CANTOS: Cardiovascular Risk Reduction Study (Reduction in Recurrent Major CV Disease Events)

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01327846

Collaborator

(none)

10,066

Enrollment

1133

Locations

Arms

96.1

Actual Duration (Months)

8.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Main Study (CACZ885M2301): The purpose of the pivotal phase of this trial was to test the hypothesis that canakinumab treatment of patients with myocardial infarction (MI) at least one month prior to study entry and elevated hsCRP could prevent recurrent cardiovascular events.

The purpose of the extension phase of the main study is to collect additional long-term safety data on continued exposure to canakinumab in patients who participated in the pivotal phase.

Sub-study 1 (CACZ885M2301S1): The purpose of this sub-study was to evaluate the effect of quarterly subcutaneous canakinumab treatment for 24 months comparted with placebo on the carotid plaque burden measured by integrated vascular MRI in patients enrolled in the CACZ885M2301 study (CANTOS).

Sub-study 2 (CACZ885M2301S2): The purpose of this CANTOS sub-study was to determine whether, in patients with type 2 diabetes participating in the CANTOS main study, canakinumab compared to placebo, on top of standard of care could increase insulin secretion and insulin sensitivity.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis	Drug: Canakinumab Drug: Placebo Drug: Standard of care	Phase 3

Detailed Description

Sub-study 1 and 2 were terminated prior to data collection from subjects. However, there is an ongoing extension trial where patients are receiving open-drug label.

Study Design

Study Type:

Interventional

Actual Enrollment :

10066 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled, Event-driven Trial of Quarterly Subcutaneous Canakinumab in the Prevention of Recurrent Cardiovascular Events Among Stable Post-myocardial Infarction Patients With Elevated hsCRP

Actual Study Start Date :

Apr 11, 2011

Actual Primary Completion Date :

Mar 28, 2017

Actual Study Completion Date :

Apr 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Canakinumab Dose 50 mg Pivotal Phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care therapy. Extension Phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care therapy	Drug: Canakinumab Other Names: ACZ885 Drug: Standard of care Standard of care post-MI background therapy includes, but is not limited to, lipid lowering, anti-hypertensive, beta blockers, and anti-platelet therapy as appropriate
Experimental: Canakinumab Dose 150 mg Pivotal Phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care therapy	Drug: Canakinumab Other Names: ACZ885 Drug: Standard of care Standard of care post-MI background therapy includes, but is not limited to, lipid lowering, anti-hypertensive, beta blockers, and anti-platelet therapy as appropriate
Experimental: Canakinumab Dose 300 mg Pivotal Phase: Blinded Canakinumab 300 mg quarterly subcutaneous (with one additional dose at week 2) + standard of care therapy. Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care therapy	Drug: Canakinumab Other Names: ACZ885 Drug: Standard of care Standard of care post-MI background therapy includes, but is not limited to, lipid lowering, anti-hypertensive, beta blockers, and anti-platelet therapy as appropriate
Placebo Comparator: Placebo Pivotal Phase: Blinded matching placebo quarterly subcutaneous + standard of care therapy. Extension Phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care therapy	Drug: Placebo Drug: Standard of care Standard of care post-MI background therapy includes, but is not limited to, lipid lowering, anti-hypertensive, beta blockers, and anti-platelet therapy as appropriate

Outcome Measures

Primary Outcome Measures

Analysis of Core Phase First CEC Confirmed Major Adverse Cardiovascular Events (MACE) and Its Components [From randomization, to end of treatment plus 30 days, up to approximately 6 years]
Time to occurrence of CEC (Cardiovascular clinical events adjudication committee) confirmed MACE, which was a composite endpoint consisting of CEC confirmed CV death, CEC confirmed non-fatal MI,or CEC confirmed non-fatal stroke. Patients with the CEC adjudicated reason for death of "Unknown" were counted as CV (cardiovascular) death.
Substudy 1 (Core Phase): Change From Baseline in Carotid Plaque Burden in the Bifurcation Region of the Index Carotid Artery [24 months]
Substudy 2 (Core Phase): Change From Baseline of the Insulin Secretion Rate (ISR) Relative to Glucose 0-30 Min Defined as Φ30 = AUCISR 0-30 / AUCGluc 0-30 Averaged Across the Year 3, 4, 5 Visits [From randomization up to approximately 6 years]

Secondary Outcome Measures

Patients With Core Phase CEC Confirmed CV Death, Non-fatal MI, Non-fatal Stroke, or Hospitalization for Unstable Angina Requiring Unplanned Revascularization [From randomization, to end of treatment pus 30 days, up to approximately 6 years]
Occurrence of the composite cardiovascular endpoint consisting of cardiovascular death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina requiring unplanned revascularization. MACE includes CV death, non-fatal MI and non-fatal stroke. CEC = Clinical Endpoints Committee
Patients With Core Phase New Onset Type 2 Diabetes Among Patients With Pre-diabetes at Randomization [From randomization up to approximately 6 years]
Time to CEC confirmed new onset of type 2 diabetes among those with pre-diabetes at randomization (i.e. excluding those that are normoglycemic at baseline)
Core Phase All-cause Mortality, Non-fatal MI, or Non-fatal Stroke [From randomization, to end of treatment plus 30 days, up to approximately 6 years]
Occurrence of the composite endpoint consisting of all-cause mortality, non-fatal IM, or non-fatal stroke
Core Phase All-cause Mortality [From randomization, to end of treatment plus 30 days, up to approximately 6 years]
Number of participant deaths
Summary of Adverse Events (Core Phase) [From randomization, to end of treatment plus 30 days, up to approximately 6 years]
Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs) occurring during the double-blind Core phase of the study. AEs/SAEs are any signs or symptoms that occur during the study treatment.
Summary of Adverse Events (Extension Phase) [From start of Extension phase, to end of treatment plus 30 days, up to approximately 2 years]
Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs) occurring during the Extension phase of the study. AEs/SAEs are any signs or symptoms that occur during the study treatment.
Substudy 1 (Core Phase): Change From Baseline of the Total Vessel Wall Area at Month 3 in the Bifurcation Region of the Index Carotid Artery [3 months]
Substudy 1 (Core Phase): Mean Total Vessel Wall Area Across the Left and Right Carotid Artery at Month 3 and Month 24 [24 months]
Substudy 1 (Core Phase): Change From Baseline in Corresponding Total Vessel Wall Area in the Left and Right Carotid Arteries [24 months]
Substudy 1 (Core Phase): The Existence of a Baseline Total Vessel Wall Area by Treatment Interaction as Well as the Consistency of the Treatment Effect Across Subgroups [24 months]
Substudy 2 (Core Phase): Change From Baseline in Insulin Sensitivity Index [From randomization up to approximately 6 years]
Substudy 2 (Core Phase): Change From Baseline in OGTT Stimulated Area Under Curve (AUC) 0-120 Min of Glucose Concentration, Insulin Concentration, Pro-insulin Concentration, and Insulin Concentration/Glucose Concentration Ratio [From randomization up to approximately 6 years]
Substudy 2 (Core Phase): Change From Baseline in Fasting Pro-Insulin Concentration/Insulin Concentration Ratio [From randomization up to approximately 6 years]
Substudy 2 (Core Phase): Change From Baseline in OGTT Stimulated Area Under the Curve (AUC) 0-120 Min of C-peptide Concentration [From randomization up to approximately 6 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Main Study Inclusion Criteria:

Written informed consent
Male, or Female of non-child-bearing potential
Age ≥ 18 years.
Spontaneous MI at least 30 days before randomization. hsCRP ≥ 2 mg/L

Substudy 1 Inclusion:

All Inclusion from Main Study
Acquisition of evaluable baseline MRI images of bilateral carotid arteries by the imaging core laboratory

Substudy 2 Inclusion:

All inclusion from Main Study
T2D at baseline per Main protocol criteria and be on a stable anti-hyperglycemic medication for at least 4 weeks prior to the baseline OGTT test
Willing to have the OGTT assessment started before 10 am

Main Study Exclusion Criteria:

