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EMBODY4: Open Label Extension Study of Epratuzumab in Subjects With Systemic Lupus Erythematosus

Sponsor
UCB Pharma (Industry)
Overall Status
Completed
CT.gov ID
NCT01408576
Collaborator
(none)
1,250
Enrollment
228
Locations
2
Arms
55.1
Duration (Months)
5.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of the study is assess the safety and tolerability of long-term epratuzumab treatment in subjects with Systemic Lupus Erythematosus (SLE)

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Treatment period was extended by 2 years to a total of 4 years and an amendment was prepared accordingly.

Study Design

Study Type:
Interventional
Actual Enrollment :
1250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Multicenter, Open-label, Extension Study to Assess the Safety and Tolerability of Epratuzumab Treatment in Systemic Lupus Erythematosus Subjects
Study Start Date :
Jul 1, 2011
Actual Primary Completion Date :
Feb 1, 2016
Actual Study Completion Date :
Feb 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Epratuzumab 600 mg per week

600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles

Drug: Epratuzumab
600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over eight 12-week treatment cycles
Experimental: Epratuzumab 1200 mg every other week

1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles

Drug: Epratuzumab
1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over eight 12 week treatment cycles

Outcome Measures

Primary Outcome Measures

  1. Number of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) [During the treatment period (through Week 96)]

    A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.

  2. Percentage of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks) [During the treatment period (through Week 96)]

    A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.

  3. Number of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) [During the treatment period (through Week 96)]

    A SAE is a treatment-emergent adverse event (TEAE) that the investigator classifies as serious. This includes: Death Life-threatening Significant or persistent disability/incapacity Congenital anomaly/birth defect (including that occurring in a fetus) Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or subject and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious Initial inpatient hospitalization or prolongation of hospitalization

  4. Percentage of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks) [During the treatment period (through Week 96)]

    A SAE is a treatment-emergent adverse event (TEAE) that the investigator classifies as serious. This includes: Death Life-threatening Significant or persistent disability/incapacity Congenital anomaly/birth defect (including that occurring in a fetus) Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or subject and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious Initial inpatient hospitalization or prolongation of hospitalization

Secondary Outcome Measures

  1. Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index [At Week 48]

    Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials.

  2. Percentage of Subjects Meeting Treatment Response Criteria According to a Combined Response Index [Week 48]

    Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials.

  3. Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index [Week 96]

    Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials.

  4. The Percent of Subjects Meeting Treatment Response Criteria According to a Combined Response Index [Week 96]

    Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Subject has completed the double-blind study SL0009 (NCT01262365) or SL0010 (NCT01261793) or terminated prematurely at Week 16 or later in SL0009 or SL0010 due to lack of efficacy and would, in the opinion of the investigator, continue to benefit from continued epratuzumab treatment

  • Subject has completed open-label study SL0006 (NCT00383513) or SL0008 (NCT00660881), and would, in the opinion of the investigator, continue to benefit from continued epratuzumab treatment

  • Women of childbearing potential must agree to use an acceptable method of birth control

Exclusion Criteria:

  • Subjects with active, severe, neuropsychiatric SLE, defined as any neuropsychiatric element scoring British Isles Lupus Assessment Group Index (BILAG) level A disease

  • Subjects with active, severe SLE disease activity which involves the renal system

  • Subjects with concurrent relevant medical conditions like defined chronic infections or high risk of new significant infections

  • Substance abuse or dependence

  • History of malignant cancer

  • Subjects with any other condition which, in the investigator's judgment, would make the subject unsuitable for inclusion

