69.3%) | ||
| Blood and lymphatic system disorders | ||||
| Leukopenia | 4/290 (1.4%) | 5 | 4/293 (1.4%) | 4 |
| Anaemia | 3/290 (1%) | 3 | 2/293 (0.7%) | 2 |
| Lymphopenia | 3/290 (1%) | 4 | 2/293 (0.7%) | 2 |
| Eosinophilia | 2/290 (0.7%) | 2 | 1/293 (0.3%) | 1 |
| Neutropenia | 2/290 (0.7%) | 2 | 3/293 (1%) | 4 |
| Thrombocytosis | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Anaemia Of Chronic Disease | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Leukocytosis | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Lymphadenitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Lymphadenopathy | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Thrombocytopenia | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Iron Deficiency Anaemia | 0/290 (0%) | 0 | 4/293 (1.4%) | 5 |
| Cardiac disorders | ||||
| Coronary Artery Disease | 2/290 (0.7%) | 2 | 1/293 (0.3%) | 1 |
| Palpitations | 2/290 (0.7%) | 2 | 1/293 (0.3%) | 1 |
| Angina Unstable | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Atrial Fibrillation | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Hypertensive Cardiomyopathy | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Myocardial Infarction | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Ventricular Extrasystoles | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Angina Pectoris | 0/290 (0%) | 0 | 2/293 (0.7%) | 3 |
| Left Ventricular Failure | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Pericarditis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Tachycardia | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Ear and labyrinth disorders | ||||
| Cerumen Impaction | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Hypoacusis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Vertigo | 1/290 (0.3%) | 1 | 2/293 (0.7%) | 2 |
| Hearing Impaired | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Tinnitus | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Endocrine disorders | ||||
| Goitre | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Hypothyroidism | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Eye disorders | ||||
| Cataract | 3/290 (1%) | 3 | 0/293 (0%) | 0 |
| Conjunctivitis | 2/290 (0.7%) | 2 | 6/293 (2%) | 6 |
| Eye Pruritus | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Dry Eye | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Eyelid Exfoliation | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Eyelid Oedema | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Keratitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Lacrimation Increased | 1/290 (0.3%) | 2 | 0/293 (0%) | 0 |
| Myopia | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Ocular Hyperaemia | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Presbyopia | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Retinopathy Hypertensive | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Visual Impairment | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Chorioretinopathy | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Conjunctival Haemorrhage | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Erythema Of Eyelid | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Gastrointestinal disorders | ||||
| Nausea | 6/290 (2.1%) | 6 | 4/293 (1.4%) | 4 |
| Abdominal Pain Upper | 5/290 (1.7%) | 7 | 6/293 (2%) | 6 |
| Abdominal Pain | 3/290 (1%) | 4 | 3/293 (1%) | 3 |
| Gastrooesophageal Reflux Disease | 3/290 (1%) | 3 | 4/293 (1.4%) | 4 |
| Toothache | 3/290 (1%) | 4 | 0/293 (0%) | 0 |
| Abdominal Distension | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Constipation | 2/290 (0.7%) | 2 | 2/293 (0.7%) | 3 |
| Enterocolitis | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Gastritis Erosive | 2/290 (0.7%) | 2 | 2/293 (0.7%) | 2 |
| Vomiting | 2/290 (0.7%) | 2 | 3/293 (1%) | 3 |
| Dental Caries | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Diarrhoea | 1/290 (0.3%) | 1 | 4/293 (1.4%) | 4 |
| Diverticulum | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Dyspepsia | 1/290 (0.3%) | 3 | 7/293 (2.4%) | 7 |
| Epigastric Discomfort | 1/290 (0.3%) | 2 | 1/293 (0.3%) | 1 |
| Food Poisoning | 1/290 (0.3%) | 2 | 0/293 (0%) | 0 |
| Gastric Polyps | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Gastritis | 1/290 (0.3%) | 1 | 3/293 (1%) | 3 |
| Glossodynia | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Haemorrhoidal Haemorrhage | 1/290 (0.3%) | 2 | 0/293 (0%) | 0 |
| Ileus Paralytic | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Irritable Bowel Syndrome | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Pancreatitis Acute | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Submaxillary Gland Enlargement | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Abdominal Discomfort | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Abdominal Wall Haemorrhage | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Aphthous Stomatitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Duodenal Ulcer | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Duodenitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Enteritis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Gastritis Atrophic | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Gastroduodenitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Gastrointestinal Inflammation | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Gastrointestinal Ischaemia | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Gastrointestinal Pain | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Hiatus Hernia | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Ileal Perforation | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Large Intestine Polyp | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Oesophagitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Oral Pain | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Peptic Ulcer Haemorrhage | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Salivary Gland Calculus | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| General disorders | ||||
| Fatigue | 4/290 (1.4%) | 4 | 1/293 (0.3%) | 1 |