Pregnant or nursing (lactating) women
Women of child-bearing potential
Any of the following concomitant diseases
Planned coronary revascularization (PCI or CABG)
Major non-cardiac surgical or endoscopic procedure within past 6 months
Multi-vessel CABG surgery within the past 3 years
Symptomatic patients with Class IV heart failure (HF) (New York Heart Association [NYHA].
Uncontrolled hypertension
Uncontrolled diabetes
History or evidence of active tuberculosis (TB) infection Substudy 1 Exclusion
All Main exclusion
Patients with prior history of carotid angioplasty, stenting, or carotid atherectomy
Patients with contraindications to MRI examination (brain aneurysm clip, implanted neural stimulator, implanted cardiac pacemaker, pacemaker wires or defibrillator, prosthetic heart valves, cochlear implant, ocular foreign body or other implanted body, tattoos, implanted insulin pump, metal shrapnel or bullet)
Patients prone to claustrophobia or known anxiety disorders
BMI > 40 kg/m2 Substudy 2 Exclusion
This sub-study does not have any additional exclusion criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Athens	Alabama	United States	35611
2	Novartis Investigative Site	Birmingham	Alabama	United States	35235-3424
3	Novartis Investigative Site	Birmingham	Alabama	United States	35243
4	Novartis Investigative Site	Birmingham	Alabama	United States	35294-2041
5	Novartis Investigative Site	Fairhope	Alabama	United States	36532
6	Novartis Investigative Site	Huntsville	Alabama	United States	35801
7	Novartis Investigative Site	Mobile	Alabama	United States	36604
8	Novartis Investigative Site	Mobile	Alabama	United States	36608
9	Novartis Investigative Site	Mobile	Alabama	United States	36617-2293
10	Novartis Investigative Site	Anchorage	Alaska	United States	99508
11	Novartis Investigative Site	Chandler	Arizona	United States	85224
12	Novartis Investigative Site	Glendale	Arizona	United States	85306
13	Novartis Investigative Site	Phoenix	Arizona	United States	85018
14	Novartis Investigative Site	Phoenix	Arizona	United States	85032
15	Novartis Investigative Site	Hot Springs	Arkansas	United States	71913
16	Novartis Investigative Site	Jonesboro	Arkansas	United States	72401
17	Novartis Investigative Site	Little Rock	Arkansas	United States	72204
18	Novartis Investigative Site	Beverly Hills	California	United States	90211
19	Novartis Investigative Site	Carmichael	California	United States	95608
20	Novartis Investigative Site	Escondido	California	United States	92025
21	Novartis Investigative Site	Fullerton	California	United States	92835
22	Novartis Investigative Site	Huntington Beach	California	United States	92647
23	Novartis Investigative Site	Lancaster	California	United States	93534
24	Novartis Investigative Site	Loma Linda	California	United States	92354
25	Novartis Investigative Site	Loma Linda	California	United States	92357
26	Novartis Investigative Site	Long Beach	California	United States	90806
27	Novartis Investigative Site	Los Angeles	California	United States	90033
28	Novartis Investigative Site	Los Angeles	California	United States	90073
29	Novartis Investigative Site	Los Gatos	California	United States	95032
30	Novartis Investigative Site	Mission Viejo	California	United States	92691
31	Novartis Investigative Site	Newport Beach	California	United States	92663
32	Novartis Investigative Site	Northridge	California	United States	91325
33	Novartis Investigative Site	Oceanside	California	United States	92056
34	Novartis Investigative Site	Orangevale	California	United States	95662
35	Novartis Investigative Site	Palm Springs	California	United States	92262
36	Novartis Investigative Site	Pasadena	California	United States	91105
37	Novartis Investigative Site	Pomona	California	United States	91767
38	Novartis Investigative Site	Sacramento	California	United States	95816
39	Novartis Investigative Site	Sacramento	California	United States	95819
40	Novartis Investigative Site	San Diego	California	United States	92101
41	Novartis Investigative Site	San Diego	California	United States	92120
42	Novartis Investigative Site	San Diego	California	United States	92128
43	Novartis Investigative Site	San Diego	California	United States	92161
44	Novartis Investigative Site	San Francisco	California	United States	94143-0792
45	Novartis Investigative Site	Santa Ana	California	United States	92704
46	Novartis Investigative Site	Santa Rosa	California	United States	95405
47	Novartis Investigative Site	Torrance	California	United States	90502
48	Novartis Investigative Site	Tustin	California	United States	92780
49	Novartis Investigative Site	Visalia	California	United States	93291
50	Novartis Investigative Site	Walnut Creek	California	United States	94598
51	Novartis Investigative Site	Aurora	Colorado	United States	80012
52	Novartis Investigative Site	Colorado Springs	Colorado	United States	80907
53	Novartis Investigative Site	Denver	Colorado	United States	80204-4507
54	Novartis Investigative Site	Denver	Colorado	United States	80206
55	Novartis Investigative Site	Denver	Colorado	United States	80218
56	Novartis Investigative Site	Denver	Colorado	United States	80220
57	Novartis Investigative Site	Norwich	Connecticut	United States	06360
58	Novartis Investigative Site	Newark	Delaware	United States	19713
59	Novartis Investigative Site	Washington	District of Columbia	United States	20010
60	Novartis Investigative Site	Washington	District of Columbia	United States	20037
61	Novartis Investigative Site	Clearwater	Florida	United States	33756
62	Novartis Investigative Site	Coral Springs	Florida	United States	33065
63	Novartis Investigative Site	Davie	Florida	United States	33324
64	Novartis Investigative Site	Daytona Beach	Florida	United States	32114
65	Novartis Investigative Site	DeFuniak Springs	Florida	United States	32435
66	Novartis Investigative Site	Doral	Florida	United States	33136
67	Novartis Investigative Site	Hialeah	Florida	United States	33012
68	Novartis Investigative Site	Hollywood	Florida	United States	33021
69	Novartis Investigative Site	Hollywood	Florida	United States	33312
70	Novartis Investigative Site	Jacksonville Beach	Florida	United States	32050
71	Novartis Investigative Site	Jacksonville	Florida	United States	32204
72	Novartis Investigative Site	Jacksonville	Florida	United States	32209-6511
73	Novartis Investigative Site	Jacksonville	Florida	United States	32216
74	Novartis Investigative Site	Jacksonville	Florida	United States	32223
75	Novartis Investigative Site	Jupiter	Florida	United States	33458
76	Novartis Investigative Site	Miami Beach	Florida	United States	33140
77	Novartis Investigative Site	Miami	Florida	United States	33126
78	Novartis Investigative Site	Miami	Florida	United States	33135
79	Novartis Investigative Site	Miami	Florida	United States	33155
80	Novartis Investigative Site	Miami	Florida	United States	33176
81	Novartis Investigative Site	Naples	Florida	United States	34119
82	Novartis Investigative Site	Orlando	Florida	United States	32822
83	Novartis Investigative Site	Pembroke Pines	Florida	United States	33024
84	Novartis Investigative Site	Pinellas Park	Florida	United States	33781
85	Novartis Investigative Site	Port Charlotte	Florida	United States	33952
86	Novartis Investigative Site	Port Orange	Florida	United States	32127
87	Novartis Investigative Site	Sarasota	Florida	United States	34239
88	Novartis Investigative Site	South Miami	Florida	United States	33143
89	Novartis Investigative Site	Tampa	Florida	United States	33613
90	Novartis Investigative Site	Tampa	Florida	United States	33624
91	Novartis Investigative Site	Wellington	Florida	United States	33449
92	Novartis Investigative Site	Athens	Georgia	United States	30606
93	Novartis Investigative Site	Augusta	Georgia	United States	30904
94	Novartis Investigative Site	Covington	Georgia	United States	30014
95	Novartis Investigative Site	Cumming	Georgia	United States	30041
96	Novartis Investigative Site	Decatur	Georgia	United States	30033
97	Novartis Investigative Site	Decatur	Georgia	United States	30035
98	Novartis Investigative Site	Duluth	Georgia	United States	30096
99	Novartis Investigative Site	Macon	Georgia	United States	31201
100	Novartis Investigative Site	Roswell	Georgia	United States	30076
101	Novartis Investigative Site	Savannah	Georgia	United States	31406
102	Novartis Investigative Site	Thomasville	Georgia	United States	31792
103	Novartis Investigative Site	Honolulu	Hawaii	United States	96814
104	Novartis Investigative Site	Coeur d'Alene	Idaho	United States	83814
105	Novartis Investigative Site	Chicago	Illinois	United States	60611
106	Novartis Investigative Site	Jerseyville	Illinois	United States	62052
107	Novartis Investigative Site	Lombard	Illinois	United States	60148
108	Novartis Investigative Site	Melrose Park	Illinois	United States	60160
109	Novartis Investigative Site	Peoria	Illinois	United States	61602
110	Novartis Investigative Site	Evansville	Indiana	United States	47712
111	Novartis Investigative Site	Evansville	Indiana	United States	47714
112	Novartis Investigative Site	Ames	Iowa	United States	50010
113	Novartis Investigative Site	Waterloo	Iowa	United States	50702
114	Novartis Investigative Site	Kansas City	Kansas	United States	66160
115	Novartis Investigative Site	Overland Park	Kansas	United States	66204
116	Novartis Investigative Site	Topeka	Kansas	United States	66606
117	Novartis Investigative Site	Wichita	Kansas	United States	67207
118	Novartis Investigative Site	Wichita	Kansas	United States	67214
119	Novartis Investigative Site	Lexington	Kentucky	United States	40509
120	Novartis Investigative Site	Louisville	Kentucky	United States	40206
121	Novartis Investigative Site	Madisonville	Kentucky	United States	42431
122	Novartis Investigative Site	Owensboro	Kentucky	United States	42303
123	Novartis Investigative Site	Baton Rouge	Louisiana	United States	70808
124	Novartis Investigative Site	Baton Rouge	Louisiana	United States	70816
125	Novartis Investigative Site	Covington	Louisiana	United States	70433
126	Novartis Investigative Site	Houma	Louisiana	United States	70360
127	Novartis Investigative Site	Lafayette	Louisiana	United States	70501
128	Novartis Investigative Site	Lafayette	Louisiana	United States	70508
129	Novartis Investigative Site	Mandeville	Louisiana	United States	70471
130	Novartis Investigative Site	Metairie	Louisiana	United States	70001
131	Novartis Investigative Site	Metairie	Louisiana	United States	70006
132	Novartis Investigative Site	Minden	Louisiana	United States	71055
133	Novartis Investigative Site	New Orleans	Louisiana	United States	70115
134	Novartis Investigative Site	New Orleans	Louisiana	United States	70119
135	Novartis Investigative Site	Opelousas	Louisiana	United States	70570
136	Novartis Investigative Site	Shreveport	Louisiana	United States	71101
137	Novartis Investigative Site	Shreveport	Louisiana	United States	71103
138	Novartis Investigative Site	Slidell	Louisiana	United States	70458
139	Novartis Investigative Site	Winnsboro	Louisiana	United States	71295
140	Novartis Investigative Site	Zachary	Louisiana	United States	70791
141	Novartis Investigative Site	Portland	Maine	United States	04102
142	Novartis Investigative Site	Baltimore	Maryland	United States	21204
143	Novartis Investigative Site	Beltsville	Maryland	United States	20705
144	Novartis Investigative Site	Columbia	Maryland	United States	21044
145	Novartis Investigative Site	Burlington	Massachusetts	United States	01803
146	Novartis Investigative Site	Fall River	Massachusetts	United States	02720
147	Novartis Investigative Site	Haverhill	Massachusetts	United States	01830
148	Novartis Investigative Site	Ann Arbor	Michigan	United States	48106
149	Novartis Investigative Site	Chelsea	Michigan	United States	48118
150	Novartis Investigative Site	Detroit	Michigan	United States	48202
151	Novartis Investigative Site	Grand Blanc	Michigan	United States	48439
152	Novartis Investigative Site	Kalamazoo	Michigan	United States	49008
153	Novartis Investigative Site	Midland	Michigan	United States	48640
154	Novartis Investigative Site	Novi	Michigan	United States	48374
155	Novartis Investigative Site	Petoskey	Michigan	United States	49770
156	Novartis Investigative Site	Royal Oak	Michigan	United States	48073
157	Novartis Investigative Site	Saginaw	Michigan	United States	48601
158	Novartis Investigative Site	Wyoming	Michigan	United States	49519
159	Novartis Investigative Site	Bloomington	Minnesota	United States	55420
160	Novartis Investigative Site	Duluth	Minnesota	United States	55805
161	Novartis Investigative Site	Edina	Minnesota	United States	55435
162	Novartis Investigative Site	Fridley	Minnesota	United States	55432
163	Novartis Investigative Site	Minneapolis	Minnesota	United States	55433
164	Novartis Investigative Site	Robbinsdale	Minnesota	United States	55422
165	Novartis Investigative Site	Saint Cloud	Minnesota	United States	56303
166	Novartis Investigative Site	Saint Paul	Minnesota	United States	55102
167	Novartis Investigative Site	Hattiesburg	Mississippi	United States	39401
168	Novartis Investigative Site	Jackson	Mississippi	United States	39209
169	Novartis Investigative Site	Picayune	Mississippi	United States	39466
170	Novartis Investigative Site	Columbia	Missouri	United States	65212
171	Novartis Investigative Site	Kansas City	Missouri	United States	64111
172	Novartis Investigative Site	Saint Louis	Missouri	United States	63110
173	Novartis Investigative Site	Saint Louis	Missouri	United States	63128
174	Novartis Investigative Site	Saint Louis	Missouri	United States	63141
175	Novartis Investigative Site	Springfield	Missouri	United States	65807
176	Novartis Investigative Site	Grand Island	Nebraska	United States	68803
177	Novartis Investigative Site	Lincoln	Nebraska	United States	68516
178	Novartis Investigative Site	Omaha	Nebraska	United States	68114
179	Novartis Investigative Site	Omaha	Nebraska	United States	68131
180	Novartis Investigative Site	Omaha	Nebraska	United States	68134
181	Novartis Investigative Site	Las Vegas	Nevada	United States	89118
182	Novartis Investigative Site	Nashua	New Hampshire	United States	03060
183	Novartis Investigative Site	Camden	New Jersey	United States	08103
184	Novartis Investigative Site	Freehold	New Jersey	United States	07728
185	Novartis Investigative Site	Lodi	New Jersey	United States	07644
186	Novartis Investigative Site	New Brunswick	New Jersey	United States	08901
187	Novartis Investigative Site	Ocean City	New Jersey	United States	07712
188	Novartis Investigative Site	Pomona	New Jersey	United States	08240
189	Novartis Investigative Site	Ridgewood	New Jersey	United States	07450
190	Novartis Investigative Site	Westwood	New Jersey	United States	07675
191	Novartis Investigative Site	Albuquerque	New Mexico	United States	87102
192	Novartis Investigative Site	Binghamton	New York	United States	13901
193	Novartis Investigative Site	Endwell	New York	United States	13760
194	Novartis Investigative Site	Kew Gardens	New York	United States	11415
195	Novartis Investigative Site	Mineola	New York	United States	11501
196	Novartis Investigative Site	New York	New York	United States	10003
197	Novartis Investigative Site	New York	New York	United States	10016
198	Novartis Investigative Site	New York	New York	United States	10035
199	Novartis Investigative Site	Rochester	New York	United States	14609
200	Novartis Investigative Site	Rochester	New York	United States	14621
201	Novartis Investigative Site	Asheboro	North Carolina	United States	27204
202	Novartis Investigative Site	Charlotte	North Carolina	United States	28277
203	Novartis Investigative Site	Greensboro	North Carolina	United States	27401
204	Novartis Investigative Site	Greensboro	North Carolina	United States	27410
205	Novartis Investigative Site	Greenville	North Carolina	United States	27834
206	Novartis Investigative Site	Hickory	North Carolina	United States	28601
207	Novartis Investigative Site	Mooresville	North Carolina	United States	28117
208	Novartis Investigative Site	Pinehurst	North Carolina	United States	28374
209	Novartis Investigative Site	Salisbury	North Carolina	United States	28144
210	Novartis Investigative Site	Sanford	North Carolina	United States	27330
211	Novartis Investigative Site	Statesville	North Carolina	United States	28625
212	Novartis Investigative Site	Winston-Salem	North Carolina	United States	27103
213	Novartis Investigative Site	Winston-Salem	North Carolina	United States	27106
214	Novartis Investigative Site	Fargo	North Dakota	United States	58122
215	Novartis Investigative Site	Grand Forks	North Dakota	United States	58201
216	Novartis Investigative Site	Akron	Ohio	United States	44309
217	Novartis Investigative Site	Cincinnati	Ohio	United States	45219
218	Novartis Investigative Site	Cincinnati	Ohio	United States	45245
219	Novartis Investigative Site	Cleveland	Ohio	United States	44109-1998
220	Novartis Investigative Site	Columbus	Ohio	United States	43235
221	Novartis Investigative Site	Dayton	Ohio	United States	45402
222	Novartis Investigative Site	Marion	Ohio	United States	43302
223	Novartis Investigative Site	Bartlesville	Oklahoma	United States	74006
224	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73120
225	Novartis Investigative Site	Tulsa	Oklahoma	United States	74133
226	Novartis Investigative Site	Bend	Oregon	United States	97701
227	Novartis Investigative Site	Portland	Oregon	United States	97225
228	Novartis Investigative Site	Abington	Pennsylvania	United States	19001
229	Novartis Investigative Site	Altoona	Pennsylvania	United States	16602
230	Novartis Investigative Site	Beaver	Pennsylvania	United States	15009
231	Novartis Investigative Site	Bridgeville	Pennsylvania	United States	15017
232	Novartis Investigative Site	Camp Hill	Pennsylvania	United States	17011
233	Novartis Investigative Site	Erie	Pennsylvania	United States	16507
234	Novartis Investigative Site	Hershey	Pennsylvania	United States	17033
235	Novartis Investigative Site	Pittsburgh	Pennsylvania	United States	15216
236	Novartis Investigative Site	Pittsburgh	Pennsylvania	United States	15236
237	Novartis Investigative Site	Pittsburgh	Pennsylvania	United States	15243
238	Novartis Investigative Site	Pottstown	Pennsylvania	United States	19464
239	Novartis Investigative Site	Uniontown	Pennsylvania	United States	15401
240	Novartis Investigative Site	Cumberland	Rhode Island	United States	02864-1410
241	Novartis Investigative Site	Providence	Rhode Island	United States	02904
242	Novartis Investigative Site	Providence	Rhode Island	United States	02906
243	Novartis Investigative Site	Anderson	South Carolina	United States	29621