Contacts and Locations

Locations

Site City State Country Postal Code
1 539 Birmingham Alabama United States
2 557 Little Rock Arkansas United States
3 515 Hemet California United States
4 544 Huntington Beach California United States
5 550 La Jolla California United States
6 031 Los Angeles California United States
7 051 Los Angeles California United States
8 089 Los Angeles California United States
9 531 San Leandro California United States
10 594 Thousand Oaks California United States
11 558 Torrance California United States
12 048 Aurora Colorado United States
13 037 Colorado Springs Colorado United States
14 532 Denver Colorado United States
15 511 Bridgeport Connecticut United States
16 039 Farmington Connecticut United States
17 042 Aventura Florida United States
18 514 Brandon Florida United States
19 090 Clearwater Florida United States
20 092 DeBary Florida United States
21 533 Fort Lauderdale Florida United States
22 064 Jupiter Florida United States
23 070 Ormond Beach Florida United States
24 084 Palm Harbor Florida United States
25 518 Plantation Florida United States
26 585 Port Orange Florida United States
27 050 Tampa Florida United States
28 538 Tampa Florida United States
29 087 Vero Beach Florida United States
30 537 Atlanta Georgia United States
31 044 Duluth Georgia United States
32 590 Idaho Falls Idaho United States
33 052 Chicago Illinois United States
34 096 Indianapolis Indiana United States
35 060 Shreveport Louisiana United States
36 513 Lansing Michigan United States
37 599 Lansing Michigan United States
38 047 Saint Clair Shores Michigan United States
39 575 Florissant Missouri United States
40 549 Saint Louis Missouri United States
41 596 Nashua New Hampshire United States
42 568 Freehold New Jersey United States
43 593 Trenton New Jersey United States
44 067 Las Cruces New Mexico United States
45 551 Brooklyn New York United States
46 553 Great Neck New York United States
47 545 Manhasset New York United States
48 053 New York New York United States
49 577 Roslyn New York United States
50 077 Charlotte North Carolina United States
51 559 Charlotte North Carolina United States
52 058 Durham North Carolina United States
53 075 Wilmington North Carolina United States
54 061 Columbus Ohio United States
55 071 Middleburg Heights Ohio United States
56 041 Oklahoma City Oklahoma United States
57 076 Oklahoma City Oklahoma United States
58 097 Oklahoma City Oklahoma United States
59 547 Tulsa Oklahoma United States
60 032 Duncansville Pennsylvania United States
61 093 Philadelphia Pennsylvania United States
62 073 Pittsburgh Pennsylvania United States
63 094 Pittsburgh Pennsylvania United States
64 535 Charleston South Carolina United States
65 598 Myrtle Beach South Carolina United States
66 571 Jackson Tennessee United States
67 057 Memphis Tennessee United States
68 574 Amarillo Texas United States
69 078 Austin Texas United States
70 098 Austin Texas United States
71 570 Austin Texas United States
72 079 Dallas Texas United States
73 541 Houston Texas United States
74 563 Houston Texas United States
75 036 Mesquite Texas United States
76 066 San Antonio Texas United States
77 562 San Antonio Texas United States
78 534 Seattle Washington United States
79 429 Camperdown Australia
80 427 Clayton Australia
81 430 Liverpool Australia
82 425 Malvern Australia
83 426 Maroochydore Australia
84 106 Brussels Belgium
85 107 Brussels Belgium
86 105 Leuven Belgium
87 104 Liege Belgium
88 954 Belo Horizonte Brazil
89 956 Campinas Brazil
90 955 Goiânia Brazil
91 950 Juiz de Fora Brazil
92 453 Porto Alegre Brazil
93 451 Recife Brazil
94 450 Rio de Janeiro Brazil
95 952 Rio de Janeiro Brazil
96 452 Salvador Brazil
97 454 Sao Paulo Brazil
98 200 Sofia Bulgaria
99 202 Sofia Bulgaria
100 203 Sofia Bulgaria
101 204 Sofia Bulgaria
102 205 Sofia Bulgaria
103 500 London Ontario Canada
104 502 Hamilton Canada
105 507 Mississauga Canada
106 508 Rimouski Canada
107 506 St. John's Canada
108 504 Toronto Canada
109 218 Olomouc Czechia
110 216 Praha 2 Czechia
111 215 Zlin Czechia
112 226 Tallinn Estonia
113 113 Lille Cedex France
114 618 Limoges Cedex France
115 617 Montpellier Cedex 5 France
116 614 Paris France
117 116 Pessac France
118 616 Toulouse Cedex 9 France
119 127 Berlin Germany
120 628 Berlin Germany
121 633 Berlin Germany
122 128 Frankfurt Germany
123 126 Freiburg Germany
124 637 Hamburg Germany
125 632 Herne Germany
126 625 Koln Germany
127 626 Leipzig Germany
128 634 Mainz Germany
129 627 Munster Germany
130 129 Plochingen Germany
131 636 Roßlau Germany
132 631 Zerbst Germany
133 349 Shatin Hong Kong
134 712 Budapest Hungary
135 716 Budapest Hungary
136 718 Budapest Hungary
137 717 Debrecen Hungary
138 711 Szeged Hungary
139 715 Szeged Hungary
140 713 Zalaegerszeg Hungary
141 378 Ashkelon Israel
142 376 Beer Sheva Israel
143 375 Haifa Israel
144 377 Haifa Israel
145 381 Jerusalem Israel
146 382 Kfar Saba Israel
147 380 Rehovot Israel
148 379 Tel Aviv Israel
149 383 Tel-Hashomer Israel
150 149 Ferrara Italy
151 648 Milano Italy
152 148 Padova Italy
153 647 Pisa Italy
154 646 Roma Italy
155 147 Torino Italy
156 306 Busan Korea, Republic of
157 303 Daegu Korea, Republic of
158 308 Daejeon Korea, Republic of
159 301 Incheon Korea, Republic of
160 307 Seoul Korea, Republic of
161 302 Suwon Korea, Republic of
162 242 Kaunas Lithuania
163 244 Klaipeda Lithuania
164 243 Vilnius Lithuania
165 478 Guadalajara Mexico
166 480 Merida Mexico
167 976 Mexico City Mexico
168 982 Mexico City Mexico
169 981 Torreon Mexico
170 743 Bydgoszcz Poland
171 744 Czestochowa Poland
172 752 Elblag Poland
173 754 Elbląg Poland
174 746 Katowice Poland
175 748 Lublin Poland
176 750 Lublin Poland
177 742 Poznan Poland
178 747 Szczecin Poland
179 751 Ustron Poland
180 749 Warsaw Poland
181 263 Brasov Romania
182 260 Bucharest Romania
183 262 Bucharest Romania
184 264 Bucharest Romania
185 757 Bucharest Romania
186 758 Bucharest Romania
187 261 Cluj-Napoca Romania
188 759 Constanta Romania
189 756 Galati Romania
190 761 Iasi Romania
191 281 Ekaterinburg Russian Federation
192 779 Moscow Russian Federation
193 285 Petrozavodsk Russian Federation
194 284 Saint Petersburg Russian Federation
195 901 Cape Town South Africa
196 902 Durban South Africa
197 903 Stellenbosch South Africa
198 161 Barcelona Spain
199 661 Barcelona Spain
200 164 Bilbao Spain
201 660 Getafe Spain
202 165 La Laguna Spain
203 662 Las Palmas de Gran Canaria Spain
204 162 Madrid Spain
205 163 Madrid Spain
206 664 Madrid Spain
207 166 Malaga Spain
208 177 Santander Spain
209 663 Santiago de Compostela Spain
210 160 Sevilla Spain
211 659 Vigo Spain
212 325 Changhua Taiwan
213 326 Chiayi City Taiwan
214 328 Kaohsiung City Taiwan
215 330 Taipei Taiwan
216 791 Donetsk Ukraine
217 799 Ivano-Frankivsk Ukraine
218 790 Kiev Ukraine
219 794 Kiev Ukraine
220 797 Kiev Ukraine
221 792 Lugansk Ukraine
222 793 Odessa Ukraine
223 796 Vinnytsya Ukraine
224 677 Birmingham United Kingdom
225 178 Brighton United Kingdom
226 182 Doncaster United Kingdom
227 179 Leeds United Kingdom
228 181 Romford United Kingdom

Sponsors and Collaborators

  • UCB Pharma

Investigators

  • Study Director: UCB Clinical Trial Call Center, UCB Pharma

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
UCB Pharma
ClinicalTrials.gov Identifier:
NCT01408576
Other Study ID Numbers:
  • SL0012
  • 2010-020859-30
First Posted:
Aug 3, 2011
Last Update Posted:
Oct 3, 2018
Last Verified:
Mar 1, 2016
Keywords provided by UCB Pharma
Lupus
Monoclonal antibody
B-Cell immunotherapy
Epratuzumab
Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Epratuzumab

Study Results

Participant Flow

Recruitment Details The study started to enroll patients in July 2011 and concluded in February 2016.
Pre-assignment Detail Participant Flow refers to the Enrolled Set, that consisted of all subjects who gave informed consent.
Arm/Group Title Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES)
Arm/Group Description Enrolled Set (ES) of subjects enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Enrolled Set (ES) of subjects enrolled prior to the approval of Protocol Amendment 2 1200 mg infusions delivered every other week (Q2W) for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles Enrolled Set (ES) of subjects enrolled prior to the approval of Protocol Amendment 2 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles
Period Title: Overall Study
STARTED 244 498 508
COMPLETED 56 0 0
NOT COMPLETED 188 498 508

Baseline Characteristics

Arm/Group Title Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES) Total Title
Arm/Group Description Enrolled Set (ES) of subjects enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Enrolled Set (ES) of subjects enrolled prior to the approval of Protocol Amendment 2 1200 mg infusions delivered every other week (Q2W) for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles Enrolled Set (ES) of subjects enrolled prior to the approval of Protocol Amendment 2 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles
Overall Participants 244 498 508 1250
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
0
0%
Between 18 and 65 years
239
98%
489
98.2%
490
96.5%
1218
97.4%
>=65 years
5
2%
9
1.8%
18
3.5%
32
2.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
41.0
(12.0)
41.9
(11.5)
42.5
(11.9)
42.0
(11.7)
Sex: Female, Male (Count of Participants)
Female
226
92.6%
467
93.8%
478
94.1%
1171
93.7%
Male
18
7.4%
31
6.2%
30
5.9%
79
6.3%