| Chest Discomfort | 3/290 (1%) | 3 | 0/293 (0%) | 0 |
| Chest Pain | 3/290 (1%) | 7 | 1/293 (0.3%) | 1 |
| Chills | 3/290 (1%) | 3 | 3/293 (1%) | 5 |
| Oedema Peripheral | 3/290 (1%) | 3 | 4/293 (1.4%) | 4 |
| Pyrexia | 3/290 (1%) | 3 | 9/293 (3.1%) | 11 |
| Spinal Pain | 2/290 (0.7%) | 2 | 1/293 (0.3%) | 1 |
| Asthenia | 1/290 (0.3%) | 1 | 2/293 (0.7%) | 2 |
| Device Damage | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Face Oedema | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Influenza Like Illness | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Injection Site Hypersensitivity | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Injection Site Pruritus | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Local Swelling | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Malaise | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Nodule | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Thirst | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Feeling Cold | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Hernia | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Impaired Healing | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Injection Site Rash | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Irritability | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Pain | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Hepatobiliary disorders | ||||
| Bile Duct Stone | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Biliary Colic | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Cholecystitis Acute | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Cholecystitis Chronic | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Hepatitis Toxic | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Liver Disorder | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Cholelithiasis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Drug-Induced Liver Injury | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Hepatic Pain | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Hepatic Steatosis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Hyperbilirubinaemia | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Immune system disorders | ||||
| Hypersensitivity | 3/290 (1%) | 3 | 3/293 (1%) | 3 |
| Allergy To Arthropod Sting | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Anaphylactic Reaction | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Anaphylactic Shock | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Drug Hypersensitivity | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Food Allergy | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Infections and infestations | ||||
| Nasopharyngitis | 26/290 (9%) | 34 | 25/293 (8.5%) | 34 |
| Latent Tuberculosis | 24/290 (8.3%) | 31 | 27/293 (9.2%) | 33 |
| Bronchitis | 13/290 (4.5%) | 15 | 15/293 (5.1%) | 18 |
| Upper Respiratory Tract Infection | 13/290 (4.5%) | 15 | 18/293 (6.1%) | 31 |
| Urinary Tract Infection | 8/290 (2.8%) | 8 | 7/293 (2.4%) | 7 |
| Pneumonia | 7/290 (2.4%) | 7 | 8/293 (2.7%) | 8 |
| Pharyngitis | 6/290 (2.1%) | 7 | 9/293 (3.1%) | 12 |
| Cystitis | 3/290 (1%) | 3 | 4/293 (1.4%) | 4 |
| Herpes Zoster | 3/290 (1%) | 3 | 2/293 (0.7%) | 2 |
| Influenza | 3/290 (1%) | 3 | 4/293 (1.4%) | 6 |
| Respiratory Tract Infection | 3/290 (1%) | 3 | 2/293 (0.7%) | 2 |
| Rhinitis | 3/290 (1%) | 3 | 5/293 (1.7%) | 5 |
| Sinusitis | 3/290 (1%) | 3 | 1/293 (0.3%) | 1 |
| Herpes Virus Infection | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Oral Herpes | 2/290 (0.7%) | 3 | 3/293 (1%) | 6 |
| Periodontitis | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Pulpitis Dental | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Acute Tonsillitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Appendicitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Clostridium Difficile Colitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Laryngitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Onychomycosis | 1/290 (0.3%) | 2 | 2/293 (0.7%) | 2 |
| Paronychia | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Parotitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Pneumonia Bacterial | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Pseudomembranous Colitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Pyelonephritis | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Pyelonephritis Chronic | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Schistosomiasis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Soft Tissue Infection | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Tonsillitis | 1/290 (0.3%) | 1 | 7/293 (2.4%) | 13 |
| Tooth Abscess | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Tuberculous Pleurisy | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Urosepsis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Viral Infection | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Viral Upper Respiratory Tract Infection | 1/290 (0.3%) | 1 | 5/293 (1.7%) | 6 |
| Abscess Limb | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Arthritis Bacterial | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Atypical Mycobacterial Pneumonia | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Cellulitis | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Dacryocystitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Diabetic Foot Infection | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Ear Infection | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Erysipelas | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Furuncle | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Gastroenteritis | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Gingivitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Haematoma Infection | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Lyme Disease | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Osteomyelitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Otitis Media | 0/290 (0%) | 0 | 3/293 (1%) | 4 |