244	Novartis Investigative Site	Columbia	South Carolina	United States	29201
245	Novartis Investigative Site	Fort Mill	South Carolina	United States	29707
246	Novartis Investigative Site	Greenville	South Carolina	United States	29605
247	Novartis Investigative Site	Greer	South Carolina	United States	29651
248	Novartis Investigative Site	Moncks Corner	South Carolina	United States	29461
249	Novartis Investigative Site	Mount Pleasant	South Carolina	United States	29464
250	Novartis Investigative Site	North Myrtle Beach	South Carolina	United States	29582
251	Novartis Investigative Site	Orangeburg	South Carolina	United States	29115
252	Novartis Investigative Site	Varnville	South Carolina	United States	29944
253	Novartis Investigative Site	Rapid City	South Dakota	United States	57701
254	Novartis Investigative Site	Sioux Falls	South Dakota	United States	57104
255	Novartis Investigative Site	Germantown	Tennessee	United States	38138
256	Novartis Investigative Site	Greenville	Tennessee	United States	37745
257	Novartis Investigative Site	Jackson	Tennessee	United States	38305
258	Novartis Investigative Site	Johnson City	Tennessee	United States	37604
259	Novartis Investigative Site	Knoxville	Tennessee	United States	37917
260	Novartis Investigative Site	Knoxville	Tennessee	United States	37920
261	Novartis Investigative Site	Knoxville	Tennessee	United States	37934
262	Novartis Investigative Site	Memphis	Tennessee	United States	38120
263	Novartis Investigative Site	Allen	Texas	United States	75002-3688
264	Novartis Investigative Site	Beaumont	Texas	United States	77701
265	Novartis Investigative Site	Beaumont	Texas	United States	77702
266	Novartis Investigative Site	Bedford	Texas	United States	76021
267	Novartis Investigative Site	Brownsville	Texas	United States	78520
268	Novartis Investigative Site	Dallas	Texas	United States	75204
269	Novartis Investigative Site	Dallas	Texas	United States	75226
270	Novartis Investigative Site	Dallas	Texas	United States	75231
271	Novartis Investigative Site	Gonzales	Texas	United States	78629
272	Novartis Investigative Site	Greenville	Texas	United States	75401
273	Novartis Investigative Site	Houston	Texas	United States	77025
274	Novartis Investigative Site	Houston	Texas	United States	77030
275	Novartis Investigative Site	Houston	Texas	United States	77055
276	Novartis Investigative Site	Houston	Texas	United States	77064
277	Novartis Investigative Site	Houston	Texas	United States	77070
278	Novartis Investigative Site	Houston	Texas	United States	77081
279	Novartis Investigative Site	Irving	Texas	United States	75039
280	Novartis Investigative Site	Lake Jackson	Texas	United States	77566
281	Novartis Investigative Site	Leander	Texas	United States	78641
282	Novartis Investigative Site	Livingston	Texas	United States	77351
283	Novartis Investigative Site	Lufkin	Texas	United States	75904
284	Novartis Investigative Site	Marshall	Texas	United States	75670
285	Novartis Investigative Site	McAllen	Texas	United States	78501
286	Novartis Investigative Site	McKinney	Texas	United States	75069
287	Novartis Investigative Site	Odessa	Texas	United States	79761
288	Novartis Investigative Site	San Antonio	Texas	United States	78212
289	Novartis Investigative Site	San Antonio	Texas	United States	78229-3900
290	Novartis Investigative Site	San Antonio	Texas	United States	78229-4801
291	Novartis Investigative Site	San Antonio	Texas	United States	78229
292	Novartis Investigative Site	San Antonio	Texas	United States	78234
293	Novartis Investigative Site	San Antonio	Texas	United States	78238-7676
294	Novartis Investigative Site	San Antonio	Texas	United States	78258
295	Novartis Investigative Site	Sugar Land	Texas	United States	77479
296	Novartis Investigative Site	Temple	Texas	United States	76508
297	Novartis Investigative Site	Tomball	Texas	United States	77375
298	Novartis Investigative Site	Waco	Texas	United States	76710
299	Novartis Investigative Site	Webster	Texas	United States	77598
300	Novartis Investigative Site	Bountiful	Utah	United States	84010
301	Novartis Investigative Site	Layton	Utah	United States	84041
302	Novartis Investigative Site	Salt Lake City	Utah	United States	84102
303	Novartis Investigative Site	Salt Lake City	Utah	United States	84107
304	Novartis Investigative Site	Salt Lake City	Utah	United States	84124
305	Novartis Investigative Site	Burke	Virginia	United States	22015
306	Novartis Investigative Site	Danville	Virginia	United States	24541
307	Novartis Investigative Site	Hopewell	Virginia	United States	23860
308	Novartis Investigative Site	Richmond	Virginia	United States	23249
309	Novartis Investigative Site	Richmond	Virginia	United States	23298
310	Novartis Investigative Site	Port Orchard	Washington	United States	98366
311	Novartis Investigative Site	Renton	Washington	United States	98057
312	Novartis Investigative Site	Seattle	Washington	United States	98104
313	Novartis Investigative Site	Seattle	Washington	United States	98122
314	Novartis Investigative Site	Tacoma	Washington	United States	98405
315	Novartis Investigative Site	Madison	Wisconsin	United States	53713
316	Novartis Investigative Site	Bahía Blanca	Buenos Aires	Argentina	B8000AAT
317	Novartis Investigative Site	Caba	Buenos Aires	Argentina	1428
318	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1056ABJ
319	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1221ADC
320	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1425AGC
321	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1425BWO
322	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1440AAD
323	Novartis Investigative Site	Mar del Plata	Buenos Aires	Argentina	7600
324	Novartis Investigative Site	Mar del Plata	Buenos Aires	Argentina	B7600
325	Novartis Investigative Site	Quilmes	Buenos Aires	Argentina	B1878DVB
326	Novartis Investigative Site	Quilmes	Buenos Aires	Argentina	B1878GEG
327	Novartis Investigative Site	Ramos Mejia	Buenos Aires	Argentina	B1704ETD
328	Novartis Investigative Site	San Isidro	Buenos Aires	Argentina	B1642DCD
329	Novartis Investigative Site	San Nicolas	Buenos Aires	Argentina	B2900DMH
330	Novartis Investigative Site	Zarate	Buenos Aires	Argentina	2800
331	Novartis Investigative Site	Caba	Capital Federal	Argentina	C1179AAB
332	Novartis Investigative Site	Caba	Capital Federal	Argentina	C1430CKE
333	Novartis Investigative Site	San Salvador de Jujuy	Jujuy	Argentina	Y4600ABF
334	Novartis Investigative Site	Posadas	Misiones	Argentina	N3300AHX
335	Novartis Investigative Site	Cipolletti	Rio Negro	Argentina	8324
336	Novartis Investigative Site	Tucuman	San Miguel De Tucuman	Argentina	T4000ICL
337	Novartis Investigative Site	Rosario	Santa Fe	Argentina	S2000CXP
338	Novartis Investigative Site	Rosario	Santa Fe	Argentina	S2000DSV
339	Novartis Investigative Site	Rosario	Santa Fe	Argentina	S2000
340	Novartis Investigative Site	San Miguel de Tucuman	Tucuman	Argentina	T4000EBR
341	Novartis Investigative Site	San Miguel de Tucuman	Tucuman	Argentina	T4000IFL
342	Novartis Investigative Site	San Miguel de Tucuman	Tucuman	Argentina	T4000IIH
343	Novartis Investigative Site	Caba		Argentina	C1119ACN
344	Novartis Investigative Site	Cordoba		Argentina	5000
345	Novartis Investigative Site	Cordoba		Argentina	X5000AAJ
346	Novartis Investigative Site	Cordoba		Argentina	X5000AAW
347	Novartis Investigative Site	Cordoba		Argentina	X5000AAX
348	Novartis Investigative Site	Cordoba		Argentina	X5000EPU
349	Novartis Investigative Site	Cordoba		Argentina	X5000JJS
350	Novartis Investigative Site	Cordoba		Argentina	X5003DCE
351	Novartis Investigative Site	Cordoba		Argentina	X5003DCP
352	Novartis Investigative Site	Cordoba		Argentina	X5006CBI
353	Novartis Investigative Site	Cordoba		Argentina	X5009BSN
354	Novartis Investigative Site	Cordoba		Argentina	X5022CPU
355	Novartis Investigative Site	Cordoba		Argentina	X5220XAO
356	Novartis Investigative Site	Corrientes		Argentina	W3400CBI
357	Novartis Investigative Site	Corrientes		Argentina	W3400CLH
358	Novartis Investigative Site	Corrientes		Argentina	W3400
359	Novartis Investigative Site	Corrientes		Argentina	W3410AVV
360	Novartis Investigative Site	Formosa		Argentina	P3600
361	Novartis Investigative Site	Formosa		Argentina	P3634XAR
362	Novartis Investigative Site	Salta		Argentina	4400
363	Novartis Investigative Site	San Luis		Argentina	D5702JRS
364	Novartis Investigative Site	Santa Fe		Argentina	S3000EOZ
365	Novartis Investigative Site	Santa Fe		Argentina	S3000EPV
366	Novartis Investigative Site	Santa Fe		Argentina	S3000FWO
367	Novartis Investigative Site	Santiago del Estero		Argentina	G4200AQK
368	Novartis Investigative Site	Tucuman		Argentina	T4000HXU
369	Novartis Investigative Site	Garran	Australian Capital Territory	Australia	2606
370	Novartis Investigative Site	Gosford	New South Wales	Australia	2250
371	Novartis Investigative Site	Kogarah	New South Wales	Australia	2217
372	Novartis Investigative Site	Liverpool	New South Wales	Australia	2170
373	Novartis Investigative Site	Milton	Queensland	Australia	4064
374	Novartis Investigative Site	Southport	Queensland	Australia	4215
375	Novartis Investigative Site	Hobart	Tasmania	Australia	7000
376	Novartis Investigative Site	Bundoora	Victoria	Australia	3083
377	Novartis Investigative Site	Geelong	Victoria	Australia	3220
378	Novartis Investigative Site	Bateman	Western Australia	Australia	6150
379	Novartis Investigative Site	Joondalup	Western Australia	Australia	6027
380	Novartis Investigative Site	Perth	Western Australia	Australia	6000
381	Novartis Investigative Site	Graz		Austria	A-8036
382	Novartis Investigative Site	Linz		Austria	4010
383	Novartis Investigative Site	Linz		Austria	A-4010
384	Novartis Investigative Site	Saint Stefan		Austria	8511
385	Novartis Investigative Site	Salzburg		Austria	A-5020
386	Novartis Investigative Site	Vienna		Austria	1030
387	Novartis Investigative Site	Wien		Austria	A 1090
388	Novartis Investigative Site	Aalst		Belgium	9300
389	Novartis Investigative Site	Bonheiden		Belgium	2820
390	Novartis Investigative Site	Brasschaat		Belgium	2930
391	Novartis Investigative Site	Brussel		Belgium	1000
392	Novartis Investigative Site	De Pinte		Belgium	9840
393	Novartis Investigative Site	Genk		Belgium	3600
394	Novartis Investigative Site	Gent		Belgium	9000
395	Novartis Investigative Site	Hasselt		Belgium	3500
396	Novartis Investigative Site	Huy		Belgium	4500
397	Novartis Investigative Site	Leuven		Belgium	3000
398	Novartis Investigative Site	Mechelen		Belgium	2800
399	Novartis Investigative Site	Ottignies		Belgium	1340
400	Novartis Investigative Site	Tienen		Belgium	3300
401	Novartis Investigative Site	Salvador	BA	Brazil	40050-410
402	Novartis Investigative Site	Salvador	BA	Brazil	40140-110
403	Novartis Investigative Site	Fortaleza	CE	Brazil	60430 370
404	Novartis Investigative Site	Brasilia	DF	Brazil	70390-903
405	Novartis Investigative Site	Brasilia	DF	Brazil	70658-700
406	Novartis Investigative Site	Goiania	GO	Brazil	74223-130
407	Novartis Investigative Site	Goiania	GO	Brazil	74605-020
408	Novartis Investigative Site	Belo Horizonte	MG	Brazil	30130-060
409	Novartis Investigative Site	Belo Horizonte	MG	Brazil	30150-221
410	Novartis Investigative Site	Uberlandia	MG	Brazil	38405-320
411	Novartis Investigative Site	Uberlandia	Minas Gerais	Brazil	38411 186
412	Novartis Investigative Site	Campo Grande	MS	Brazil	79080-190
413	Novartis Investigative Site	Belem	PA	Brazil	66087-660
414	Novartis Investigative Site	Recife	PE	Brazil	52051-380
415	Novartis Investigative Site	Curitiba	PR	Brazil	80730-150
416	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
417	Novartis Investigative Site	Passo Fundo	RS	Brazil	99010-080
418	Novartis Investigative Site	Pelotas	RS	Brazil	96015-290
419	Novartis Investigative Site	Porto Alegre	RS	Brazil	90560-030
420	Novartis Investigative Site	Porto Alegre	RS	Brazil	90620 001
421	Novartis Investigative Site	Porto Alegre	RS	Brazil	90880-480
422	Novartis Investigative Site	Porto Alegre	RS	Brazil	91350 200
423	Novartis Investigative Site	Blumenau	SC	Brazil	89020 430
424	Novartis Investigative Site	Campinas	SP	Brazil	13010-001
425	Novartis Investigative Site	Campinas	SP	Brazil	13020-431
426	Novartis Investigative Site	Campinas	SP	Brazil	13060 080
427	Novartis Investigative Site	Santo Andre	SP	Brazil	09190-615
428	Novartis Investigative Site	Sao Jose do Rio Preto	SP	Brazil	15090 000
429	Novartis Investigative Site	Sao Paulo	SP	Brazil	01323 000
430	Novartis Investigative Site	Sao Paulo	SP	Brazil	04023-900
431	Novartis Investigative Site	Sao Paulo	SP	Brazil	05403-000
432	Novartis Investigative Site	São Paulo	SP	Brazil	05508-000
433	Novartis Investigative Site	Tatuí	SP	Brazil	18270-170
434	Novartis Investigative Site	Votuporanga	SP	Brazil	15500 003
435	Novartis Investigative Site	Pazardzhik		Bulgaria	4400
436	Novartis Investigative Site	Pleven		Bulgaria	5800
437	Novartis Investigative Site	Plovdiv		Bulgaria	4000
438	Novartis Investigative Site	Sofia		Bulgaria	1000
439	Novartis Investigative Site	Sofia		Bulgaria	1202
440	Novartis Investigative Site	Sofia		Bulgaria	1233
441	Novartis Investigative Site	Sofia		Bulgaria	1309
442	Novartis Investigative Site	Sofia		Bulgaria	1431
443	Novartis Investigative Site	Sofia		Bulgaria	1527
444	Novartis Investigative Site	Sofia		Bulgaria	1606
445	Novartis Investigative Site	New Westminster	British Columbia	Canada	V3L 3W4
446	Novartis Investigative Site	Surrey	British Columbia	Canada	V3V 0C6
447	Novartis Investigative Site	Victoria	British Columbia	Canada	V8R4R2
448	Novartis Investigative Site	Winnipeg	Manitoba	Canada	R2V 4W3
449	Novartis Investigative Site	Mount Pearl	Newfoundland and Labrador	Canada	A1N 1W7
450	Novartis Investigative Site	Halifax	Nova Scotia	Canada	B3H 3A7
451	Novartis Investigative Site	Cambridge	Ontario	Canada	N1R 6V6
452	Novartis Investigative Site	Etobicoke	Ontario	Canada	M9V 4B4
453	Novartis Investigative Site	Hamilton	Ontario	Canada	L8L 2X2
454	Novartis Investigative Site	Kitchener	Ontario	Canada	N2M 5N4
455	Novartis Investigative Site	Mississauga	Ontario	Canada	L5K 2L3
456	Novartis Investigative Site	Newmarket	Ontario	Canada	L3Y 2P7
457	Novartis Investigative Site	Newmarket	Ontario	Canada	L3Y 8C3
458	Novartis Investigative Site	Ottawa	Ontario	Canada	K1Y 4W7
459	Novartis Investigative Site	Peterborough	Ontario	Canada	K9J 0B2
460	Novartis Investigative Site	Scarborough	Ontario	Canada	M1P 2V5
461	Novartis Investigative Site	Toronto	Ontario	Canada	M5B 1N9
462	Novartis Investigative Site	Toronto	Ontario	Canada	M9W 4L6
463	Novartis Investigative Site	Drummondville	Quebec	Canada	J2B 7T1
464	Novartis Investigative Site	Gatineau	Quebec	Canada	J8Y 6S8
465	Novartis Investigative Site	Granby	Quebec	Canada	J2G 1T7
466	Novartis Investigative Site	Joliette	Quebec	Canada	J6E 6J2
467	Novartis Investigative Site	Lachine	Quebec	Canada	H8S 2E4
468	Novartis Investigative Site	Laval	Quebec	Canada	H7M 3L9
469	Novartis Investigative Site	Levis	Quebec	Canada	G6V 4Z5
470	Novartis Investigative Site	Longueuil	Quebec	Canada	J4M 2X1
471	Novartis Investigative Site	Montreal	Quebec	Canada	H3G 1A4
472	Novartis Investigative Site	Montreal	Quebec	Canada	H4J 1C5
473	Novartis Investigative Site	Sainte Foy	Quebec	Canada	G1V 4G5
474	Novartis Investigative Site	Sherbrooke	Quebec	Canada	J1G-2E8
475	Novartis Investigative Site	St-Jean-sur-Richelieu	Quebec	Canada	J3A 1J2
476	Novartis Investigative Site	Ste-Foy	Quebec	Canada	G1W 4R4
477	Novartis Investigative Site	Terrebonne	Quebec	Canada	J6V 2H2
478	Novartis Investigative Site	Thetford Mines	Quebec	Canada	G6G 2V4
479	Novartis Investigative Site	Saskatoon	Saskatchewan	Canada	S7H 5M3
480	Novartis Investigative Site	Quebec		Canada	G1G 3Y8
481	Novartis Investigative Site	Quebec		Canada	G1V 4G2
482	Novartis Investigative Site	Quebec		Canada	G3K 2P8
483	Novartis Investigative Site	Beijing	Beijing	China	100730
484	Novartis Investigative Site	Chongqing	Chongqing	China	400010
485	Novartis Investigative Site	Fuzhou	Fujian	China
486	Novartis Investigative Site	Guang Zhou	Guangdong	China	510000
487	Novartis Investigative Site	Guangzhou	Guangdong	China	51000
488	Novartis Investigative Site	Nanning	Guangxi	China	530021
489	Novartis Investigative Site	Shijiazhuang	Hebei	China	050000
490	Novartis Investigative Site	Harbin	Heilongjiang	China	150000
491	Novartis Investigative Site	Wuhan	Hubei	China	430022
492	Novartis Investigative Site	Wuhan	Hubei	China	430060
493	Novartis Investigative Site	Changsha	Hunan	China	410003
494	Novartis Investigative Site	Baotou	Inner Mongolia	China	014040
495	Novartis Investigative Site	Nanjing	Jiangsu	China	210009
496	Novartis Investigative Site	Suzhou	Jiangsu	China	215006
497	Novartis Investigative Site	Changchun	Jilin	China	130033
498	Novartis Investigative Site	Shenyang	Liaoning	China	110003
499	Novartis Investigative Site	Shenyang	Liaoning	China	110016
500	Novartis Investigative Site	Shanghai City	Shanghai	China	200120
501	Novartis Investigative Site	Shanghai	Shanghai	China	200032
502	Novartis Investigative Site	Shanghai	Shanghai	China
503	Novartis Investigative Site	Xian	Shanxi	China	710004
504	Novartis Investigative Site	Xian	Shanxi	China	710061
505	Novartis Investigative Site	Tianjin	Tianjin	China	300121
506	Novartis Investigative Site	Hangzhou	Zhejiang	China	310013
507	Novartis Investigative Site	Hangzhou	Zhejiang	China	310016
508	Novartis Investigative Site	Beijing		China	100010
509	Novartis Investigative Site	Beijing		China	100028
510	Novartis Investigative Site	Beijing		China	100029
511	Novartis Investigative Site	Beijing		China	100034
512	Novartis Investigative Site	Beijing		China	100038
513	Novartis Investigative Site	Beijing		China	100176
514	Novartis Investigative Site	Shanghai		China	200080
515	Novartis Investigative Site	Tianjin		China	300142
516	Novartis Investigative Site	Tianjin		China	30045
517	Novartis Investigative Site	Baranquilla	Atlantico	Colombia
518	Novartis Investigative Site	Barranquilla	Atlantico	Colombia
519	Novartis Investigative Site	Cartagena	Bolivar	Colombia
520	Novartis Investigative Site	Manizales	Caldas	Colombia	1700
521	Novartis Investigative Site	Bucaramanga	Santander	Colombia
522	Novartis Investigative Site	Floridablanca	Santander	Colombia	57-7
523	Novartis Investigative Site	Armenia		Colombia
524	Novartis Investigative Site	Baranquilla		Colombia
525	Novartis Investigative Site	Barranquilla		Colombia	080020
526	Novartis Investigative Site	Barranquilla		Colombia
527	Novartis Investigative Site	Bogota		Colombia
528	Novartis Investigative Site	Bogotá		Colombia
529	Novartis Investigative Site	Cali		Colombia
530	Novartis Investigative Site	Cartegena		Colombia
531	Novartis Investigative Site	Florida Blanca		Colombia