Outcome Measures

1. Primary Outcome
Title Number of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks)
Description A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
Time Frame During the treatment period (through Week 96)

Outcome Measure Data

Analysis Population Description
Safety Set (SS) which consisted of all subjects who had received at least 1 partial dose of study medication during SL0012. A partial dose of study medication was defined as any infusion during which the subject received more than (>) 0mL of study medication.
Arm/Group Title Enrollment Cohort 1 Epratuzumab 600 mg Per Week (ES) Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (ES) Enrollment Cohort 2 Epratuzumab 600 mg Per Week (ES) All Epratuzumab 600 mg Per Week All Subjects
Arm/Group Description Enrolled Set (ES) of subjects enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Enrolled Set (ES) of subjects enrolled prior to the approval of Protocol Amendment 2 1200 mg infusions delivered every other week (Q2W) for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles Enrolled Set (ES) of subjects enrolled prior to the approval of Protocol Amendment 2 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Subjects receiving 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles and subjects receiving 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles
Measure Participants 244 497 507 751 1248
Count of Participants [Participants]
26
10.7%
45
9%
25
4.9%
51
4.1%
96
NaN
2. Primary Outcome
Title Percentage of Subjects Prematurely Discontinuing Due to a Treatment-emergent Adverse Event (TEAE) During the Treatment Period (Maximum 96 Weeks)
Description A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
Time Frame During the treatment period (through Week 96)

Outcome Measure Data

Analysis Population Description
Safety Set (SS) which consisted of all subjects who had received at least 1 partial dose of study medication during SL0012. A partial dose of study medication was defined as any infusion during which the subject received >0mL of study medication.
Arm/Group Title Enrollment Cohort 1 Epratuzumab 600 mg Per Week Enrollment Cohort 2 Epratuzumab 1200 mg Q2W Enrollment Cohort 2 Epratuzumab 600 mg Per Week All Epratuzumab 600 mg Per Week All Subjects
Arm/Group Description Subjects enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Subjects enrolled after approval of Protocol Amendment 2. 1200 mg infusions delivered every other week (Q2W) for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles Subjects enrolled after approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Subjects receiving 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles and subjects receiving 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles
Measure Participants 244 497 507 751 1248
Number [percentage of participants]
10.7
4.4%
9.1
1.8%
4.9
1%
6.8
0.5%
7.7
NaN
3. Primary Outcome
Title Number of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks)
Description A SAE is a treatment-emergent adverse event (TEAE) that the investigator classifies as serious. This includes: Death Life-threatening Significant or persistent disability/incapacity Congenital anomaly/birth defect (including that occurring in a fetus) Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or subject and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious Initial inpatient hospitalization or prolongation of hospitalization
Time Frame During the treatment period (through Week 96)

Outcome Measure Data

Analysis Population Description
Safety Set (SS) which consisted of all subjects who had received at least 1 partial dose of study medication during SL0012. A partial dose of study medication was defined as any infusion during which the subject received >0mL of study medication.
Arm/Group Title Enrollment Cohort 1 Epratuzumab 600 mg Per Week Enrollment Cohort 2 Epratuzumab 1200 mg Q2W Enrollment Cohort 2 Epratuzumab 600 mg Per Week All Epratuzumab 600 mg Per Week All Subjects
Arm/Group Description Subjects enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Subjects enrolled after approval of Protocol Amendment 2. 1200 mg infusions delivered every other week (Q2W) for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles Subjects enrolled after approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Subjects receiving 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles and subjects receiving 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles
Measure Participants 244 497 507 751 1248
Count of Participants [Participants]
81
33.2%
119
23.9%
104
20.5%
185
14.8%
304
NaN
4. Primary Outcome
Title Percentage of Subjects Reporting at Least 1 Serious Adverse Event (SAE) During the Treatment Period (Maximum 96 Weeks)
Description A SAE is a treatment-emergent adverse event (TEAE) that the investigator classifies as serious. This includes: Death Life-threatening Significant or persistent disability/incapacity Congenital anomaly/birth defect (including that occurring in a fetus) Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or subject and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious Initial inpatient hospitalization or prolongation of hospitalization
Time Frame During the treatment period (through Week 96)

Outcome Measure Data

Analysis Population Description
Safety Set (SS) which consisted of all subjects who had received at least 1 partial dose of study medication during SL0012. A partial dose of study medication was defined as any infusion during which the subject received >0mL of study medication.
Arm/Group Title Enrollment Cohort 1 Epratuzumab 600 mg Per Week Enrollment Cohort 2 Epratuzumab 1200 mg Q2W Enrollment Cohort 2 Epratuzumab 600 mg Per Week All Epratuzumab 600 mg Per Week All Subjects
Arm/Group Description Subjects enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Subjects enrolled after approval of Protocol Amendment 2. 1200 mg infusions delivered every other week (Q2W) for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles Subjects enrolled after approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Subjects receiving 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles and subjects receiving 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles
Measure Participants 244 497 507 751 1248
Number [percentage of participants]
33.2
13.6%
23.9
4.8%
20.5
4%
24.6
2%
24.4
NaN
5. Secondary Outcome
Title Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index
Description Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials.
Time Frame At Week 48

Outcome Measure Data

Analysis Population Description
The Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365) or SL0010 (NCT01261793) prior to enrollment in SL0012.
Arm/Group Title Enrollment Cohort 1 Epratuzumab 600 mg Per Week (FASS1) Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (FASS1) Enrollment Cohort 2 Epratuzumab 600 mg Per Week (FASS1) All Epratuzumab 600 mg Per Week (FASS1) All Subjects (FASS1)
Arm/Group Description Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 1200 mg infusions delivered every other week (Q2W) for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. Subjects receiving 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles and subjects receiving 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles
Measure Participants 230 488 494 724 1212
Count of Participants [Participants]
82
33.6%
146
29.3%
134
26.4%
216
17.3%
362
NaN
6. Secondary Outcome
Title Percentage of Subjects Meeting Treatment Response Criteria According to a Combined Response Index
Description Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials.
Time Frame Week 48

Outcome Measure Data

Analysis Population Description
The Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365) or SL0010 (NCT01261793) prior to enrollment in SL0012.
Arm/Group Title Enrollment Cohort 1 Epratuzumab 600 mg Per Week (FASS1) Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (FASS1) Enrollment Cohort 2 Epratuzumab 600 mg Per Week (FASS1) All Epratuzumab 600 mg Per Week (FASS1) All Subjects (FASS1)
Arm/Group Description Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 1200 mg infusions delivered every other week (Q2W) for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. Subjects receiving 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles and subjects receiving 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles
Measure Participants 230 488 494 724 1212
Number [percentage of participants]
35.7
14.6%
29.9
6%
27.1
5.3%
29.8
2.4%
29.9
NaN
7. Secondary Outcome
Title Number of Subjects Meeting Treatment Response Criteria According to a Combined Response Index
Description Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials.
Time Frame Week 96