| Otitis Media Acute | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Peritonitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Pharyngitis Bacterial | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Pulmonary Tuberculosis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Rash Pustular | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Respiratory Tract Infection Viral | 0/290 (0%) | 0 | 3/293 (1%) | 3 |
| Sepsis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Sialoadenitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Subcutaneous Abscess | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Tracheitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Vaginal Infection | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Wound Infection | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Infusion Related Reaction | 3/290 (1%) | 3 | 5/293 (1.7%) | 5 |
| Ankle Fracture | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Fall | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Humerus Fracture | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Joint Injury | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Lower Limb Fracture | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Muscle Rupture | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Post Procedural Complication | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Postoperative Wound Complication | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Stab Wound | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Tendon Rupture | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Thermal Burn | 1/290 (0.3%) | 2 | 0/293 (0%) | 0 |
| Upper Limb Fracture | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Wrist Fracture | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Arthropod Bite | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Epicondylitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Forearm Fracture | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Joint Dislocation | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Laceration | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Ligament Sprain | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Lumbar Vertebral Fracture | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Periprosthetic Fracture | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Radius Fracture | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Rib Fracture | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Subcutaneous Haematoma | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Thoracic Vertebral Fracture | 0/290 (0%) | 0 | 3/293 (1%) | 3 |
| Tibia Fracture | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Investigations | ||||
| Alanine Aminotransferase Increased | 27/290 (9.3%) | 32 | 14/293 (4.8%) | 15 |
| Aspartate Aminotransferase Increased | 16/290 (5.5%) | 18 | 15/293 (5.1%) | 15 |
| Lymphocyte Count Decreased | 7/290 (2.4%) | 8 | 2/293 (0.7%) | 3 |
| Gamma-Glutamyltransferase Increased | 5/290 (1.7%) | 5 | 4/293 (1.4%) | 4 |
| Neutrophil Count Increased | 4/290 (1.4%) | 5 | 0/293 (0%) | 0 |
| Blood Creatinine Increased | 3/290 (1%) | 3 | 2/293 (0.7%) | 2 |
| Blood Pressure Increased | 3/290 (1%) | 3 | 1/293 (0.3%) | 1 |
| Blood Alkaline Phosphatase Increased | 2/290 (0.7%) | 2 | 1/293 (0.3%) | 1 |
| Blood Bilirubin Increased | 2/290 (0.7%) | 2 | 1/293 (0.3%) | 2 |
| Haemoglobin Decreased | 2/290 (0.7%) | 2 | 1/293 (0.3%) | 1 |
| Neutrophil Count Decreased | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Transaminases Increased | 2/290 (0.7%) | 3 | 0/293 (0%) | 0 |
| White Blood Cell Count Decreased | 2/290 (0.7%) | 5 | 2/293 (0.7%) | 4 |
| Aspiration Joint | 1/290 (0.3%) | 2 | 0/293 (0%) | 0 |
| Blood Calcium Increased | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Blood Glucose Increased | 1/290 (0.3%) | 1 | 4/293 (1.4%) | 4 |
| Blood Phosphorus Decreased | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| C-Reactive Protein Increased | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Glucose Urine | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Granulocyte Count Decreased | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| International Normalised Ratio Decreased | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| International Normalised Ratio Increased | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Lymphocyte Count Increased | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Platelet Count Decreased | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Vitamin B12 Decreased | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| White Blood Cell Count Increased | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Alanine Aminotransferase Abnormal | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Antinuclear Antibody Increased | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Antinuclear Antibody Positive | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Blood Cholesterol Increased | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Blood Potassium Increased | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Body Temperature Increased | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Double Stranded Dna Antibody | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Electrocardiogram Abnormal | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Haematocrit Decreased | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Haematology Test Abnormal | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Hepatic Enzyme Increased | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Liver Function Test Abnormal | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Red Blood Cell Count Decreased | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Red Blood Cell Sedimentation Rate Increased | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Weight Decreased | 0/290 (0%) | 0 | 2/293 (0.7%) | 3 |
| Weight Increased | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Metabolism and nutrition disorders | ||||
| Hyperlipidaemia | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Type 2 Diabetes Mellitus | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Diabetes Mellitus | 1/290 (0.3%) | 1 | 2/293 (0.7%) | 2 |