532	Novartis Investigative Site	Varazdin	HRV	Croatia	42000
533	Novartis Investigative Site	Cakovec		Croatia	40000
534	Novartis Investigative Site	Koprivnica		Croatia	48000
535	Novartis Investigative Site	Krapinske toplice		Croatia	49 217
536	Novartis Investigative Site	Krapinske Toplice		Croatia	49217
537	Novartis Investigative Site	Opatija		Croatia	51410
538	Novartis Investigative Site	Rijeka		Croatia	51000
539	Novartis Investigative Site	Virovitica		Croatia	33000
540	Novartis Investigative Site	Zagreb		Croatia	10000
541	Novartis Investigative Site	Brandys nad Labem	Czech Republic	Czechia	250 01
542	Novartis Investigative Site	Jablonec nad Nisou	Czech Republic	Czechia	466 01
543	Novartis Investigative Site	Kladno	Czech Republic	Czechia	272 80
544	Novartis Investigative Site	Liberec	Czech Republic	Czechia	460 05
545	Novartis Investigative Site	Louny	Czech Republic	Czechia
546	Novartis Investigative Site	Ostrava	Czech Republic	Czechia	70200
547	Novartis Investigative Site	Plzen	Czech Republic	Czechia	301 00
548	Novartis Investigative Site	Praha 11	Czech Republic	Czechia	148 00
549	Novartis Investigative Site	Praha 9	Czech Republic	Czechia
550	Novartis Investigative Site	Roznov pod Radhostem	Czech Republic	Czechia	756 61
551	Novartis Investigative Site	Semily	Czech Republic	Czechia	513 31
552	Novartis Investigative Site	Svitavy	Czech Republic	Czechia	568 25
553	Novartis Investigative Site	Trebic	Czech Republic	Czechia	674 01
554	Novartis Investigative Site	Usti nad Labem	Czech Republic	Czechia	400 01
555	Novartis Investigative Site	Usti nad Orlici	Czech Republic	Czechia	562 18
556	Novartis Investigative Site	Vyskov	Czech Republic	Czechia	68001
557	Novartis Investigative Site	Znojmo	Czech Republic	Czechia	66902
558	Novartis Investigative Site	Most	CZE	Czechia	434 01
559	Novartis Investigative Site	Praha 2	CZE	Czechia	128 08
560	Novartis Investigative Site	Trutnov	CZE	Czechia	46063
561	Novartis Investigative Site	Benesov		Czechia	25601
562	Novartis Investigative Site	Brno Bohunice		Czechia	625 00
563	Novartis Investigative Site	Broumov		Czechia	550 01
564	Novartis Investigative Site	Kolin		Czechia	280 20
565	Novartis Investigative Site	Marianske lazne		Czechia	353 01
566	Novartis Investigative Site	Pardubice		Czechia	530 02
567	Novartis Investigative Site	Prague 4 - Krc		Czechia	14059
568	Novartis Investigative Site	Praha		Czechia	12808
569	Novartis Investigative Site	Slany		Czechia	274 01
570	Novartis Investigative Site	Teplice		Czechia	415 29
571	Novartis Investigative Site	Uherske Hradiste		Czechia	68601
572	Novartis Investigative Site	Parnu		Estonia	80010
573	Novartis Investigative Site	Saku		Estonia	75501
574	Novartis Investigative Site	Tallinn		Estonia	10138
575	Novartis Investigative Site	Tallinn		Estonia	10611
576	Novartis Investigative Site	Tallinn		Estonia	13419
577	Novartis Investigative Site	Tallinn		Estonia	13619
578	Novartis Investigative Site	Tartu		Estonia	50410
579	Novartis Investigative Site	Viljandi County		Estonia	71024
580	Novartis Investigative Site	Võru		Estonia	65608
581	Novartis Investigative Site	Muehlheim An Der Ruhr	NRW	Germany	45468
582	Novartis Investigative Site	Bad Krozingen		Germany	79189
583	Novartis Investigative Site	Balve		Germany	58802
584	Novartis Investigative Site	Berlin		Germany	10117
585	Novartis Investigative Site	Berlin		Germany	10367
586	Novartis Investigative Site	Berlin		Germany	10629
587	Novartis Investigative Site	Berlin		Germany	10789
588	Novartis Investigative Site	Berlin		Germany	12627
589	Novartis Investigative Site	Berlin		Germany	13055
590	Novartis Investigative Site	Berlin		Germany	13353
591	Novartis Investigative Site	Bochum		Germany	44787
592	Novartis Investigative Site	Borna		Germany	04552
593	Novartis Investigative Site	Chemnitz		Germany	09122
594	Novartis Investigative Site	Chemnitz		Germany	09130
595	Novartis Investigative Site	Dillingen		Germany	66763
596	Novartis Investigative Site	Dinslaken		Germany	46535
597	Novartis Investigative Site	Dortmund		Germany	44137
598	Novartis Investigative Site	Dresden		Germany	01067
599	Novartis Investigative Site	Dresden		Germany	01069
600	Novartis Investigative Site	Dresden		Germany	01277
601	Novartis Investigative Site	Dresden		Germany	01307
602	Novartis Investigative Site	Dresden		Germany	01309
603	Novartis Investigative Site	Duisburg		Germany	47137
604	Novartis Investigative Site	Düsseldorf		Germany	40597
605	Novartis Investigative Site	Ebersbach		Germany	02730
606	Novartis Investigative Site	Elsterwerda		Germany	04910
607	Novartis Investigative Site	Erlangen		Germany	91054
608	Novartis Investigative Site	Essen		Germany	45136
609	Novartis Investigative Site	Essen		Germany	45276
610	Novartis Investigative Site	Essen		Germany	45355
611	Novartis Investigative Site	Falkensee		Germany	14612
612	Novartis Investigative Site	Frankfurt am Main		Germany	60313
613	Novartis Investigative Site	Frankfurt		Germany	60488
614	Novartis Investigative Site	Frankfurt		Germany	60594
615	Novartis Investigative Site	Freiburg		Germany	79106
616	Novartis Investigative Site	Fulda		Germany	36037
617	Novartis Investigative Site	Giengen		Germany	89537
618	Novartis Investigative Site	Goerlitz		Germany	02826
619	Novartis Investigative Site	Haag		Germany	83527
620	Novartis Investigative Site	Halle Saale		Germany	06120
621	Novartis Investigative Site	Hamburg		Germany	20246
622	Novartis Investigative Site	Hamburg		Germany	22041
623	Novartis Investigative Site	Hamburg		Germany	22177
624	Novartis Investigative Site	Hamburg		Germany	22393
625	Novartis Investigative Site	Hamburg		Germany	22765
626	Novartis Investigative Site	Heidelberg		Germany	69120
627	Novartis Investigative Site	Heilbronn		Germany	74078
628	Novartis Investigative Site	Huy / OT Anderbeck		Germany	38836
629	Novartis Investigative Site	Jerichow		Germany	39319
630	Novartis Investigative Site	Kallstadt		Germany	67169
631	Novartis Investigative Site	Kamp-Lintfort		Germany	47475
632	Novartis Investigative Site	Kassel		Germany	34127
633	Novartis Investigative Site	Kiel		Germany	24119
634	Novartis Investigative Site	Koblenz		Germany	56068
635	Novartis Investigative Site	Koeln		Germany	51065
636	Novartis Investigative Site	Kuenzing		Germany	94550
637	Novartis Investigative Site	Leipzig		Germany	04103
638	Novartis Investigative Site	Leipzig		Germany	04107
639	Novartis Investigative Site	Ludwigshafen		Germany	67063
640	Novartis Investigative Site	Lüneburg		Germany	21339
641	Novartis Investigative Site	Magdeburg		Germany	39112
642	Novartis Investigative Site	Mainz		Germany	55116
643	Novartis Investigative Site	Mainz		Germany	55131
644	Novartis Investigative Site	Mayen		Germany	56727
645	Novartis Investigative Site	Meissen		Germany	01662
646	Novartis Investigative Site	Meißen		Germany	01662
647	Novartis Investigative Site	Muehldorf Am Inn		Germany	84453
648	Novartis Investigative Site	Muehlhausen		Germany	99974
649	Novartis Investigative Site	Neuhofen		Germany	67141
650	Novartis Investigative Site	Neunkirchen		Germany	66539
651	Novartis Investigative Site	Northeim		Germany	37154
652	Novartis Investigative Site	Nurnberg		Germany	90402
653	Novartis Investigative Site	Oelde		Germany	59302
654	Novartis Investigative Site	Oschatz		Germany	04758
655	Novartis Investigative Site	Paderborn		Germany	33098
656	Novartis Investigative Site	Potsdam		Germany	14469
657	Novartis Investigative Site	Rednitzhembach		Germany	91126
658	Novartis Investigative Site	Reinfeld		Germany	23858
659	Novartis Investigative Site	Rostock		Germany	06120
660	Novartis Investigative Site	Rüdersdorf		Germany	15562
661	Novartis Investigative Site	Siegen		Germany	57072
662	Novartis Investigative Site	Ulm		Germany	89081
663	Novartis Investigative Site	Wolmirstedt		Germany	39326
664	Novartis Investigative Site	Athens	GR	Greece	14233
665	Novartis Investigative Site	Magoula	GR	Greece	190 18
666	Novartis Investigative Site	Thessaloniki	GR	Greece	564 03
667	Novartis Investigative Site	Thessaloniki	GR	Greece	570 10
668	Novartis Investigative Site	Voula	GR	Greece	166 73
669	Novartis Investigative Site	Athens		Greece	106 76
670	Novartis Investigative Site	Athens		Greece	115 27
671	Novartis Investigative Site	Athens		Greece	12462
672	Novartis Investigative Site	Chalkida		Greece	GR 341 00
673	Novartis Investigative Site	Crete Heraklion		Greece	714 09
674	Novartis Investigative Site	Heraklion Crete		Greece	711 10
675	Novartis Investigative Site	Patras		Greece	265 00
676	Novartis Investigative Site	Guatemala City		Guatemala	01001
677	Novartis Investigative Site	Guatemala City		Guatemala	01010
678	Novartis Investigative Site	Guatemala City		Guatemala	01011
679	Novartis Investigative Site	Guatemala City		Guatemala	01015
680	Novartis Investigative Site	Guatemala		Guatemala	01010
681	Novartis Investigative Site	Zalaegerszeg	Zala	Hungary	8900
682	Novartis Investigative Site	Budapest		Hungary	1042
683	Novartis Investigative Site	Budapest		Hungary	1083
684	Novartis Investigative Site	Budapest		Hungary	1122
685	Novartis Investigative Site	Budapest		Hungary	1125
686	Novartis Investigative Site	Budapest		Hungary	1134
687	Novartis Investigative Site	Budapest		Hungary	1145
688	Novartis Investigative Site	Budapest		Hungary	H-1115
689	Novartis Investigative Site	Csongrad		Hungary	6640
690	Novartis Investigative Site	Debrecen		Hungary	4032
691	Novartis Investigative Site	Gyula		Hungary	5700
692	Novartis Investigative Site	Kistarcsa		Hungary	2143
693	Novartis Investigative Site	Komarom		Hungary	2921
694	Novartis Investigative Site	Miskolc		Hungary	3530
695	Novartis Investigative Site	Mosonmagyarovar		Hungary	9200
696	Novartis Investigative Site	Nyiregyháza		Hungary	4400
697	Novartis Investigative Site	Pecs		Hungary	7623
698	Novartis Investigative Site	Szeged		Hungary	H 6725
699	Novartis Investigative Site	Szekesfehervar		Hungary	H-8000
700	Novartis Investigative Site	Szentes		Hungary	6600
701	Novartis Investigative Site	Kopavogur		Iceland	201
702	Novartis Investigative Site	Reykjavik		Iceland	IS-101
703	Novartis Investigative Site	Reykjavik		Iceland	IS-109
704	Novartis Investigative Site	Hyderabad	Andhra Pradesh	India	500001
705	Novartis Investigative Site	Hyderabad	Andhra Pradesh	India
706	Novartis Investigative Site	Nampally	Andhra Pradesh	India	500 001
707	Novartis Investigative Site	Nellore	Andhra Pradesh	India	524 003
708	Novartis Investigative Site	Tirupati	Andhra Pradesh	India	517 5-7
709	Novartis Investigative Site	Vijayawada	Andhra Pradesh	India	520 008
710	Novartis Investigative Site	Vijayawada	Andhra Pradesh	India	520010
711	Novartis Investigative Site	Vishakhapatnam	Andhra Pradesh	India	530 013
712	Novartis Investigative Site	Guntur	Andhrapradesh	India	522001
713	Novartis Investigative Site	New Delhi	Delhi	India	110060
714	Novartis Investigative Site	Ahmedabad	Gujarat	India	380 051
715	Novartis Investigative Site	Ahmedabad	Gujarat	India	380006
716	Novartis Investigative Site	Ahmedabad	Gujarat	India	380054
717	Novartis Investigative Site	Ahmedabad	Gujarat	India	382428
718	Novartis Investigative Site	Surat	Gujarat	India	395 002
719	Novartis Investigative Site	Surat	Gujarat	India	395001
720	Novartis Investigative Site	Vadodara	Gujarat	India	390015
721	Novartis Investigative Site	Bangalore	Karnataka	India	560 055
722	Novartis Investigative Site	Bengaluru	Karnataka	India	560034
723	Novartis Investigative Site	Manipal	Karnataka	India	576104
724	Novartis Investigative Site	Kochi	Kerala	India	682 018
725	Novartis Investigative Site	Nagpur	Maharashtra	India	400012
726	Novartis Investigative Site	Nagpur	Maharashtra	India	440 010
727	Novartis Investigative Site	Nagpur	Maharashtra	India	44000033
728	Novartis Investigative Site	Nagpur	Maharashtra	India	440012
729	Novartis Investigative Site	Nashik	Maharashtra	India	422 005
730	Novartis Investigative Site	Pune	Maharashtra	India	411004
731	Novartis Investigative Site	Pune	Maharashtra	India	411005
732	Novartis Investigative Site	Ludhiana	Punjab	India	141002
733	Novartis Investigative Site	Ludhiana	Punjab	India	141012
734	Novartis Investigative Site	Ludhiana	Punjab	India	141421
735	Novartis Investigative Site	Mohali	Punjab	India	160 062
736	Novartis Investigative Site	Bikaner	Rajasthan	India	334003
737	Novartis Investigative Site	Jaipur	Rajasthan	India	302016
738	Novartis Investigative Site	Jaipur	Rajasthan	India	302024
739	Novartis Investigative Site	Chennai	Tamil Nadu	India	600081
740	Novartis Investigative Site	Coimbatore	Tamil Nadu	India	641037
741	Novartis Investigative Site	Madurai	Tamil NADU	India	625107
742	Novartis Investigative Site	Coimbatore	Tamilnadu	India	641 018
743	Novartis Investigative Site	Hyderabad	Telangana	India	500 063
744	Novartis Investigative Site	Secunderabad	Telangana	India	500003
745	Novartis Investigative Site	Ghaziabad	Uttar Pradesh	India
746	Novartis Investigative Site	Lucknow	Uttar Pradesh	India	226005
747	Novartis Investigative Site	Varanasi	Uttar Pradesh	India	224105
748	Novartis Investigative Site	Ahmedabad		India	380025
749	Novartis Investigative Site	Rajasthan		India	324005
750	Novartis Investigative Site	Ancona	AN	Italy	60128
751	Novartis Investigative Site	Fermo	AP	Italy	63023
752	Novartis Investigative Site	Cortona	AR	Italy	52044
753	Novartis Investigative Site	Bergamo	BG	Italy	24127
754	Novartis Investigative Site	Treviglio	BG	Italy	24047
755	Novartis Investigative Site	Brescia	BS	Italy	25123
756	Novartis Investigative Site	Montichiari	BS	Italy	25018
757	Novartis Investigative Site	Monserrato	CA	Italy	09042
758	Novartis Investigative Site	Santa Maria Capua Vetere	CE	Italy	81055
759	Novartis Investigative Site	Chieti	CH	Italy	66100
760	Novartis Investigative Site	Catanzaro	CZ	Italy	88100
761	Novartis Investigative Site	Cona	FE	Italy	44100
762	Novartis Investigative Site	Foggia	FG	Italy	71100
763	Novartis Investigative Site	Firenze	FI	Italy	50134
764	Novartis Investigative Site	Pozzilli	IS	Italy	86077
765	Novartis Investigative Site	Milano	MI	Italy	20100
766	Novartis Investigative Site	Milano	MI	Italy	20132
767	Novartis Investigative Site	Milano	MI	Italy	20145
768	Novartis Investigative Site	Rozzano	MI	Italy	20089
769	Novartis Investigative Site	Massa	MS	Italy	54100
770	Novartis Investigative Site	Palermo	PA	Italy	90129
771	Novartis Investigative Site	Piacenza	PC	Italy	29100
772	Novartis Investigative Site	Pisa	PI	Italy	56126
773	Novartis Investigative Site	Parma	PR	Italy	43100
774	Novartis Investigative Site	Casorate Primo	PV	Italy	27022
775	Novartis Investigative Site	Pavia	PV	Italy	27100
776	Novartis Investigative Site	Roma	RM	Italy	00161
777	Novartis Investigative Site	Roma	RM	Italy	00168
778	Novartis Investigative Site	Roma	RM	Italy	00189
779	Novartis Investigative Site	Sassari	SS	Italy	07100
780	Novartis Investigative Site	Palmanova	UD	Italy	33057
781	Novartis Investigative Site	San Daniele Del Friuli	UD	Italy	33038
782	Novartis Investigative Site	Verona	VR	Italy	37134
783	Novartis Investigative Site	Soriano Calabro	VV	Italy	89831
784	Novartis Investigative Site	Napoli		Italy	80131
785	Novartis Investigative Site	Novara		Italy	28100
786	Novartis Investigative Site	Veruno		Italy	28010
787	Novartis Investigative Site	Ichinomiya	Aichi	Japan	491-8551
788	Novartis Investigative Site	Nagoya	Aichi	Japan	453-8511
789	Novartis Investigative Site	Seto-city	Aichi	Japan	489-8642
790	Novartis Investigative Site	Funabashi	Chiba	Japan	273-8588
791	Novartis Investigative Site	Matsudo city	Chiba	Japan	271 0077
792	Novartis Investigative Site	Matsudo-city	Chiba	Japan	270-2251
793	Novartis Investigative Site	Kasuga	Fukuoka	Japan	816-0864
794	Novartis Investigative Site	Kurume-city	Fukuoka	Japan	830-8577
795	Novartis Investigative Site	Onga-gun	Fukuoka	Japan	807-0051
796	Novartis Investigative Site	Yukuhashi	Fukuoka	Japan	824-0026
797	Novartis Investigative Site	Ogaki-city	Gifu	Japan	503-8502
798	Novartis Investigative Site	Fujioka city	Gunma	Japan	375-8503
799	Novartis Investigative Site	Takasaki-city	Gunma	Japan	370-0036
800	Novartis Investigative Site	Hatsukaichi city	Hiroshima	Japan	738 8503
801	Novartis Investigative Site	Amagasaki city	Hyogo	Japan	660 8550
802	Novartis Investigative Site	Amagasaki-city	Hyogo	Japan	661-0976
803	Novartis Investigative Site	Nishinomiya	Hyogo	Japan	663 8501
804	Novartis Investigative Site	Takarazuka-city	Hyogo	Japan	665-0022
805	Novartis Investigative Site	Higashiibaraki-gun	Ibaraki	Japan	311-3193
806	Novartis Investigative Site	Hitachi-city	Ibaraki	Japan	317-0077
807	Novartis Investigative Site	Sakaide-city	Kagawa	Japan	762-0007
808	Novartis Investigative Site	Takamatsu city	Kagawa	Japan	760 8557
809	Novartis Investigative Site	Yokohama	Kanagawa	Japan	234-0054
810	Novartis Investigative Site	Kumamoto City	Kumamoto	Japan	860-8556
811	Novartis Investigative Site	Kyoto-city	Kyoto	Japan	607-8062
812	Novartis Investigative Site	Sendai city	Miyagi	Japan	980 8574
813	Novartis Investigative Site	Sendai-shi	Miyagi	Japan	983 8520
814	Novartis Investigative Site	Nagano City	Nagano	Japan	380 0814
815	Novartis Investigative Site	Hirakata-City	Osaka	Japan	573-0153
816	Novartis Investigative Site	Osaka-city	Osaka	Japan	543-0035
817	Novartis Investigative Site	Osaka-city	Osaka	Japan	543-8555
818	Novartis Investigative Site	Osaka-city	Osaka	Japan	558-8558
819	Novartis Investigative Site	Takatsuki	Osaka	Japan	569-0852
820	Novartis Investigative Site	Sayama-city	Saitama	Japan	350-1305
821	Novartis Investigative Site	Tokorozawa	Saitama	Japan	359-1142
822	Novartis Investigative Site	Kusatsu-city	Shiga	Japan	525-0014
823	Novartis Investigative Site	Komatsushima-city	Tokushima	Japan	773-8502
824	Novartis Investigative Site	Bunkyo-ku	Tokyo	Japan	113-8603
825	Novartis Investigative Site	Chiyoda-ku	Tokyo	Japan	101-8309
826	Novartis Investigative Site	Chiyoda-ku	Tokyo	Japan	101-8643
827	Novartis Investigative Site	Fuchu-city	Tokyo	Japan	183-0003
828	Novartis Investigative Site	Itabashi-ku	Tokyo	Japan	173-8610
829	Novartis Investigative Site	Wonju	Gangwon-Do	Korea, Republic of	26426
830	Novartis Investigative Site	Suwon	Gyeonggi-do	Korea, Republic of	443380
831	Novartis Investigative Site	Uijeongbu-Si	Gyeonggi-do	Korea, Republic of	480-717
832	Novartis Investigative Site	Daejeon	Korea	Korea, Republic of	35015
833	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	08308
834	Novartis Investigative Site	Seoul	Seocho Gu	Korea, Republic of	06591
835	Novartis Investigative Site	Busan		Korea, Republic of	49201
836	Novartis Investigative Site	Busan		Korea, Republic of	602739
837	Novartis Investigative Site	Busan		Korea, Republic of	612-896