Outcome Measure Data

Analysis Population Description
The Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365) or SL0010 (NCT01261793) prior to enrollment in SL0012, and with available results at the Week 96 time-point.
Arm/Group Title Enrollment Cohort 1 Epratuzumab 600 mg Per Week (FASS1) Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (FASS1) Enrollment Cohort 2 Epratuzumab 600 mg Per Week (FASS1) All Epratuzumab 600 mg Per Week (FASS1) All Subjects (FASS1)
Arm/Group Description Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 1200 mg infusions delivered every other week (Q2W) for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. Subjects receiving 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles and subjects receiving 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles
Measure Participants 186 306 298 484 790
Count of Participants [Participants]
74
30.3%
66
13.3%
78
15.4%
152
12.2%
218
NaN
8. Secondary Outcome
Title The Percent of Subjects Meeting Treatment Response Criteria According to a Combined Response Index
Description Combined response index is a response variable (yes/no) incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): (1) British Isles Lupus Activity Group (BILAG) improvement, (2) No worsening in Systemic Lupus Erythematosus Activity Index (SLEDAI), (3) No worsening in Physician's Global Assessment of Disease, and (4) No disallowed changes in concomitant medications, with disallowed changes including mainly increases in corticosteroids, immunosuppressants, and antimalarials.
Time Frame Week 96

Outcome Measure Data

Analysis Population Description
The Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365) or SL0010 (NCT01261793) prior to enrollment in SL0012, and with available results at the Week 96 time-point.
Arm/Group Title Enrollment Cohort 1 Epratuzumab 600 mg Per Week (FASS1) Enrollment Cohort 2 Epratuzumab 1200 mg Q2W (FASS1) Enrollment Cohort 2 Epratuzumab 600 mg Per Week (FASS1) All Epratuzumab 600 mg Per Week (FASS1) All Subjects (FASS1)
Arm/Group Description Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 1200 mg infusions delivered every other week (Q2W) for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Full Analysis Subset 1 (FASS1) consisted of all subjects in the FAS who were enrolled in study SL0008 (NCT00660881), SL0009 (NCT01262365), or SL0010 (NCT01261793) prior to enrollment in SL0012. Subjects were enrolled prior to the approval of Protocol Amendment 2. Subjects receiving 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles and subjects receiving 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles
Measure Participants 186 306 298 484 790
Number [percentage of participants]
39.8
16.3%
21.6
4.3%
26.2
5.2%
31.4
2.5%
27.6
NaN