| Dyslipidaemia | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Gout | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Hyperglycaemia | 1/290 (0.3%) | 1 | 2/293 (0.7%) | 2 |
| Hyperkalaemia | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Hypokalaemia | 1/290 (0.3%) | 2 | 0/293 (0%) | 0 |
| Hyponatraemia | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Hypophosphataemia | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Obesity | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Hypercholesterolaemia | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Rheumatoid Arthritis | 24/290 (8.3%) | 30 | 15/293 (5.1%) | 20 |
| Arthralgia | 8/290 (2.8%) | 9 | 9/293 (3.1%) | 11 |
| Back Pain | 8/290 (2.8%) | 8 | 14/293 (4.8%) | 16 |
| Pain In Extremity | 5/290 (1.7%) | 6 | 0/293 (0%) | 0 |
| Musculoskeletal Pain | 3/290 (1%) | 5 | 3/293 (1%) | 3 |
| Osteoarthritis | 3/290 (1%) | 3 | 3/293 (1%) | 4 |
| Arthritis | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Muscle Spasms | 2/290 (0.7%) | 2 | 3/293 (1%) | 11 |
| Foot Deformity | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Intervertebral Disc Disorder | 1/290 (0.3%) | 11 | 0/293 (0%) | 0 |
| Joint Swelling | 1/290 (0.3%) | 1 | 4/293 (1.4%) | 4 |
| Lupus-Like Syndrome | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Muscle Contracture | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 2 |
| Musculoskeletal Stiffness | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Myalgia | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Neck Pain | 1/290 (0.3%) | 2 | 2/293 (0.7%) | 2 |
| Osteitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Osteoporosis | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Osteoporotic Fracture | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Rheumatoid Nodule | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Scoliosis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Spinal Osteoarthritis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Fistula | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Intervertebral Disc Protrusion | 0/290 (0%) | 0 | 3/293 (1%) | 4 |
| Ligament Disorder | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Muscular Weakness | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Musculoskeletal Chest Pain | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Musculoskeletal Discomfort | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Osteopenia | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Osteoporosis Postmenopausal | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Synovitis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Benign Lung Neoplasm | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Brain Neoplasm | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Breast Cancer | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Eye Naevus | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Gastrointestinal Submucosal Tumour | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Haemangioma Of Liver | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Prostate Cancer | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Thyroid Neoplasm | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Basal Cell Carcinoma | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Benign Neoplasm Of Thyroid Gland | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Benign Salivary Gland Neoplasm | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Colon Adenoma | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Lip And/Or Oral Cavity Cancer | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Papillary Thyroid Cancer | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Nervous system disorders | ||||
| Headache | 16/290 (5.5%) | 30 | 15/293 (5.1%) | 16 |
| Dizziness | 3/290 (1%) | 4 | 7/293 (2.4%) | 11 |
| Cerebrovascular Insufficiency | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Demyelination | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Formication | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Hypertensive Encephalopathy | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Hypoaesthesia | 1/290 (0.3%) | 2 | 1/293 (0.3%) | 1 |
| Intercostal Neuralgia | 1/290 (0.3%) | 2 | 0/293 (0%) | 0 |
| Migraine | 1/290 (0.3%) | 4 | 1/293 (0.3%) | 1 |
| Neuralgia | 1/290 (0.3%) | 1 | 3/293 (1%) | 5 |
| Paraesthesia | 1/290 (0.3%) | 2 | 4/293 (1.4%) | 4 |
| Sciatica | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Sinus Headache | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Somnolence | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Syncope | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Trigeminal Neuralgia | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Vertebrobasilar Insufficiency | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Aphasia | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Burning Sensation | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Cerebral Atrophy | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Cerebral Ischaemia | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Loss Of Consciousness | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Neuropathy Peripheral | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Radiculopathy | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Tension Headache | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Psychiatric disorders | ||||
| Insomnia | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Sleep Disorder | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Anxiety | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Anxiety Disorder | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Major Depression | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Neurosis | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Panic Attack | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Psychotic Disorder | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Renal and urinary disorders | ||||
| Pollakiuria | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Dysuria | 1/290 (0.3%) | 2 | 0/293 (0%) | 0 |