838	Novartis Investigative Site	Daegu		Korea, Republic of	705 718
839	Novartis Investigative Site	Daegu		Korea, Republic of	705703
840	Novartis Investigative Site	Gwangju		Korea, Republic of	61469
841	Novartis Investigative Site	Seoul		Korea, Republic of	03722
842	Novartis Investigative Site	Liepaja	LV	Latvia	LV-3414
843	Novartis Investigative Site	Riga	LV	Latvia	LV-1005
844	Novartis Investigative Site	Ventspils	LV	Latvia	LV-3601
845	Novartis Investigative Site	Daugavpils		Latvia	LV-5417
846	Novartis Investigative Site	Riga		Latvia	1012
847	Novartis Investigative Site	Valmiera		Latvia	4201
848	Novartis Investigative Site	Kaunas	LTU	Lithuania	LT 50161
849	Novartis Investigative Site	Klaipeda	LTU	Lithuania	LT-92288
850	Novartis Investigative Site	Alytus		Lithuania	LT-62386
851	Novartis Investigative Site	Kaunas		Lithuania	LT-44320
852	Novartis Investigative Site	Kaunas		Lithuania	LT-49387
853	Novartis Investigative Site	Kaunas		Lithuania	LT-49449
854	Novartis Investigative Site	Kedainiai		Lithuania	LT-57164
855	Novartis Investigative Site	Panevezys		Lithuania	LT-37460
856	Novartis Investigative Site	Siauliai		Lithuania	LT-76231
857	Novartis Investigative Site	Vilnius		Lithuania	LT-08661
858	Novartis Investigative Site	Guadalajara	Jalisco	Mexico	44210
859	Novartis Investigative Site	Guadalajara	Jalisco	Mexico	44280
860	Novartis Investigative Site	San Luis Potosi	San Luis Potosí	Mexico	78240
861	Novartis Investigative Site	Culiacan	Sinaloa	Mexico	80230
862	Novartis Investigative Site	Aguascalientes		Mexico	20230
863	Novartis Investigative Site	Queretaro		Mexico	76000
864	Novartis Investigative Site	San Luis Potosi		Mexico	78200
865	Novartis Investigative Site	Maastricht	AZ	Netherlands	5800
866	Novartis Investigative Site	Apeldoorn	DZ	Netherlands	7334
867	Novartis Investigative Site	Sneek	The Netherlands	Netherlands	8601 ZR
868	Novartis Investigative Site	Alkmaar		Netherlands	1815 JD
869	Novartis Investigative Site	Amersfoort		Netherlands	3813 TZ
870	Novartis Investigative Site	Amstelveen		Netherlands	1186 AM
871	Novartis Investigative Site	Amsterdam		Netherlands	1090 HM
872	Novartis Investigative Site	Amsterdam		Netherlands	1105 AZ
873	Novartis Investigative Site	Breda		Netherlands	4811SW
874	Novartis Investigative Site	Deventer		Netherlands	7416 SE
875	Novartis Investigative Site	Doetinchem		Netherlands	7009 BL
876	Novartis Investigative Site	Ede		Netherlands	6716 RP
877	Novartis Investigative Site	Gouda		Netherlands	2803 HH
878	Novartis Investigative Site	Groningen		Netherlands	NL-9711 SG
879	Novartis Investigative Site	Haarlem		Netherlands	2035 RC
880	Novartis Investigative Site	Heerlen		Netherlands	6419 PC
881	Novartis Investigative Site	Hoorn		Netherlands	1624 NP
882	Novartis Investigative Site	Leeuwarden		Netherlands	8934 AD
883	Novartis Investigative Site	Meppel		Netherlands	7943 KA
884	Novartis Investigative Site	Nijmegen		Netherlands
885	Novartis Investigative Site	Rotterdam		Netherlands	3001 HG
886	Novartis Investigative Site	Rotterdam		Netherlands	3083 AN
887	Novartis Investigative Site	Tiel		Netherlands	4002 WP
888	Novartis Investigative Site	Utrecht		Netherlands	3584 CX
889	Novartis Investigative Site	Venlo		Netherlands	5912 BL
890	Novartis Investigative Site	Alesund		Norway	NO-6026
891	Novartis Investigative Site	Elverum		Norway	2408
892	Novartis Investigative Site	Hamar		Norway	2317
893	Novartis Investigative Site	Harstad		Norway	9481
894	Novartis Investigative Site	Hønefoss		Norway	3501
895	Novartis Investigative Site	Lillehammer		Norway	2629
896	Novartis Investigative Site	Moss		Norway	1523
897	Novartis Investigative Site	Nesttun		Norway	5221
898	Novartis Investigative Site	Oslo		Norway	0303
899	Novartis Investigative Site	Oslo		Norway	0424
900	Novartis Investigative Site	Sandefjord		Norway	3211
901	Novartis Investigative Site	Skedsmokorset		Norway	2020
902	Novartis Investigative Site	Stavanger		Norway	4068
903	Novartis Investigative Site	Tonsberg		Norway	3116
904	Novartis Investigative Site	Trondheim		Norway	7011
905	Novartis Investigative Site	Tynset		Norway	2501
906	Novartis Investigative Site	Bellavista	Lima	Peru	CALLAO 02
907	Novartis Investigative Site	San Isidro	Lima	Peru	27
908	Novartis Investigative Site	San Martin de Porres	Lima	Peru	31
909	Novartis Investigative Site	Lima		Peru	LIMA 39
910	Novartis Investigative Site	Gdansk		Poland	80-435
911	Novartis Investigative Site	Gdynia		Poland	81-157
912	Novartis Investigative Site	Gdynia		Poland	81-302
913	Novartis Investigative Site	Gdynia		Poland	81-423
914	Novartis Investigative Site	Lublin		Poland	20-538
915	Novartis Investigative Site	Olawa		Poland	55-200
916	Novartis Investigative Site	Ostrow Wielkopolski		Poland	63-400
917	Novartis Investigative Site	Poznan		Poland	60-375
918	Novartis Investigative Site	Poznan		Poland	61-874
919	Novartis Investigative Site	Pulawy		Poland	24100
920	Novartis Investigative Site	Rumia		Poland	84-230
921	Novartis Investigative Site	Skierniewice		Poland	96-100
922	Novartis Investigative Site	Torun		Poland	87-100
923	Novartis Investigative Site	Warszawa		Poland	04-073
924	Novartis Investigative Site	Wegrow		Poland	07-100
925	Novartis Investigative Site	Wloclawek		Poland	87-800
926	Novartis Investigative Site	Manati		Puerto Rico	00674
927	Novartis Investigative Site	Mayaguez		Puerto Rico	00680
928	Novartis Investigative Site	Ponce		Puerto Rico	00716
929	Novartis Investigative Site	Ponce		Puerto Rico	00717
930	Novartis Investigative Site	San Juan		Puerto Rico	00909
931	Novartis Investigative Site	San Juan		Puerto Rico	00926
932	Novartis Investigative Site	San Juan		Puerto Rico	00936-6528
933	Novartis Investigative Site	Pitesti	Arges	Romania	110438
934	Novartis Investigative Site	Bucharest	District 1	Romania
935	Novartis Investigative Site	Bucuresti	District 1	Romania	010225
936	Novartis Investigative Site	Bucharest	District 2	Romania
937	Novartis Investigative Site	Bucuresti	District 4	Romania	4204179
938	Novartis Investigative Site	Oradea	Jud Bihor	Romania	410169
939	Novartis Investigative Site	Cluj Napoca	Jud Cluj	Romania	400015
940	Novartis Investigative Site	Iasi	Jud Iasi	Romania	700732
941	Novartis Investigative Site	Targu Mures	Jud Mures	Romania	540043
942	Novartis Investigative Site	Constanta	Jud. Constanta	Romania	900591
943	Novartis Investigative Site	Craiova	Jud. Dolj	Romania	200497
944	Novartis Investigative Site	Iasi	Jud. Iasi	Romania	700111
945	Novartis Investigative Site	Targu Mures	Mures	Romania	540124
946	Novartis Investigative Site	Tg Mures	Mures	Romania	540136
947	Novartis Investigative Site	Braila	ROM	Romania	810249
948	Novartis Investigative Site	Timisoara	Timis	Romania	300362
949	Novartis Investigative Site	Baia Mare		Romania	430123
950	Novartis Investigative Site	Brasov		Romania	500283
951	Novartis Investigative Site	Bucharest		Romania	021659
952	Novartis Investigative Site	Bucuresti		Romania	011728
953	Novartis Investigative Site	Bucuresti		Romania	011774
954	Novartis Investigative Site	Cluj Napoca		Romania	400006
955	Novartis Investigative Site	Cluj-Napoca		Romania	400347
956	Novartis Investigative Site	Craiova		Romania	200642
957	Novartis Investigative Site	Oradea		Romania	410169
958	Novartis Investigative Site	Pitesti		Romania	110084
959	Novartis Investigative Site	Sibiu		Romania	550371
960	Novartis Investigative Site	Targu Mures		Romania	540096
961	Novartis Investigative Site	Targu Mures		Romania	540142
962	Novartis Investigative Site	Targu-Mures		Romania	540136
963	Novartis Investigative Site	Timisoara		Romania	300310
964	Novartis Investigative Site	Timisoara		Romania	300736
965	Novartis Investigative Site	Chelyabinsk		Russian Federation	454000
966	Novartis Investigative Site	Chelyabinsk		Russian Federation	454047
967	Novartis Investigative Site	Chelyabinsk		Russian Federation	454048
968	Novartis Investigative Site	Ekaterinburg		Russian Federation	620028
969	Novartis Investigative Site	Ekaterinburg		Russian Federation	620102
970	Novartis Investigative Site	Ekaterinburg		Russian Federation	620137
971	Novartis Investigative Site	Izhevsk		Russian Federation	426063
972	Novartis Investigative Site	Kazan		Russian Federation	420012
973	Novartis Investigative Site	Kemerovo		Russian Federation	650029
974	Novartis Investigative Site	Kirov		Russian Federation	610027
975	Novartis Investigative Site	Kirov		Russian Federation	610035
976	Novartis Investigative Site	Krasnodar		Russian Federation	350086
977	Novartis Investigative Site	Moscow		Russian Federation	111539
978	Novartis Investigative Site	Moscow		Russian Federation	117198
979	Novartis Investigative Site	Moscow		Russian Federation	117556
980	Novartis Investigative Site	Moscow		Russian Federation	119881
981	Novartis Investigative Site	Moscow		Russian Federation	125284
982	Novartis Investigative Site	Moscow		Russian Federation	127018
983	Novartis Investigative Site	Moscow		Russian Federation	127473
984	Novartis Investigative Site	Novosibirsk		Russian Federation	630087
985	Novartis Investigative Site	Penza		Russian Federation	440067
986	Novartis Investigative Site	Perm		Russian Federation	614097
987	Novartis Investigative Site	Perm		Russian Federation	614107
988	Novartis Investigative Site	Petrozavodsk		Russian Federation	185019
989	Novartis Investigative Site	Ryazan		Russian Federation	390026
990	Novartis Investigative Site	Saint Petersburg		Russian Federation	195067
991	Novartis Investigative Site	Saint Petersburg		Russian Federation	197022
992	Novartis Investigative Site	Saint Petersburg		Russian Federation	197341
993	Novartis Investigative Site	Saint Petersburg		Russian Federation	199106
994	Novartis Investigative Site	Saint-Petersburg		Russian Federation	192257
995	Novartis Investigative Site	Saint-Petersburg		Russian Federation	194044
996	Novartis Investigative Site	Samara		Russian Federation	443070
997	Novartis Investigative Site	Samara		Russian Federation	443096
998	Novartis Investigative Site	Saratov		Russian Federation	410012
999	Novartis Investigative Site	Saratov		Russian Federation	410028
1000	Novartis Investigative Site	Sestroretsk		Russian Federation	197706
1001	Novartis Investigative Site	Smolensk		Russian Federation	214018
1002	Novartis Investigative Site	St-Petersburg		Russian Federation	194295
1003	Novartis Investigative Site	St-Petersburg		Russian Federation	196084
1004	Novartis Investigative Site	St. Petersburg		Russian Federation	190013
1005	Novartis Investigative Site	St.- Petersburg		Russian Federation	197110
1006	Novartis Investigative Site	St.Petersburg		Russian Federation	193163
1007	Novartis Investigative Site	Syktyvkar		Russian Federation	167981
1008	Novartis Investigative Site	Tomsk		Russian Federation	634012
1009	Novartis Investigative Site	Tyumen		Russian Federation	625026
1010	Novartis Investigative Site	Vladimir		Russian Federation	600020
1011	Novartis Investigative Site	Yaroslavl		Russian Federation	150047
1012	Novartis Investigative Site	Yekaterinburg		Russian Federation	620109
1013	Novartis Investigative Site	Beograd		Serbia	11040
1014	Novartis Investigative Site	Niska Banja		Serbia	18205
1015	Novartis Investigative Site	Nis		Serbia	18000
1016	Novartis Investigative Site	Sremska Kamenica		Serbia	21204
1017	Novartis Investigative Site	Bratislava	Slovak Republic	Slovakia	826 06
1018	Novartis Investigative Site	Brezno	Slovak Republic	Slovakia	977 42
1019	Novartis Investigative Site	Komarno	Slovak Republic	Slovakia	94575
1020	Novartis Investigative Site	Kosice	Slovak Republic	Slovakia	040 22
1021	Novartis Investigative Site	Povazska Bystrica	Slovak Republic	Slovakia	017 01
1022	Novartis Investigative Site	Presov	Slovak Republic	Slovakia	080 01
1023	Novartis Investigative Site	Presov	Slovak Republic	Slovakia	08001
1024	Novartis Investigative Site	Rimavska Sobota	Slovak Republic	Slovakia	97901
1025	Novartis Investigative Site	Svidnik	Slovak Republic	Slovakia	08901
1026	Novartis Investigative Site	Velky Krtis	Slovak Republic	Slovakia	990 01
1027	Novartis Investigative Site	Banska Bystrica		Slovakia	97401
1028	Novartis Investigative Site	Bardejov		Slovakia	085 01
1029	Novartis Investigative Site	Bratislava		Slovakia	81369
1030	Novartis Investigative Site	Bratislava		Slovakia	831 06
1031	Novartis Investigative Site	Bratislava		Slovakia	841 07
1032	Novartis Investigative Site	Dubnica nad Vahom		Slovakia	01841
1033	Novartis Investigative Site	Dunajska Streda		Slovakia	929 01
1034	Novartis Investigative Site	Galanta		Slovakia	92701
1035	Novartis Investigative Site	Kosice		Slovakia	040 01
1036	Novartis Investigative Site	Kosice		Slovakia	04001
1037	Novartis Investigative Site	Levice		Slovakia	934 01
1038	Novartis Investigative Site	Lucenec		Slovakia	984 01
1039	Novartis Investigative Site	Lucenec		Slovakia	98403
1040	Novartis Investigative Site	Martin		Slovakia	036 01
1041	Novartis Investigative Site	Nitra		Slovakia	949 01
1042	Novartis Investigative Site	Nitra		Slovakia	94901
1043	Novartis Investigative Site	Nove Zamky		Slovakia	940 01
1044	Novartis Investigative Site	Nove Zamky		Slovakia	94002
1045	Novartis Investigative Site	Presov		Slovakia	081 01
1046	Novartis Investigative Site	Trnava		Slovakia	91702
1047	Novartis Investigative Site	Zilina		Slovakia	012 07
1048	Novartis Investigative Site	Celje		Slovenia	3000
1049	Novartis Investigative Site	Golnik		Slovenia	4204
1050	Novartis Investigative Site	Ljubljana		Slovenia	1000
1051	Novartis Investigative Site	Durban	Kwa-Zulu Natal	South Africa	4052
1052	Novartis Investigative Site	Cape Town	Western Cape	South Africa	7405
1053	Novartis Investigative Site	Alberton		South Africa	1449
1054	Novartis Investigative Site	Bloemfontein		South Africa	9301
1055	Novartis Investigative Site	Cape Town		South Africa	7405
1056	Novartis Investigative Site	Cape Town		South Africa	7925
1057	Novartis Investigative Site	Centurion		South Africa	4001
1058	Novartis Investigative Site	Johannesburg		South Africa	2193
1059	Novartis Investigative Site	Kempton Park		South Africa	1620
1060	Novartis Investigative Site	Pretoria		South Africa	0002
1061	Novartis Investigative Site	Western Cape		South Africa	7130
1062	Novartis Investigative Site	Göteborg	Vastra Gotalands Lan	Sweden	SE-413 45
1063	Novartis Investigative Site	Boras		Sweden	506 30
1064	Novartis Investigative Site	Goteborg		Sweden	416 85
1065	Novartis Investigative Site	Kristianstad		Sweden	291 85
1066	Novartis Investigative Site	Luleå		Sweden	972 33
1067	Novartis Investigative Site	Lund		Sweden	22142
1068	Novartis Investigative Site	Lund		Sweden	222 21
1069	Novartis Investigative Site	Malmö		Sweden	214 22
1070	Novartis Investigative Site	Molndal		Sweden	431 80
1071	Novartis Investigative Site	Skanör		Sweden	239 33
1072	Novartis Investigative Site	Skelleftea		Sweden	931 86
1073	Novartis Investigative Site	Stockholm		Sweden	118 83
1074	Novartis Investigative Site	Stockholm		Sweden	SE-111 35
1075	Novartis Investigative Site	Uddevalla		Sweden	451 50
1076	Novartis Investigative Site	Vallingby		Sweden	162 68
1077	Novartis Investigative Site	Vasteras		Sweden	72189
1078	Novartis Investigative Site	Östersund		Sweden	831 83
1079	Novartis Investigative Site	Taichung	Taiwan ROC	Taiwan	40201
1080	Novartis Investigative Site	Taipei	Taiwan, ROC	Taiwan	11217
1081	Novartis Investigative Site	Changhua		Taiwan	50006
1082	Novartis Investigative Site	Kaohsiung City		Taiwan	83301
1083	Novartis Investigative Site	Kaohsiung		Taiwan	80756
1084	Novartis Investigative Site	Taichung		Taiwan	40447
1085	Novartis Investigative Site	Tainan		Taiwan	71004
1086	Novartis Investigative Site	Taipei		Taiwan	10002
1087	Novartis Investigative Site	Taipei		Taiwan	10449
1088	Novartis Investigative Site	Taipei		Taiwan	114
1089	Novartis Investigative Site	Taipei		Taiwan
1090	Novartis Investigative Site	Taoyuan		Taiwan	33305
1091	Novartis Investigative Site	Yilan		Taiwan	26058
1092	Novartis Investigative Site	Eskisehir	Meselik	Turkey	26480
1093	Novartis Investigative Site	Aydin		Turkey	09100
1094	Novartis Investigative Site	Istanbul		Turkey	34304
1095	Novartis Investigative Site	Izmir		Turkey	35040
1096	Novartis Investigative Site	Izmir		Turkey	35340
1097	Novartis Investigative Site	Kocaeli		Turkey	41380
1098	Novartis Investigative Site	Mersin		Turkey	33079
1099	Novartis Investigative Site	Sivas		Turkey	58140
1100	Novartis Investigative Site	Basingstoke	Hampshire	United Kingdom	RG24 9NA
1101	Novartis Investigative Site	Newport	Isle Of Wight	United Kingdom	PO30 5TG
1102	Novartis Investigative Site	Salford	Manchester	United Kingdom	M6 8HD
1103	Novartis Investigative Site	Whitby	North Yorkshire	United Kingdom	Y021 1SD
1104	Novartis Investigative Site	Dundee	Perthshire	United Kingdom	DD1 9SY
1105	Novartis Investigative Site	Axbridge	Somerset	United Kingdom	BS26 2BJ
1106	Novartis Investigative Site	Taunton	Somerset	United Kingdom	TA1 5DA
1107	Novartis Investigative Site	Cardiff	Wales	United Kingdom	CF5 4AD
1108	Novartis Investigative Site	Barnet		United Kingdom	EN5 3DJ
1109	Novartis Investigative Site	Berkshire		United Kingdom	RG2 0TG
1110	Novartis Investigative Site	Birmingham		United Kingdom	B15 2SQ
1111	Novartis Investigative Site	Birmingham		United Kingdom	B15 2TH
1112	Novartis Investigative Site	Birmingham		United Kingdom	B9 5SS
1113	Novartis Investigative Site	Cardiff		United Kingdom	CF14 5GJ
1114	Novartis Investigative Site	Cheshire		United Kingdom	CW11 1EQ
1115	Novartis Investigative Site	Chesterfield		United Kingdom	S40 4AA
1116	Novartis Investigative Site	Chorley		United Kingdom	PR7 7NA
1117	Novartis Investigative Site	Exeter		United Kingdom	EX2 5DW
1118	Novartis Investigative Site	Glasgow		United Kingdom	G20 0SP
1119	Novartis Investigative Site	Glasgow		United Kingdom	G20 0XA
1120	Novartis Investigative Site	Glasgow		United Kingdom	G51 4TF
1121	Novartis Investigative Site	Irvine		United Kingdom	KA12 0AY
1122	Novartis Investigative Site	Leicester		United Kingdom	LE3 9QP
1123	Novartis Investigative Site	Liverpool		United Kingdom	L22 0LG
1124	Novartis Investigative Site	London		United Kingdom	EC14 7BE
1125	Novartis Investigative Site	Manchester		United Kingdom	M15 6SX
1126	Novartis Investigative Site	Newcastle Upon Tyne		United Kingdom	NE7 7DN
1127	Novartis Investigative Site	Newport		United Kingdom	NP20 2UB
1128	Novartis Investigative Site	Norwich		United Kingdom	NR4 7UY
1129	Novartis Investigative Site	Nottingham		United Kingdom	NG5 1PB
1130	Novartis Investigative Site	Sheffield		United Kingdom	S5 7AU
1131	Novartis Investigative Site	Wiltshire		United Kingdom	SN15 2SB
1132	Novartis Investigative Site	Worcester		United Kingdom	WR5 1DD
1133	Novartis Investigative Site	York		United Kingdom	YO31 8HE