Adverse Events

Time Frame Adverse events were collected from Visit 1 until Safety Follow-Up Visit (up to Week 196)
Adverse Event Reporting Description
Arm/Group Title Enrollment Cohort 1 Epratuzumab 600 mg Per Week Enrollment Cohort 2 Epratuzumab 1200 mg Q2W Enrollment Cohort 2 Epratuzumab 600 mg Per Week All Epratuzumab 600 mg Per Week All Subjects
Arm/Group Description Subjects enrolled prior to the approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Subjects enrolled after approval of Protocol Amendment 2. 1200 mg infusions delivered every other week (Q2W) for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles Subjects enrolled after approval of Protocol Amendment 2. 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles Subjects receiving 600 mg infusions delivered weekly for a total of 4 consecutive weeks (cumulative dose 2400 mg) over sixteen 12-week treatment cycles and subjects receiving 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over sixteen 12 week treatment cycles
All Cause Mortality
Enrollment Cohort 1 Epratuzumab 600 mg Per Week Enrollment Cohort 2 Epratuzumab 1200 mg Q2W Enrollment Cohort 2 Epratuzumab 600 mg Per Week All Epratuzumab 600 mg Per Week All Subjects
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 4/244 (1.6%) 4/497 (0.8%) 1/507 (0.2%) 5/751 (0.7%) 9/1248 (0.7%)
Serious Adverse Events
Enrollment Cohort 1 Epratuzumab 600 mg Per Week Enrollment Cohort 2 Epratuzumab 1200 mg Q2W Enrollment Cohort 2 Epratuzumab 600 mg Per Week All Epratuzumab 600 mg Per Week All Subjects
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 81/244 (33.2%) 119/497 (23.9%) 104/507 (20.5%) 185/751 (24.6%) 304/1248 (24.4%)
Blood and lymphatic system disorders
Anaemia 1/244 (0.4%) 1 2/497 (0.4%) 2 1/507 (0.2%) 2 2/751 (0.3%) 3 4/1248 (0.3%) 5
Leukopenia 0/244 (0%) 0 1/497 (0.2%) 1 2/507 (0.4%) 2 2/751 (0.3%) 2 3/1248 (0.2%) 3
Neutropenia 0/244 (0%) 0 2/497 (0.4%) 2 1/507 (0.2%) 1 1/751 (0.1%) 1 3/1248 (0.2%) 3
Thrombocytopenia 0/244 (0%) 0 1/497 (0.2%) 1 2/507 (0.4%) 2 2/751 (0.3%) 2 3/1248 (0.2%) 3
Eosinophilia 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Haemorrhagic diathesis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Lymphadenopathy 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Pancytopenia 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Splenic cyst 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Cardiac disorders
Myocardial infarction 2/244 (0.8%) 2 1/497 (0.2%) 1 0/507 (0%) 0 2/751 (0.3%) 2 3/1248 (0.2%) 3
Pericarditis 0/244 (0%) 0 1/497 (0.2%) 1 1/507 (0.2%) 1 1/751 (0.1%) 1 2/1248 (0.2%) 2
Acute myocardial infarction 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Angina pectoris 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Atrioventricular block complete 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Bradycardia 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Cardiac failure congestive 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Pleuropericarditis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Sinoatrial block 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Supraventricular tachycardia 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 2 1/751 (0.1%) 2 1/1248 (0.1%) 2
Tachycardia 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Cardiac arrest 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Congenital, familial and genetic disorders
Factor VII deficiency 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Ear and labyrinth disorders
Vertigo 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Endocrine disorders
Adrenal insufficiency 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Toxic nodular goitre 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Eye disorders
Cataract 1/244 (0.4%) 1 0/497 (0%) 0 1/507 (0.2%) 1 2/751 (0.3%) 2 2/1248 (0.2%) 2
Amaurosis fugax 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Necrotising retinitis 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Panophthalmitis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Retinal disorder 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Gastrointestinal disorders
Vomiting 1/244 (0.4%) 2 3/497 (0.6%) 3 3/507 (0.6%) 3 4/751 (0.5%) 5 7/1248 (0.6%) 8
Diarrhoea 0/244 (0%) 0 3/497 (0.6%) 3 3/507 (0.6%) 3 3/751 (0.4%) 3 6/1248 (0.5%) 6
Abdominal pain 1/244 (0.4%) 1 3/497 (0.6%) 3 1/507 (0.2%) 1 2/751 (0.3%) 2 5/1248 (0.4%) 5
Nausea 2/244 (0.8%) 3 1/497 (0.2%) 1 1/507 (0.2%) 1 3/751 (0.4%) 4 4/1248 (0.3%) 5
Pancreatitis 0/244 (0%) 0 3/497 (0.6%) 3 1/507 (0.2%) 1 1/751 (0.1%) 1 4/1248 (0.3%) 4
Gastritis 1/244 (0.4%) 1 1/497 (0.2%) 1 1/507 (0.2%) 1 2/751 (0.3%) 2 3/1248 (0.2%) 3
Abdominal pain upper 1/244 (0.4%) 1 1/497 (0.2%) 1 0/507 (0%) 0 1/751 (0.1%) 1 2/1248 (0.2%) 2
Dysphagia 1/244 (0.4%) 1 1/497 (0.2%) 1 0/507 (0%) 0 1/751 (0.1%) 1 2/1248 (0.2%) 2
Pancreatitis acute 0/244 (0%) 0 1/497 (0.2%) 1 1/507 (0.2%) 3 1/751 (0.1%) 3 2/1248 (0.2%) 4
Anal fissure 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Colitis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Colitis ischaemic 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Constipation 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Crohn's disease 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Eosinophilic colitis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Gastritis haemorrhagic 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Gastrointestinal haemorrhage 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Gastrooesophageal reflux disease 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Hiatus hernia 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Impaired gastric emptying 0/244 (0%) 0 1/497 (0.2%) 2 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 2
Inflammatory bowel disease 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Intestinal obstruction 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Oedematous pancreatitis 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 2 1/751 (0.1%) 2 1/1248 (0.1%) 2
Oesophageal disorder 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Oesophageal motility disorder 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Oesophageal spasm 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Peptic ulcer 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Peritoneal haemorrhage 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Salivary gland calculus 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Subileus 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
General disorders
Chest pain 1/244 (0.4%) 1 4/497 (0.8%) 4 8/507 (1.6%) 9 9/751 (1.2%) 10 13/1248 (1%) 14
Non-cardiac chest pain 2/244 (0.8%) 2 2/497 (0.4%) 2 0/507 (0%) 0 2/751 (0.3%) 2 4/1248 (0.3%) 4
Pyrexia 1/244 (0.4%) 1 2/497 (0.4%) 2 1/507 (0.2%) 1 2/751 (0.3%) 2 4/1248 (0.3%) 4
Asthenia 1/244 (0.4%) 1 1/497 (0.2%) 1 0/507 (0%) 0 1/751 (0.1%) 1 2/1248 (0.2%) 2
Drug interaction 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Drug intolerance 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Hyperthermia 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Impaired healing 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Local swelling 1/244 (0.4%) 2 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 2 1/1248 (0.1%) 2
Oedema peripheral 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Serositis 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Hepatobiliary disorders