| Renal Colic | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Renal Failure Acute | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Reproductive system and breast disorders | ||||
| Benign Prostatic Hyperplasia | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Endometriosis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Breast Cyst | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Breast Mass | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Menopausal Symptoms | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Menorrhagia | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Oligomenorrhoea | 0/290 (0%) | 0 | 1/293 (0.3%) | 2 |
| Ovarian Cyst Torsion | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Vaginal Discharge | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Vaginal Haemorrhage | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Vaginal Inflammation | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 7/290 (2.4%) | 8 | 9/293 (3.1%) | 9 |
| Productive Cough | 3/290 (1%) | 4 | 2/293 (0.7%) | 2 |
| Oropharyngeal Pain | 2/290 (0.7%) | 2 | 2/293 (0.7%) | 6 |
| Rhinitis Allergic | 2/290 (0.7%) | 2 | 0/293 (0%) | 0 |
| Asthma | 1/290 (0.3%) | 1 | 2/293 (0.7%) | 2 |
| Bronchial Obstruction | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Bronchospasm | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Dyspnoea Exertional | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Epistaxis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Nasal Congestion | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Rhinorrhoea | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Atelectasis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Bronchitis Chronic | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Dyspnoea | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Nasal Septum Deviation | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Pharyngeal Erythema | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Pleurisy | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Upper Respiratory Tract Inflammation | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Vocal Cord Thickening | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 7/290 (2.4%) | 8 | 7/293 (2.4%) | 8 |
| Alopecia | 2/290 (0.7%) | 2 | 2/293 (0.7%) | 2 |
| Dyshidrotic Eczema | 2/290 (0.7%) | 2 | 1/293 (0.3%) | 1 |
| Hyperhidrosis | 2/290 (0.7%) | 2 | 1/293 (0.3%) | 1 |
| Psoriasis | 2/290 (0.7%) | 2 | 2/293 (0.7%) | 2 |
| Acne | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Angioedema | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Blister | 1/290 (0.3%) | 4 | 0/293 (0%) | 0 |
| Dermatitis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Dermatitis Allergic | 1/290 (0.3%) | 1 | 5/293 (1.7%) | 5 |
| Dry Skin | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Eczema | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Erythema Nodosum | 1/290 (0.3%) | 2 | 0/293 (0%) | 0 |
| Pityriasis | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Pruritus | 1/290 (0.3%) | 2 | 5/293 (1.7%) | 6 |
| Pruritus Allergic | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Pruritus Generalised | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Pustular Psoriasis | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 2 |
| Rash Erythematous | 1/290 (0.3%) | 10 | 0/293 (0%) | 0 |
| Rash Papular | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Rash Pruritic | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Skin Exfoliation | 1/290 (0.3%) | 3 | 1/293 (0.3%) | 1 |
| Skin Swelling | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Urticaria | 1/290 (0.3%) | 1 | 3/293 (1%) | 3 |
| Dermatitis Exfoliative | 0/290 (0%) | 0 | 1/293 (0.3%) | 3 |
| Erythema | 0/290 (0%) | 0 | 3/293 (1%) | 5 |
| Ingrowing Nail | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Lichenoid Keratosis | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Pigmentation Disorder | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Pityriasis Rosea | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Rash Generalised | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Rash Macular | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Rash Maculo-Papular | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Rosacea | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Skin Irritation | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Skin Lesion | 0/290 (0%) | 0 | 2/293 (0.7%) | 3 |
| Swelling Face | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Surgical and medical procedures | ||||
| Tooth Extraction | 0/290 (0%) | 0 | 3/293 (1%) | 3 |
| Vascular disorders | ||||
| Hypertension | 8/290 (2.8%) | 8 | 10/293 (3.4%) | 11 |
| Aortic Arteriosclerosis | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Blood Pressure Fluctuation | 1/290 (0.3%) | 1 | 0/293 (0%) | 0 |
| Flushing | 1/290 (0.3%) | 3 | 1/293 (0.3%) | 1 |
| Hot Flush | 1/290 (0.3%) | 1 | 1/293 (0.3%) | 1 |
| Hypertensive Crisis | 1/290 (0.3%) | 1 | 2/293 (0.7%) | 2 |
| Hypotension | 0/290 (0%) | 0 | 2/293 (0.7%) | 2 |
| Raynaud'S Phenomenon | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Varicose Vein | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
| Venous Insufficiency | 0/290 (0%) | 0 | 1/293 (0.3%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
At least sixty (60) days prior to submitting or presenting a manuscript or other materials relating to the Study to a publisher, reviewer, or other outside persons, the Site shall provide to Sponsor a copy of all such manuscripts and materials, and allow Sponsor sixty (60) days to review and comment on them. If the Sponsor requests, the Site shall remove any Confidential Information (other than Study results) prior to submitting or presenting the materials.
Results Point of Contact
| Name/Title | Director, Clinical Development |
|---|---|
| Organization | Samsung Bioepis |
| Phone | +82 31 8061 4534 |
Responsible Party:
Samsung Bioepis Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01936181
Other Study ID Numbers:
- SB2-G31-RA
First Posted:
Sep 5, 2013
Last Update Posted:
Sep 14, 2017
Last Verified:
Aug 1, 2017