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT01327846

Other Study ID Numbers:

CACZ885M2301
2010-022970-14

First Posted:

Apr 4, 2011

Last Update Posted:

Jan 22, 2020

Last Verified:

Jan 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Novartis Pharmaceuticals

Cardiovascular Death

Myocardial Infarction

Additional relevant MeSH terms:

Atherosclerosis

Study Results

Participant Flow

Recruitment Details	10066 patients enrolled in the Core phase (4 randomized groups); 5 patients enrolled in the safety set were not included in efficacy set. 5777 patients continued in the Extension phase (539 entered only the washout period, 5238 entered the treatment period(s)). The Core phase completed as planned; "terminated" applies to the Extension phase.
Pre-assignment Detail	A total of 17482 patients were screened, and 10102 patients completed the screening phase. A total of 6430 patients did not complete the screening phase due to screen failure.

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Period Title: Core Phase
STARTED	2263	2284	2170	3344
COMPLETED	2235	2252	2144	3311
NOT COMPLETED	28	32	26	33
Period Title: Core Phase
STARTED	1267	1287	1279	1944
Stopped/Discontinued Study at Washout	127	97	137	178
Completed Treatment Period	41	45	49	60
Details Missing	0	1	1	0
COMPLETED	168	143	187	238
NOT COMPLETED	1099	1144	1092	1706

Baseline Characteristics

Arm/Group Title	Group I	Group II	Group III	Group IV	Total
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Total of all reporting groups
Overall Participants	2263	2284	2170	3344	10061
Age, Customized (Number) [Number]
< 65	1424 62.9%	1428 62.5%	1350 62.2%	2089 62.5%	6291 62.5%
>= 65	839 37.1%	856 37.5%	820 37.8%	1255 37.5%	3770 37.5%
Sex: Female, Male (Count of Participants)
Female	606 26.8%	575 25.2%	541 24.9%	865 25.9%	2587 25.7%
Male	1657 73.2%	1709 74.8%	1629 75.1%	2479 74.1%	7474 74.3%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	1804 79.7%	1808 79.2%	1772 81.7%	2652 79.3%	8036 79.9%
Black	84 3.7%	67 2.9%	61 2.8%	106 3.2%	318 3.2%
Asian	265 11.7%	278 12.2%	232 10.7%	388 11.6%	1163 11.6%
Native American	47 2.1%	49 2.1%	41 1.9%	82 2.5%	219 2.2%
Pacific Islander	0 0%	0 0%	1 0%	1 0%	2 0%
Unknown	3 0.1%	3 0.1%	1 0%	3 0.1%	10 0.1%
Other	60 2.7%	79 3.5%	62 2.9%	112 3.3%	313 3.1%

Outcome Measures

1. Primary Outcome

Title	Analysis of Core Phase First CEC Confirmed Major Adverse Cardiovascular Events (MACE) and Its Components
Description	Time to occurrence of CEC (Cardiovascular clinical events adjudication committee) confirmed MACE, which was a composite endpoint consisting of CEC confirmed CV death, CEC confirmed non-fatal MI,or CEC confirmed non-fatal stroke. Patients with the CEC adjudicated reason for death of "Unknown" were counted as CV (cardiovascular) death.
Time Frame	From randomization, to end of treatment plus 30 days, up to approximately 6 years

Outcome Measure Data

Analysis Population Description
Full Analysis Set (FAS): All randomized patients except for those who were misrandomized or from sites with serious GCP violations

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	2263	2284	2170	3344
MACE	322 14.2%	320 14%	313 14.4%	535 16%
CV death	151 6.7%	144 6.3%	137 6.3%	235 7%
MI (fatal and non-fatal)	174 7.7%	159 7%	169 7.8%	292 8.7%
MI (non-fatal)	171 7.6%	158 6.9%	168 7.7%	291 8.7%
Stroke (fatal and non-fatal)	51 2.3%	63 2.8%	58 2.7%	92 2.8%
Stroke (non-fatal)	51 2.3%	63 2.8%	58 2.7%	91 2.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I, Group IV
	Comments	H11: The hazard rate of first adjudication committee confirmed MACE in the canakinumab 300 mg dose group is greater than or equal to the hazard rate of the placebo group
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.0648
	Comments	1-sided adjusted for multiplicity using weighted Dunnett test. [significance level 0.0245]
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95% 0.75 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	MACE

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group II, Group IV
	Comments	H21: The hazard rate of first adjudication committee confirmed MACE in the canakinumab 150 mg dose group is greater than or equal to the hazard rate of the placebo group
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.0241
	Comments	1-sided adjusted for multiplicity using weighted Dunnett test. [significance level 0.0245]
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95% 0.74 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	MACE

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group III, Group IV
	Comments	H31: The hazard rate of first adjudication committee confirmed MACE in the canakinumab 50 mg dose group is greater than or equal to the hazard rate of the placebo group.
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.1895
	Comments	1-sided adjusted for multiplicity using weighted Dunnett test. [significance level 0.0245]
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95% 0.80 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	MACE

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Group I, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.572
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95% 0.77 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	CV death

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Group II, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.296
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95% 0.73 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	CV death

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Group III, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.369
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95% 0.73 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	CV death

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Group I, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.067
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95% 0.69 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	MI (fatal and non-fatal)

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Group II, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.006
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95% 0.63 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	MI (fatal and non-fatal)

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Group III, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.542
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95% 0.78 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	MI (fatal and non-fatal)

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Group I, Group IV
	Comments
	Type of Statistical Test	Other
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95% 0.68 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	MI (non-fatal)

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Group II, Group IV
	Comments
	Type of Statistical Test	Other
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95% 0.62 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	MI (non-fatal)

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Group III, Group IV
	Comments
	Type of Statistical Test	Other
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95% 0.78 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	MI (non-fatal)

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Group I, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.190
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95% 0.56 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stroke (fatal and non-fatal)

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Group II, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.912
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95% 0.71 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stroke (fatal and non-fatal)

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Group III, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.871
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95% 0.74 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stroke (fatal and non-fatal)

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Group I, Group IV
	Comments
	Type of Statistical Test	Other
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95% 0.57 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stroke (nonfatal)

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Group II, Group IV
	Comments
	Type of Statistical Test	Other
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95% 0.72 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stroke (nonfatal)

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Group III, Group IV
	Comments
	Type of Statistical Test	Other
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95% 0.75 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stroke (nonfatal)

2. Primary Outcome

Title	Substudy 1 (Core Phase): Change From Baseline in Carotid Plaque Burden in the Bifurcation Region of the Index Carotid Artery
Description
Time Frame	24 months

Outcome Measure Data

Analysis Population Description
Data from subjects were not collected as the substudy was terminated prior to data collection.