Cholelithiasis 2/244 (0.8%) 2 2/497 (0.4%) 2 0/507 (0%) 0 2/751 (0.3%) 2 4/1248 (0.3%) 4
Cholecystitis 0/244 (0%) 0 0/497 (0%) 0 3/507 (0.6%) 3 3/751 (0.4%) 3 3/1248 (0.2%) 3
Bile duct stone 0/244 (0%) 0 0/497 (0%) 0 2/507 (0.4%) 3 2/751 (0.3%) 3 2/1248 (0.2%) 3
Cholangitis 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Cholecystitis acute 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Cholelithiasis migration 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Hepatic steatosis 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Immune system disorders
Drug hypersensitivity 0/244 (0%) 0 1/497 (0.2%) 1 1/507 (0.2%) 1 1/751 (0.1%) 1 2/1248 (0.2%) 2
Anaphylactic reaction 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Infections and infestations
Pneumonia 6/244 (2.5%) 6 7/497 (1.4%) 7 9/507 (1.8%) 10 15/751 (2%) 16 22/1248 (1.8%) 23
Sepsis 3/244 (1.2%) 4 3/497 (0.6%) 3 4/507 (0.8%) 4 7/751 (0.9%) 8 10/1248 (0.8%) 11
Cellulitis 1/244 (0.4%) 1 4/497 (0.8%) 4 3/507 (0.6%) 5 4/751 (0.5%) 6 8/1248 (0.6%) 10
Gastroenteritis 2/244 (0.8%) 2 3/497 (0.6%) 3 2/507 (0.4%) 2 4/751 (0.5%) 4 7/1248 (0.6%) 7
Arthritis bacterial 1/244 (0.4%) 1 2/497 (0.4%) 3 0/507 (0%) 0 1/751 (0.1%) 1 3/1248 (0.2%) 4
Diverticulitis 1/244 (0.4%) 1 1/497 (0.2%) 1 1/507 (0.2%) 1 2/751 (0.3%) 2 3/1248 (0.2%) 3
Gastroenteritis salmonella 1/244 (0.4%) 1 1/497 (0.2%) 1 1/507 (0.2%) 1 2/751 (0.3%) 2 3/1248 (0.2%) 3
Influenza 2/244 (0.8%) 2 0/497 (0%) 0 1/507 (0.2%) 1 3/751 (0.4%) 3 3/1248 (0.2%) 3
Pyelonephritis 1/244 (0.4%) 1 0/497 (0%) 0 2/507 (0.4%) 2 3/751 (0.4%) 3 3/1248 (0.2%) 3
Urinary tract infection 0/244 (0%) 0 1/497 (0.2%) 1 2/507 (0.4%) 3 2/751 (0.3%) 3 3/1248 (0.2%) 4
Bronchitis 1/244 (0.4%) 1 1/497 (0.2%) 1 0/507 (0%) 0 1/751 (0.1%) 1 2/1248 (0.2%) 2
Clostridium difficile colitis 0/244 (0%) 0 2/497 (0.4%) 2 0/507 (0%) 0 0/751 (0%) 0 2/1248 (0.2%) 2
Clostridium difficile infection 1/244 (0.4%) 1 1/497 (0.2%) 1 0/507 (0%) 0 1/751 (0.1%) 1 2/1248 (0.2%) 2
Meningitis viral 1/244 (0.4%) 1 1/497 (0.2%) 1 0/507 (0%) 0 1/751 (0.1%) 1 2/1248 (0.2%) 2
Subcutaneous abscess 0/244 (0%) 0 2/497 (0.4%) 2 0/507 (0%) 0 0/751 (0%) 0 2/1248 (0.2%) 2
Upper respiratory tract infection 0/244 (0%) 0 0/497 (0%) 0 2/507 (0.4%) 2 2/751 (0.3%) 2 2/1248 (0.2%) 2
Abscess 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Abscess limb 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Anal abscess 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Appendicitis 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Bronchopneumonia 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Cystitis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Cytomegalovirus chorioretinitis 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Cytomegalovirus infection 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Endocarditis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Epstein-Barr virus infection 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Escherichia bacteraemia 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Escherichia sepsis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Gangrene 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
H1N1 influenza 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Haematoma infection 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Hepatitis B 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Herpes zoster 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Lobar pneumonia 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Lower respiratory tract infection 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Meningitis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Meningitis aseptic 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Meningitis bacterial 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Pelvic inflammatory disease 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Perineal abscess 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Pneumonia bacterial 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Pneumonia legionella 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Pneumonia streptococcal 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Pyelonephritis acute 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Respiratory tract infection 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Salpingitis 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Tooth abscess 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Injury, poisoning and procedural complications
Meniscus injury 3/244 (1.2%) 3 0/497 (0%) 0 0/507 (0%) 0 3/751 (0.4%) 3 3/1248 (0.2%) 3
Tendon rupture 0/244 (0%) 0 1/497 (0.2%) 1 2/507 (0.4%) 3 2/751 (0.3%) 3 3/1248 (0.2%) 4
Ankle fracture 0/244 (0%) 0 1/497 (0.2%) 1 1/507 (0.2%) 1 1/751 (0.1%) 1 2/1248 (0.2%) 2
Fibula fracture 0/244 (0%) 0 1/497 (0.2%) 1 1/507 (0.2%) 1 1/751 (0.1%) 1 2/1248 (0.2%) 2
Head injury 0/244 (0%) 0 1/497 (0.2%) 1 1/507 (0.2%) 1 1/751 (0.1%) 1 2/1248 (0.2%) 2
Joint dislocation 0/244 (0%) 0 1/497 (0.2%) 1 1/507 (0.2%) 1 1/751 (0.1%) 1 2/1248 (0.2%) 2
Laceration 1/244 (0.4%) 1 1/497 (0.2%) 1 0/507 (0%) 0 1/751 (0.1%) 1 2/1248 (0.2%) 2
Radius fracture 2/244 (0.8%) 2 0/497 (0%) 0 0/507 (0%) 0 2/751 (0.3%) 2 2/1248 (0.2%) 2
Road traffic accident 0/244 (0%) 0 1/497 (0.2%) 1 1/507 (0.2%) 1 1/751 (0.1%) 1 2/1248 (0.2%) 2
Sternal fracture 0/244 (0%) 0 1/497 (0.2%) 1 1/507 (0.2%) 1 1/751 (0.1%) 1 2/1248 (0.2%) 2
Wrist fracture 0/244 (0%) 0 1/497 (0.2%) 1 1/507 (0.2%) 1 1/751 (0.1%) 1 2/1248 (0.2%) 2
Accidental overdose 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Concussion 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Contusion 0/244 (0%) 0 1/497 (0.2%) 2 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 2
Delayed recovery from anaesthesia 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Femoral neck fracture 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Femur fracture 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Hip fracture 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Ligament rupture 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Lumbar vertebral fracture 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Nail avulsion 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Overdose 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Post procedural complication 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Rib fracture 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Spinal column injury 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Spinal fracture 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Tendon injury 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Tibia fracture 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Upper limb fracture 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Investigations
Biopsy liver 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Blood cortisol decreased 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Electrocardiogram QT prolonged 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Transaminases increased 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Troponin increased 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Metabolism and nutrition disorders
Dehydration 0/244 (0%) 0 1/497 (0.2%) 1 2/507 (0.4%) 2 2/751 (0.3%) 2 3/1248 (0.2%) 3
Diabetes mellitus inadequate control 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Hypoglycaemia 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Hypokalaemia 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Hyponatraemia 0/244 (0%) 0 1/497 (0.2%) 2 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 2