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	0	0	0	0

3. Primary Outcome

Title	Substudy 2 (Core Phase): Change From Baseline of the Insulin Secretion Rate (ISR) Relative to Glucose 0-30 Min Defined as Φ30 = AUCISR 0-30 / AUCGluc 0-30 Averaged Across the Year 3, 4, 5 Visits
Description
Time Frame	From randomization up to approximately 6 years

Outcome Measure Data

Analysis Population Description
Data from subjects were not collected as the substudy was terminated prior to data collection.

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	0	0	0	0

4. Secondary Outcome

Title	Patients With Core Phase CEC Confirmed CV Death, Non-fatal MI, Non-fatal Stroke, or Hospitalization for Unstable Angina Requiring Unplanned Revascularization
Description	Occurrence of the composite cardiovascular endpoint consisting of cardiovascular death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina requiring unplanned revascularization. MACE includes CV death, non-fatal MI and non-fatal stroke. CEC = Clinical Endpoints Committee
Time Frame	From randomization, to end of treatment pus 30 days, up to approximately 6 years

Outcome Measure Data

Analysis Population Description
FAS: All randomized patients except for those who were misrandomized or from sites with serious GCP violations

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	2263	2284	2170	3344
MACE or unstable angina	348 15.4%	352 15.4%	344 15.9%	601 18%
Unstable angina	34 1.5%	38 1.7%	38 1.8%	85 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.0648
	Comments	1-sided adjusted for multiplicity using weighted Dunnett test. [significance level 0.0245]
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95% 0.72 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	MACE or unstable angina

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group II, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.0241
	Comments	1-sided adjusted for multiplicity using weighted Dunnett test. [significance level 0.0245]
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95% 0.73 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	MACE or unstable angina

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group III, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.1895
	Comments	1-sided adjusted for multiplicity using weighted Dunnett test. [significance level 0.0245]
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95% 0.79 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	MACE or unstable angina

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Group I, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.007
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95% 0.39 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	unstable angina

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Group II, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.022
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95% 0.44 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	unstable angina

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Group III, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.086
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95% 0.48 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	unstable angina

5. Secondary Outcome

Title	Patients With Core Phase New Onset Type 2 Diabetes Among Patients With Pre-diabetes at Randomization
Description	Time to CEC confirmed new onset of type 2 diabetes among those with pre-diabetes at randomization (i.e. excluding those that are normoglycemic at baseline)
Time Frame	From randomization up to approximately 6 years

Outcome Measure Data

Analysis Population Description
FAS: All randomized patients except for those who were misrandomized or from sites with serious GCP violations

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	1132	1094	1089	1645
Number [Participants]	169 7.5%	171 7.5%	161 7.4%	246 7.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.8456
	Comments	1-sided adjusted for multiplicity using weighted Dunnett test. [significance level 0.0245]
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95% 0.83 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group II, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.8456
	Comments	1-sided adjusted for multiplicity using weighted Dunnett test. [significance level 0.0245]
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95% 0.87 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group III, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.6541
	Comments	1-sided adjusted for multiplicity using weighted Dunnett test. [significance level 0.0245]
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95% 0.80 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Core Phase All-cause Mortality, Non-fatal MI, or Non-fatal Stroke
Description	Occurrence of the composite endpoint consisting of all-cause mortality, non-fatal IM, or non-fatal stroke
Time Frame	From randomization, to end of treatment plus 30 days, up to approximately 6 years

Outcome Measure Data

Analysis Population Description
FAS: All randomized patients except for those who were misrandomized or from sites with serious GCP violations

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	2263	2284	2170	3344
Number [Participants]	403 17.8%	395 17.3%	394 18.2%	661 19.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.028
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95% 0.77 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	All-cause mortality or MI or Stroke

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group II, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.011
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95% 0.75 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	All-cause mortality or MI or Stroke

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group III, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.377
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95% 0.83 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	All-cause mortality or MI or Stroke

7. Secondary Outcome

Title	Core Phase All-cause Mortality
Description	Number of participant deaths
Time Frame	From randomization, to end of treatment plus 30 days, up to approximately 6 years

Outcome Measure Data

Analysis Population Description
FAS: All randomized patients except for those who were misrandomized or from sites with serious GCP violations

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	2263	2284	2170	3344
Number [Participants]	239 10.6%	238 10.4%	228 10.5%	375 11.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.406
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95% 0.79 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	All-cause mortality

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group II, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.329
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95% 0.78 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	All-cause mortality

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Group III, Group IV
	Comments
	Type of Statistical Test	Superiority
	Comments	A HR < 1 favors Canakinumab

Statistical Test of Hypothesis	p-Value	0.597
	Comments	2-sided unadjusted p-value
	Method	Regression, Cox
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95% 0.81 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	All-cause mortality

8. Secondary Outcome

Title	Summary of Adverse Events (Core Phase)
Description	Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs) occurring during the double-blind Core phase of the study. AEs/SAEs are any signs or symptoms that occur during the study treatment.
Time Frame	From randomization, to end of treatment plus 30 days, up to approximately 6 years

Outcome Measure Data

Analysis Population Description
Safety set: All patients who received at least one dose of study treatment and had at least one post-baseline safety assessment

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	2263	2285	2170	3348
Patients with at least one AE	1987 87.8%	1970 86.3%	1872 86.3%	2915 87.2%
AEs suspected to be related tostudy drug	355 15.7%	350 15.3%	267 12.3%	474 14.2%
Patients with at least one SAE	836 36.9%	812 35.6%	741 34.1%	1204 36%
Discontinued due to SAEs	135 6%	130 5.7%	117 5.4%	198 5.9%
Discontinued due to non-seriousAEs	40 1.8%	34 1.5%	26 1.2%	47 1.4%
AEs leading to study treatmentinterruption	268 11.8%	270 11.8%	228 10.5%	399 11.9%

9. Secondary Outcome

Title	Summary of Adverse Events (Extension Phase)
Description	Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs) occurring during the Extension phase of the study. AEs/SAEs are any signs or symptoms that occur during the study treatment.
Time Frame	From start of Extension phase, to end of treatment plus 30 days, up to approximately 2 years

Outcome Measure Data

Analysis Population Description
Extension Safety set: All patients who received at least one dose of study treatment during the Core Phase and who entered the Extension phase.

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	1267	1287	1279	1944
Patients with at least one AE	788 34.8%	845 37%	793 36.5%	1250 37.4%
AEs suspected to be related tostudy drug	40 1.8%	34 1.5%	43 2%	65 1.9%
Patients with at least one SAE	310 13.7%	326 14.3%	322 14.8%	465 13.9%
Discontinued due to SAEs	67 3%	71 3.1%	71 3.3%	98 2.9%
Discontinued due to non-seriousAEs	8 0.4%	6 0.3%	12 0.6%	8 0.2%
AEs leading to study treatmentinterruption	59 2.6%	72 3.2%	62 2.9%	100 3%

10. Secondary Outcome

Title	Substudy 1 (Core Phase): Change From Baseline of the Total Vessel Wall Area at Month 3 in the Bifurcation Region of the Index Carotid Artery
Description
Time Frame	3 months

Outcome Measure Data

Analysis Population Description
Data from subjects were not collected as the substudy was terminated prior to data collection.

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	0	0	0	0

11. Secondary Outcome

Title	Substudy 1 (Core Phase): Mean Total Vessel Wall Area Across the Left and Right Carotid Artery at Month 3 and Month 24
Description
Time Frame	24 months

Outcome Measure Data

Analysis Population Description
Data from subjects were not collected as the substudy was terminated prior to data collection.

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	0	0	0	0

12. Secondary Outcome

Title	Substudy 1 (Core Phase): Change From Baseline in Corresponding Total Vessel Wall Area in the Left and Right Carotid Arteries
Description
Time Frame	24 months

Outcome Measure Data

Analysis Population Description
Data from subjects were not collected as the substudy was terminated prior to data collection.

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	0	0	0	0

13. Secondary Outcome

Title	Substudy 1 (Core Phase): The Existence of a Baseline Total Vessel Wall Area by Treatment Interaction as Well as the Consistency of the Treatment Effect Across Subgroups
Description
Time Frame	24 months

Outcome Measure Data

Analysis Population Description
Data from subjects were not collected as the substudy was terminated prior to data collection.

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	0	0	0	0

14. Secondary Outcome

Title	Substudy 2 (Core Phase): Change From Baseline in Insulin Sensitivity Index
Description
Time Frame	From randomization up to approximately 6 years

Outcome Measure Data

Analysis Population Description
Data from subjects were not collected as the substudy was terminated prior to data collection.

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	0	0	0	0

15. Secondary Outcome

Title	Substudy 2 (Core Phase): Change From Baseline in OGTT Stimulated Area Under Curve (AUC) 0-120 Min of Glucose Concentration, Insulin Concentration, Pro-insulin Concentration, and Insulin Concentration/Glucose Concentration Ratio
Description
Time Frame	From randomization up to approximately 6 years

Outcome Measure Data

Analysis Population Description
Data from subjects were not collected as the substudy was terminated prior to data collection.

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	0	0	0	0

16. Secondary Outcome

Title	Substudy 2 (Core Phase): Change From Baseline in Fasting Pro-Insulin Concentration/Insulin Concentration Ratio
Description
Time Frame	From randomization up to approximately 6 years

Outcome Measure Data

Analysis Population Description
Data from subjects were not collected as the substudy was terminated prior to data collection.

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	0	0	0	0

17. Secondary Outcome

Title	Substudy 2 (Core Phase): Change From Baseline in OGTT Stimulated Area Under the Curve (AUC) 0-120 Min of C-peptide Concentration
Description
Time Frame	From randomization up to approximately 6 years

Outcome Measure Data

Analysis Population Description
Data from subjects were not collected as the substudy was terminated prior to data collection.

Arm/Group Title	Group I	Group II	Group III	Group IV
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy	Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy
Measure Participants	0	0	0	0

Adverse Events

	Group I		Group II		Group III		Group IV		Group V
Time Frame	Core phase: From randomization to end of treatment plus 30 days; up to approximately 6 years; Extension phase: From start of Extension phase, to end of treatment plus 30 days, up to approximately 2 years.
Adverse Event Reporting Description	AEs/SAEs are any signs or symptoms that occur during the study treatment. Groups I to IV show AE/SAEs during the Core phase; Group V shows AE/SAEs during the Extension phase. During the Core phase, CV events being study endpoints were exempt from AE/SAE reporting; in contrast, during the Extension phase, all CV events were reported as AEs/SAEs.