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus 7/244 (2.9%) 7 13/497 (2.6%) 15 12/507 (2.4%) 12 19/751 (2.5%) 19 32/1248 (2.6%) 34
Osteoarthritis 1/244 (0.4%) 1 2/497 (0.4%) 4 2/507 (0.4%) 2 3/751 (0.4%) 3 5/1248 (0.4%) 7
Arthralgia 1/244 (0.4%) 1 2/497 (0.4%) 2 1/507 (0.2%) 1 2/751 (0.3%) 2 4/1248 (0.3%) 4
Arthritis 0/244 (0%) 0 1/497 (0.2%) 1 3/507 (0.6%) 3 3/751 (0.4%) 3 4/1248 (0.3%) 4
Osteonecrosis 2/244 (0.8%) 2 0/497 (0%) 0 1/507 (0.2%) 1 3/751 (0.4%) 3 3/1248 (0.2%) 3
Back pain 1/244 (0.4%) 1 0/497 (0%) 0 1/507 (0.2%) 1 2/751 (0.3%) 2 2/1248 (0.2%) 2
Bursitis 0/244 (0%) 0 0/497 (0%) 0 2/507 (0.4%) 2 2/751 (0.3%) 2 2/1248 (0.2%) 2
Foot deformity 0/244 (0%) 0 1/497 (0.2%) 1 1/507 (0.2%) 1 1/751 (0.1%) 1 2/1248 (0.2%) 2
Intervertebral disc disorder 0/244 (0%) 0 2/497 (0.4%) 2 0/507 (0%) 0 0/751 (0%) 0 2/1248 (0.2%) 2
Intervertebral disc protrusion 1/244 (0.4%) 1 0/497 (0%) 0 1/507 (0.2%) 1 2/751 (0.3%) 2 2/1248 (0.2%) 2
Chondromalacia 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Enthesopathy 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Fasciitis 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Muscular weakness 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Myalgia 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Osteoporotic fracture 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Pain in extremity 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Patellofemoral pain syndrome 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Periarthritis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Rotator cuff syndrome 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
SLE arthritis 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Soft tissue necrosis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Spinal osteoarthritis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Spondylolisthesis 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Synovial cyst 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Tenosynovitis stenosans 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin 1/244 (0.4%) 1 0/497 (0%) 0 2/507 (0.4%) 2 3/751 (0.4%) 3 3/1248 (0.2%) 3
Uterine leiomyoma 0/244 (0%) 0 2/497 (0.4%) 2 0/507 (0%) 0 0/751 (0%) 0 2/1248 (0.2%) 2
Adenocarcinoma of colon 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Adenocarcinoma pancreas 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Bladder cancer 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Bowen's disease 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Breast cancer stage I 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Cervix carcinoma stage 0 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Gastric cancer 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Myeloproliferative disorder 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Neuroendocrine carcinoma of the skin 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Ovarian adenoma 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Squamous cell carcinoma 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Nervous system disorders
Headache 0/244 (0%) 0 2/497 (0.4%) 2 4/507 (0.8%) 5 4/751 (0.5%) 5 6/1248 (0.5%) 7
Transient ischaemic attack 3/244 (1.2%) 3 0/497 (0%) 0 3/507 (0.6%) 3 6/751 (0.8%) 6 6/1248 (0.5%) 6
Cerebrovascular accident 1/244 (0.4%) 1 0/497 (0%) 0 3/507 (0.6%) 3 4/751 (0.5%) 4 4/1248 (0.3%) 4
Migraine 0/244 (0%) 0 2/497 (0.4%) 2 2/507 (0.4%) 2 2/751 (0.3%) 2 4/1248 (0.3%) 4
Syncope 0/244 (0%) 0 3/497 (0.6%) 3 1/507 (0.2%) 1 1/751 (0.1%) 1 4/1248 (0.3%) 4
Convulsion 0/244 (0%) 0 2/497 (0.4%) 2 1/507 (0.2%) 2 1/751 (0.1%) 2 3/1248 (0.2%) 4
Dizziness 0/244 (0%) 0 2/497 (0.4%) 2 1/507 (0.2%) 1 1/751 (0.1%) 1 3/1248 (0.2%) 3
Hypoaesthesia 0/244 (0%) 0 3/497 (0.6%) 3 0/507 (0%) 0 0/751 (0%) 0 3/1248 (0.2%) 3
Dysarthria 0/244 (0%) 0 2/497 (0.4%) 2 0/507 (0%) 0 0/751 (0%) 0 2/1248 (0.2%) 2
Grand mal convulsion 1/244 (0.4%) 1 0/497 (0%) 0 1/507 (0.2%) 1 2/751 (0.3%) 2 2/1248 (0.2%) 2
Monoparesis 0/244 (0%) 0 1/497 (0.2%) 1 1/507 (0.2%) 2 1/751 (0.1%) 2 2/1248 (0.2%) 3
Altered state of consciousness 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Cerebral haemorrhage 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Cerebral infarction 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Cerebrospinal fluid leakage 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Cerebrovascular disorder 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Epilepsy 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Haemorrhage intracranial 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Hemiparesis 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Ischaemic stroke 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Lumbar radiculopathy 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Lupus encephalitis 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Memory impairment 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Motor dysfunction 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Myasthenia gravis 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Neuropsychiatric lupus 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Optic neuritis 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Polyneuropathy 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Radiculitis brachial 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Radiculopathy 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Seizure anoxic 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Sinus headache 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Thecal sac compression 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Thoracic outlet syndrome 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Transverse sinus thrombosis 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
VIIth nerve paralysis 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous 3/244 (1.2%) 3 0/497 (0%) 0 1/507 (0.2%) 1 4/751 (0.5%) 4 4/1248 (0.3%) 4
Foetal death 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Premature delivery 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Psychiatric disorders
Depression 0/244 (0%) 0 2/497 (0.4%) 2 2/507 (0.4%) 2 2/751 (0.3%) 2 4/1248 (0.3%) 4
Suicide attempt 0/244 (0%) 0 2/497 (0.4%) 2 2/507 (0.4%) 2 2/751 (0.3%) 2 4/1248 (0.3%) 4
Psychotic disorder 0/244 (0%) 0 2/497 (0.4%) 2 0/507 (0%) 0 0/751 (0%) 0 2/1248 (0.2%) 2
Suicidal ideation 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Renal and urinary disorders
Lupus nephritis 2/244 (0.8%) 2 3/497 (0.6%) 3 1/507 (0.2%) 1 3/751 (0.4%) 3 6/1248 (0.5%) 6
Proteinuria 0/244 (0%) 0 2/497 (0.4%) 2 2/507 (0.4%) 2 2/751 (0.3%) 2 4/1248 (0.3%) 4
Renal failure acute 0/244 (0%) 0 1/497 (0.2%) 1 2/507 (0.4%) 3 2/751 (0.3%) 3 3/1248 (0.2%) 4
Nephrolithiasis 2/244 (0.8%) 2 0/497 (0%) 0 0/507 (0%) 0 2/751 (0.3%) 2 2/1248 (0.2%) 2
Glomerulonephritis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Glomerulonephritis membranoproliferative 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Kidney fibrosis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Nephritis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Renal colic 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Stress urinary incontinence 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Reproductive system and breast disorders
Ovarian cyst 1/244 (0.4%) 1 1/497 (0.2%) 1 2/507 (0.4%) 2 3/751 (0.4%) 3 4/1248 (0.3%) 4
Endometriosis 2/244 (0.8%) 2 1/497 (0.2%) 1 0/507 (0%) 0 2/751 (0.3%) 2 3/1248 (0.2%) 3
Cervical dysplasia 2/244 (0.8%) 2 0/497 (0%) 0 0/507 (0%) 0 2/751 (0.3%) 2 2/1248 (0.2%) 2
Menorrhagia 1/244 (0.4%) 1 0/497 (0%) 0 1/507 (0.2%) 1 2/751 (0.3%) 2 2/1248 (0.2%) 2
Uterine polyp 1/244 (0.4%) 1 0/497 (0%) 0 1/507 (0.2%) 1 2/751 (0.3%) 2 2/1248 (0.2%) 2
Adenomyosis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Endometrial hyperplasia 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Pelvic pain 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Uterine haemorrhage 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Vaginal prolapse 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Respiratory, thoracic and mediastinal disorders
Dyspnoea 1/244 (0.4%) 1 3/497 (0.6%) 3 1/507 (0.2%) 1 2/751 (0.3%) 2 5/1248 (0.4%) 5
Pulmonary embolism 2/244 (0.8%) 2 0/497 (0%) 0 1/507 (0.2%) 1 3/751 (0.4%) 3 3/1248 (0.2%) 3
Cough 0/244 (0%) 0 0/497 (0%) 0 2/507 (0.4%) 2 2/751 (0.3%) 2 2/1248 (0.2%) 2
Pleurisy 0/244 (0%) 0 2/497 (0.4%) 2 0/507 (0%) 0 0/751 (0%) 0 2/1248 (0.2%) 2
Acute pulmonary oedema 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Acute respiratory failure 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Asthma 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Chronic obstructive pulmonary disease 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Chronic respiratory failure 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Dyspnoea exertional 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Emphysema 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Laryngeal stenosis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Pleural effusion 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Pulmonary arterial hypertension 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Pulmonary hypertension 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Respiratory failure 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Wheezing 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Skin and subcutaneous tissue disorders
Skin ulcer 1/244 (0.4%) 1 1/497 (0.2%) 1 1/507 (0.2%) 1 2/751 (0.3%) 2 3/1248 (0.2%) 3
Cutaneous vasculitis 1/244 (0.4%) 1 1/497 (0.2%) 1 0/507 (0%) 0 1/751 (0.1%) 1 2/1248 (0.2%) 2
Blister 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Chronic cutaneous lupus erythematosus 0/244 (0%) 0 1/497 (0.2%) 2 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 2
Pruritus generalised 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Systemic lupus erythematosus rash 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Urticaria 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Surgical and medical procedures
Abortion induced 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Cholecystectomy 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Hip arthroplasty 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Joint arthroplasty 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Polymedication 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Shoulder operation 1/244 (0.4%) 1 0/497 (0%) 0 0/507 (0%) 0 1/751 (0.1%) 1 1/1248 (0.1%) 1
Vascular disorders
Deep vein thrombosis 3/244 (1.2%) 3 0/497 (0%) 0 2/507 (0.4%) 2 5/751 (0.7%) 5 5/1248 (0.4%) 5
Hypertension 0/244 (0%) 0 3/497 (0.6%) 3 0/507 (0%) 0 0/751 (0%) 0 3/1248 (0.2%) 3
Venous thrombosis 0/244 (0%) 0 2/497 (0.4%) 2 0/507 (0%) 0 0/751 (0%) 0 2/1248 (0.2%) 2
Arterial occlusive disease 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Hypertensive crisis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Orthostatic hypotension 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Temporal arteritis 0/244 (0%) 0 1/497 (0.2%) 1 0/507 (0%) 0 0/751 (0%) 0 1/1248 (0.1%) 1
Venous thrombosis limb 0/244 (0%) 0 0/497 (0%) 0 1/507 (0.2%) 1 1/751 (0.1%) 1 1/1248 (0.1%) 1
Other (Not Including Serious) Adverse Events
Enrollment Cohort 1 Epratuzumab 600 mg Per Week Enrollment Cohort 2 Epratuzumab 1200 mg Q2W Enrollment Cohort 2 Epratuzumab 600 mg Per Week All Epratuzumab 600 mg Per Week All Subjects
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 177/244 (72.5%) 296/497 (59.6%) 306/507 (60.4%) 483/751 (64.3%) 779/1248 (62.4%)
Gastrointestinal disorders
Nausea 39/244 (16%) 80 59/497 (11.9%) 86 62/507 (12.2%) 79 101/751 (13.4%) 159 160/1248 (12.8%) 245
Diarrhoea 27/244 (11.1%) 41 47/497 (9.5%) 58 34/507 (6.7%) 47 61/751 (8.1%) 88 108/1248 (8.7%) 146
Vomiting 22/244 (9%) 45 32/497 (6.4%) 43 29/507 (5.7%) 38 51/751 (6.8%) 83 83/1248 (6.7%) 126
Fatigue 17/244 (7%) 24 19/497 (3.8%) 22 21/507 (4.1%) 22 38/751 (5.1%) 46 57/1248 (4.6%) 68
Infections and infestations
Upper respiratory tract infection 66/244 (27%) 140 76/497 (15.3%) 126 82/507 (16.2%) 120 148/751 (19.7%) 260 224/1248 (17.9%) 386
Urinary tract infection 56/244 (23%) 124 61/497 (12.3%) 88 62/507 (12.2%) 90 118/751 (15.7%) 214 179/1248 (14.3%) 302
Nasopharyngitis 38/244 (15.6%) 56 42/497 (8.5%) 65 45/507 (8.9%) 67 83/751 (11.1%) 123 125/1248 (10%) 188
Bronchitis 34/244 (13.9%) 38 35/497 (7%) 38 35/507 (6.9%) 41 69/751 (9.2%) 79 104/1248 (8.3%) 117
Sinusitis 25/244 (10.2%) 40 41/497 (8.2%) 48 38/507 (7.5%) 48 63/751 (8.4%) 88 104/1248 (8.3%) 136
Influenza 15/244 (6.1%) 16 22/497 (4.4%) 24 21/507 (4.1%) 23 36/751 (4.8%) 39 58/1248 (4.6%) 63
Gastroenteritis 14/244 (5.7%) 14 19/497 (3.8%) 21 17/507 (3.4%) 23 31/751 (4.1%) 37 50/1248 (4%) 58
Conjunctivitis 14/244 (5.7%) 16 15/497 (3%) 17 8/507 (1.6%) 8 22/751 (2.9%) 24 37/1248 (3%) 41
Musculoskeletal and connective tissue disorders
Back pain 34/244 (13.9%) 47 31/497 (6.2%) 32 32/507 (6.3%) 32 66/751 (8.8%) 79 97/1248 (7.8%) 111
Arthralgia 24/244 (9.8%) 40 36/497 (7.2%) 44 30/507 (5.9%) 38 54/751 (7.2%) 78 90/1248 (7.2%) 122
Systemic lupus erythematosus 15/244 (6.1%) 19 18/497 (3.6%) 26 23/507 (4.5%) 30 38/751 (5.1%) 49 56/1248 (4.5%) 75
Pain in extremity 15/244 (6.1%) 21 15/497 (3%) 17 19/507 (3.7%) 21 34/751 (4.5%) 42 49/1248 (3.9%) 59
Muscle spasms 13/244 (5.3%) 14 18/497 (3.6%) 20 6/507 (1.2%) 7 19/751 (2.5%) 21 37/1248 (3%) 41
Bursitis 15/244 (6.1%) 24 9/497 (1.8%) 11 7/507 (1.4%) 7 22/751 (2.9%) 31 31/1248 (2.5%) 42
Nervous system disorders
Headache 46/244 (18.9%) 66 67/497 (13.5%) 84 57/507 (11.2%) 80 103/751 (13.7%) 146 170/1248 (13.6%) 230
Dizziness 20/244 (8.2%) 26 23/497 (4.6%) 30 23/507 (4.5%) 25 43/751 (5.7%) 51 66/1248 (5.3%) 81
Hypoaesthesia 13/244 (5.3%) 15 9/497 (1.8%) 9 12/507 (2.4%) 13 25/751 (3.3%) 28 34/1248 (2.7%) 37
Psychiatric disorders
Depression 16/244 (6.6%) 17 23/497 (4.6%) 23 15/507 (3%) 16 31/751 (4.1%) 33 54/1248 (4.3%) 56
Respiratory, thoracic and mediastinal disorders
Cough 21/244 (8.6%) 25 30/497 (6%) 31 32/507 (6.3%) 43 53/751 (7.1%) 68 83/1248 (6.7%) 99
Oropharyngeal pain 15/244 (6.1%) 24 9/497 (1.8%) 11 14/507 (2.8%) 16 29/751 (3.9%) 40 38/1248 (3%) 51
Urticaria 13/244 (5.3%) 20 7/497 (1.4%) 7 4/507 (0.8%) 4 17/751 (2.3%) 24 24/1248 (1.9%) 31
Vascular disorders
Hypertension 17/244 (7%) 19 26/497 (5.2%) 28 26/507 (5.1%) 27 43/751 (5.7%) 46 69/1248 (5.5%) 74

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

Name/Title UCB
Organization Cares
Phone +1844 599 ext 2273
Email UCBCares@ucb.com
Responsible Party:
UCB Pharma
ClinicalTrials.gov Identifier:
NCT01408576
Other Study ID Numbers:
  • SL0012
  • 2010-020859-30
First Posted:
Aug 3, 2011
Last Update Posted:
Oct 3, 2018
Last Verified:
Mar 1, 2016