Arm/Group Title	Group I		Group II		Group III		Group IV		Group V
Arm/Group Description	Core phase: Blinded Canakinumab 300 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy		Core phase: Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy		Core phase: Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy		Core phase: Blinded matching placebo quarterly subcutaneous + standard of care (SoC) therapy Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy		Extension phase: Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care (SoC) therapy.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	239/2263 (10.6%)		240/2285 (10.5%)		228/2170 (10.5%)		378/3348 (11.3%)		211/5777 (3.7%)
Serious Adverse Events
	Group I		Group II		Group III		Group IV		Group V
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	759/2263 (33.5%)		743/2285 (32.5%)		686/2170 (31.6%)		1099/3348 (32.8%)		1216/5777 (21%)
Blood and lymphatic system disorders
Abnormal clotting factor	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Anaemia	15/2263 (0.7%)		10/2285 (0.4%)		4/2170 (0.2%)		14/3348 (0.4%)		10/5777 (0.2%)
Bone marrow oedema	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Coagulopathy	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Disseminated intravascular coagulation	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Febrile neutropenia	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Haemorrhagic anaemia	4/2263 (0.2%)		2/2285 (0.1%)		5/2170 (0.2%)		1/3348 (0%)		1/5777 (0%)
Heparin-induced thrombocytopenia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hilar lymphadenopathy	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Histiocytosis haematophagic	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hypochromic anaemia	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Immune thrombocytopenic purpura	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Iron deficiency anaemia	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		3/3348 (0.1%)		1/5777 (0%)
Leukocytosis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Leukopenia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Lymphadenitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Lymphadenopathy	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lymphadenopathy mediastinal	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Microcytic anaemia	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Monoclonal B-cell lymphocytosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Normochromic normocytic anaemia	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Normocytic anaemia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pancytopenia	1/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		3/3348 (0.1%)		1/5777 (0%)
Polycythaemia	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Splenic infarction	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Splenomegaly	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Thrombocytopenia	5/2263 (0.2%)		0/2285 (0%)		3/2170 (0.1%)		3/3348 (0.1%)		0/5777 (0%)
Thrombocytopenic purpura	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Cardiac disorders
Acute coronary syndrome	6/2263 (0.3%)		1/2285 (0%)		4/2170 (0.2%)		4/3348 (0.1%)		14/5777 (0.2%)
Acute left ventricular failure	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Acute myocardial infarction	2/2263 (0.1%)		2/2285 (0.1%)		2/2170 (0.1%)		7/3348 (0.2%)		71/5777 (1.2%)
Adams-Stokes syndrome	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Angina pectoris	42/2263 (1.9%)		41/2285 (1.8%)		37/2170 (1.7%)		76/3348 (2.3%)		66/5777 (1.1%)
Angina unstable	39/2263 (1.7%)		34/2285 (1.5%)		37/2170 (1.7%)		63/3348 (1.9%)		56/5777 (1%)
Aortic valve incompetence	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Aortic valve stenosis	3/2263 (0.1%)		2/2285 (0.1%)		2/2170 (0.1%)		3/3348 (0.1%)		2/5777 (0%)
Arrhythmia	4/2263 (0.2%)		0/2285 (0%)		1/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Arrhythmia supraventricular	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Arteriosclerosis coronary artery	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		2/5777 (0%)
Arteriospasm coronary	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Atrial fibrillation	3/2263 (0.1%)		6/2285 (0.3%)		4/2170 (0.2%)		4/3348 (0.1%)		49/5777 (0.8%)
Atrial flutter	2/2263 (0.1%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		6/5777 (0.1%)
Atrial tachycardia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Atrial thrombosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Atrioventricular block	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Atrioventricular block complete	1/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		4/3348 (0.1%)		4/5777 (0.1%)
Atrioventricular block first degree	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Atrioventricular block second degree	1/2263 (0%)		4/2285 (0.2%)		2/2170 (0.1%)		4/3348 (0.1%)		2/5777 (0%)
Bradyarrhythmia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Bradycardia	4/2263 (0.2%)		2/2285 (0.1%)		3/2170 (0.1%)		10/3348 (0.3%)		6/5777 (0.1%)
Cardiac aneurysm	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Cardiac arrest	2/2263 (0.1%)		7/2285 (0.3%)		7/2170 (0.3%)		15/3348 (0.4%)		9/5777 (0.2%)
Cardiac discomfort	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Cardiac failure	5/2263 (0.2%)		4/2285 (0.2%)		7/2170 (0.3%)		4/3348 (0.1%)		43/5777 (0.7%)
Cardiac failure acute	2/2263 (0.1%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		16/5777 (0.3%)
Cardiac failure chronic	5/2263 (0.2%)		2/2285 (0.1%)		2/2170 (0.1%)		2/3348 (0.1%)		15/5777 (0.3%)
Cardiac failure congestive	4/2263 (0.2%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		30/5777 (0.5%)
Cardiac fibrillation	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Cardiac pseudoaneurysm	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Cardiac tamponade	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Cardiac ventricular thrombosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Cardio-respiratory arrest	2/2263 (0.1%)		2/2285 (0.1%)		3/2170 (0.1%)		1/3348 (0%)		6/5777 (0.1%)
Cardiogenic shock	1/2263 (0%)		3/2285 (0.1%)		3/2170 (0.1%)		7/3348 (0.2%)		9/5777 (0.2%)
Cardiomegaly	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Cardiomyopathy	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Cardiopulmonary failure	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Conduction disorder	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Congestive cardiomyopathy	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Cor pulmonale	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Coronary artery disease	9/2263 (0.4%)		10/2285 (0.4%)		5/2170 (0.2%)		20/3348 (0.6%)		27/5777 (0.5%)
Coronary artery insufficiency	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Coronary artery occlusion	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		3/5777 (0.1%)
Coronary artery stenosis	2/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		14/5777 (0.2%)
Hypertensive heart disease	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Intracardiac thrombus	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Ischaemic cardiomyopathy	3/2263 (0.1%)		5/2285 (0.2%)		2/2170 (0.1%)		4/3348 (0.1%)		6/5777 (0.1%)
Left ventricular dysfunction	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		3/5777 (0.1%)
Left ventricular failure	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Left ventricular hypertrophy	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Microvascular coronary artery disease	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Mitral valve incompetence	5/2263 (0.2%)		3/2285 (0.1%)		0/2170 (0%)		1/3348 (0%)		3/5777 (0.1%)
Myocardial infarction	4/2263 (0.2%)		2/2285 (0.1%)		5/2170 (0.2%)		2/3348 (0.1%)		42/5777 (0.7%)
Myocardial ischaemia	6/2263 (0.3%)		3/2285 (0.1%)		5/2170 (0.2%)		6/3348 (0.2%)		10/5777 (0.2%)
Nodal arrhythmia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Palpitations	3/2263 (0.1%)		2/2285 (0.1%)		2/2170 (0.1%)		1/3348 (0%)		1/5777 (0%)
Pericardial effusion	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pericarditis	2/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Prinzmetal angina	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Pulseless electrical activity	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Right ventricular dysfunction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Right ventricular failure	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Silent myocardial infarction	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Sinus arrest	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Sinus bradycardia	3/2263 (0.1%)		0/2285 (0%)		2/2170 (0.1%)		2/3348 (0.1%)		1/5777 (0%)
Sinus node dysfunction	4/2263 (0.2%)		2/2285 (0.1%)		5/2170 (0.2%)		4/3348 (0.1%)		6/5777 (0.1%)
Sinus tachycardia	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Stress cardiomyopathy	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Supraventricular tachycardia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Tachyarrhythmia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Tachycardia	3/2263 (0.1%)		1/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Torsade de pointes	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Tricuspid valve incompetence	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Trifascicular block	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Ventricular arrhythmia	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Ventricular extrasystoles	1/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		2/3348 (0.1%)		1/5777 (0%)
Ventricular fibrillation	4/2263 (0.2%)		9/2285 (0.4%)		3/2170 (0.1%)		7/3348 (0.2%)		7/5777 (0.1%)
Ventricular tachyarrhythmia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Ventricular tachycardia	10/2263 (0.4%)		5/2285 (0.2%)		9/2170 (0.4%)		16/3348 (0.5%)		18/5777 (0.3%)
Congenital, familial and genetic disorders
Atrial septal defect	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Branchial cyst	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Cerebrovascular arteriovenous malformation	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Haemorrhagic arteriovenous malformation	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hereditary haemochromatosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hydrocele	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Nonketotic hyperglycinaemia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Phimosis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pyloric stenosis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Tracheo-oesophageal fistula	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Ear and labyrinth disorders
Cerumen impaction	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Ear pain	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hypoacusis	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Meniere's disease	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Otosclerosis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Presbyacusis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Sudden hearing loss	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Tympanic membrane perforation	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Vertigo	3/2263 (0.1%)		5/2285 (0.2%)		4/2170 (0.2%)		4/3348 (0.1%)		4/5777 (0.1%)
Vertigo positional	2/2263 (0.1%)		2/2285 (0.1%)		3/2170 (0.1%)		2/3348 (0.1%)		2/5777 (0%)
Endocrine disorders
Goitre	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Hyperparathyroidism primary	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Hyperthyroidism	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hypopituitarism	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hypothyroidism	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Inappropriate antidiuretic hormone secretion	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Primary hyperaldosteronism	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Toxic goitre	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Eye disorders
Amaurosis fugax	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Angle closure glaucoma	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Blindness	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Blindness transient	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Blindness unilateral	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Cataract	4/2263 (0.2%)		8/2285 (0.4%)		5/2170 (0.2%)		12/3348 (0.4%)		8/5777 (0.1%)
Cataract cortical	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Cataract diabetic	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Cataract nuclear	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Corneal degeneration	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Corneal infiltrates	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Dacryostenosis acquired	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Diabetic retinopathy	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Eye haemorrhage	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Eyelid ptosis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Glaucoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Iridocyclitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Lens dislocation	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Macular degeneration	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Macular fibrosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Macular hole	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Macular oedema	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Neovascular age-related macular degeneration	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Ocular ischaemic syndrome	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Papilloedema	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Retinal artery thrombosis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Retinal detachment	2/2263 (0.1%)		2/2285 (0.1%)		0/2170 (0%)		2/3348 (0.1%)		2/5777 (0%)
Retinal haemorrhage	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Retinal vein occlusion	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Retinal vein thrombosis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Vitreous haemorrhage	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Gastrointestinal disorders
Abdominal adhesions	0/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		1/3348 (0%)		1/5777 (0%)
Abdominal discomfort	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Abdominal distension	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Abdominal hernia	3/2263 (0.1%)		1/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Abdominal pain	7/2263 (0.3%)		4/2285 (0.2%)		10/2170 (0.5%)		10/3348 (0.3%)		6/5777 (0.1%)
Abdominal pain lower	0/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Abdominal pain upper	6/2263 (0.3%)		2/2285 (0.1%)		3/2170 (0.1%)		2/3348 (0.1%)		4/5777 (0.1%)
Acute abdomen	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Alcoholic pancreatitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Anal fissure	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Anal haemorrhage	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Anal skin tags	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Anal ulcer	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Anal ulcer haemorrhage	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Anorectal disorder	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Appendiceal mucocoele	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Appendix disorder	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Ascites	0/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Change of bowel habit	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Chronic gastritis	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Colitis	3/2263 (0.1%)		3/2285 (0.1%)		2/2170 (0.1%)		3/3348 (0.1%)		4/5777 (0.1%)
Colitis ischaemic	1/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		1/3348 (0%)		1/5777 (0%)
Colitis microscopic	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Colitis ulcerative	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Colonic fistula	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Constipation	4/2263 (0.2%)		2/2285 (0.1%)		1/2170 (0%)		4/3348 (0.1%)		3/5777 (0.1%)
Crohn's disease	1/2263 (0%)		3/2285 (0.1%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Dental caries	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Diabetic gastroenteropathy	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Diarrhoea	3/2263 (0.1%)		5/2285 (0.2%)		4/2170 (0.2%)		2/3348 (0.1%)		3/5777 (0.1%)
Dieulafoy's vascular malformation	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Diverticulum	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Diverticulum intestinal	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Diverticulum intestinal haemorrhagic	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Duodenal stenosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Duodenal ulcer	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Duodenal ulcer haemorrhage	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Duodenal ulcer perforation	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Duodenitis	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Dyspepsia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Dysphagia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		2/5777 (0%)
Enteritis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Enterocolitis	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Enterovesical fistula	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Epigastric discomfort	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Erosive duodenitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Erosive oesophagitis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Faecaloma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Faeces discoloured	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Flatulence	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Food poisoning	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Gallstone ileus	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gastric haemorrhage	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Gastric ulcer	7/2263 (0.3%)		6/2285 (0.3%)		0/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Gastric ulcer haemorrhage	2/2263 (0.1%)		1/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Gastric ulcer perforation	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gastric volvulus	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Gastritis	4/2263 (0.2%)		1/2285 (0%)		4/2170 (0.2%)		6/3348 (0.2%)		4/5777 (0.1%)
Gastritis erosive	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Gastritis haemorrhagic	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gastroduodenitis	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gastrointestinal angiodysplasia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gastrointestinal disorder	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Gastrointestinal erosion	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Gastrointestinal haemorrhage	13/2263 (0.6%)		16/2285 (0.7%)		14/2170 (0.6%)		13/3348 (0.4%)		5/5777 (0.1%)
Gastrointestinal necrosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Gastrointestinal pain	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gastrointestinal perforation	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Gastrointestinal ulcer	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gastrointestinal vascular malformation	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Gastrooesophageal reflux disease	1/2263 (0%)		5/2285 (0.2%)		1/2170 (0%)		4/3348 (0.1%)		4/5777 (0.1%)
Haematemesis	1/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		2/3348 (0.1%)		3/5777 (0.1%)
Haematochezia	1/2263 (0%)		3/2285 (0.1%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Haemorrhagic necrotic pancreatitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Haemorrhoidal haemorrhage	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Haemorrhoids	2/2263 (0.1%)		3/2285 (0.1%)		1/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Haemorrhoids thrombosed	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hiatus hernia	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Ileal ulcer	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Ileus	3/2263 (0.1%)		1/2285 (0%)		2/2170 (0.1%)		3/3348 (0.1%)		2/5777 (0%)
Ileus paralytic	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Impaired gastric emptying	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Incarcerated inguinal hernia	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Incarcerated umbilical hernia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Inflammatory bowel disease	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Inguinal hernia	8/2263 (0.4%)		5/2285 (0.2%)		7/2170 (0.3%)		7/3348 (0.2%)		8/5777 (0.1%)
Inguinal hernia strangulated	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Intestinal fistula	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Intestinal haemorrhage	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Intestinal infarction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Intestinal ischaemia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Intestinal mass	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Intestinal obstruction	2/2263 (0.1%)		1/2285 (0%)		3/2170 (0.1%)		2/3348 (0.1%)		2/5777 (0%)
Intestinal perforation	2/2263 (0.1%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Intestinal ulcer	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Irritable bowel syndrome	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Ischaemic enteritis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Large intestinal obstruction	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Large intestinal stenosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Large intestine perforation	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Large intestine polyp	3/2263 (0.1%)		4/2285 (0.2%)		2/2170 (0.1%)		12/3348 (0.4%)		6/5777 (0.1%)
Lower gastrointestinal haemorrhage	1/2263 (0%)		4/2285 (0.2%)		1/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Mallory-Weiss syndrome	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Melaena	2/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		3/5777 (0.1%)
Mesenteric artery stenosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Mesenteric artery thrombosis	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Mesenteric vascular insufficiency	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Mouth cyst	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Mouth ulceration	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Narcotic bowel syndrome	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Nausea	4/2263 (0.2%)		3/2285 (0.1%)		2/2170 (0.1%)		4/3348 (0.1%)		0/5777 (0%)
Obstruction gastric	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Odynophagia	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Oesophageal obstruction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Oesophageal perforation	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Oesophageal rupture	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Oesophageal stenosis	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Oesophageal ulcer	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Oesophageal varices haemorrhage	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Oesophagitis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Pancreatic cyst	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pancreatic disorder	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pancreatic duct dilatation	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pancreatic mass	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pancreatic pseudocyst	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pancreatitis	6/2263 (0.3%)		6/2285 (0.3%)		3/2170 (0.1%)		11/3348 (0.3%)		3/5777 (0.1%)
Pancreatitis acute	3/2263 (0.1%)		6/2285 (0.3%)		2/2170 (0.1%)		3/3348 (0.1%)		6/5777 (0.1%)
Pancreatitis chronic	0/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Pancreatitis necrotising	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Peptic ulcer	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Peptic ulcer haemorrhage	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Peritoneal haemorrhage	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pneumatosis intestinalis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pneumoperitoneum	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Proctalgia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Proctitis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Ranula	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Rectal haemorrhage	1/2263 (0%)		6/2285 (0.3%)		1/2170 (0%)		1/3348 (0%)		3/5777 (0.1%)
Rectal lesion	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Rectal perforation	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Rectal polyp	1/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Retroperitoneal haematoma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Retroperitoneal haemorrhage	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Salivary gland calculus	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Small intestinal haemorrhage	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Small intestinal obstruction	2/2263 (0.1%)		1/2285 (0%)		2/2170 (0.1%)		1/3348 (0%)		9/5777 (0.2%)
Small intestinal perforation	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Small intestine ulcer	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Subileus	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Thrombosis mesenteric vessel	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Umbilical hernia	1/2263 (0%)		4/2285 (0.2%)		2/2170 (0.1%)		4/3348 (0.1%)		0/5777 (0%)
Upper gastrointestinal haemorrhage	3/2263 (0.1%)		8/2285 (0.4%)		8/2170 (0.4%)		8/3348 (0.2%)		3/5777 (0.1%)
Vomiting	5/2263 (0.2%)		4/2285 (0.2%)		2/2170 (0.1%)		4/3348 (0.1%)		0/5777 (0%)
General disorders
Adverse drug reaction	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Asthenia	4/2263 (0.2%)		2/2285 (0.1%)		1/2170 (0%)		3/3348 (0.1%)		3/5777 (0.1%)
Cardiac death	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		4/5777 (0.1%)
Chest discomfort	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Chest pain	3/2263 (0.1%)		12/2285 (0.5%)		2/2170 (0.1%)		9/3348 (0.3%)		9/5777 (0.2%)
Chills	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Complication associated with device	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Death	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		4/3348 (0.1%)		12/5777 (0.2%)
Drowning	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Drug intolerance	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Exercise tolerance decreased	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Facial pain	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Fatigue	2/2263 (0.1%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gait disturbance	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
General physical health deterioration	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		2/5777 (0%)
Generalised oedema	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Hernia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Heteroplasia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Hyperplasia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Hypothermia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Impaired healing	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Implant site irritation	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Incarcerated hernia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Inflammation	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Influenza like illness	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Injection site reaction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Ischaemic ulcer	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Local swelling	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Malaise	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Mass	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Multiple organ dysfunction syndrome	3/2263 (0.1%)		2/2285 (0.1%)		0/2170 (0%)		3/3348 (0.1%)		6/5777 (0.1%)
Necrosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Non-cardiac chest pain	44/2263 (1.9%)		48/2285 (2.1%)		39/2170 (1.8%)		75/3348 (2.2%)		35/5777 (0.6%)
Oedema peripheral	2/2263 (0.1%)		0/2285 (0%)		1/2170 (0%)		3/3348 (0.1%)		1/5777 (0%)
Pacemaker syndrome	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pain	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Polyp	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pseudocyst	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pyrexia	4/2263 (0.2%)		4/2285 (0.2%)		6/2170 (0.3%)		5/3348 (0.1%)		3/5777 (0.1%)
Stent-graft endoleak	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Sudden cardiac death	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		11/5777 (0.2%)
Sudden death	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		7/5777 (0.1%)
Surgical failure	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Systemic inflammatory response syndrome	1/2263 (0%)		0/2285 (0%)		3/2170 (0.1%)		2/3348 (0.1%)		0/5777 (0%)
Vascular stent restenosis	2/2263 (0.1%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Vascular stent stenosis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		3/5777 (0.1%)
Vascular stent thrombosis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Vessel puncture site haemorrhage	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hepatobiliary disorders
Acute hepatic failure	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Alcoholic liver disease	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Autoimmune hepatitis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bile duct stenosis	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bile duct stone	4/2263 (0.2%)		0/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Biliary cirrhosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Biliary colic	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Biliary dilatation	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Biliary fistula	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Cholangitis	2/2263 (0.1%)		2/2285 (0.1%)		4/2170 (0.2%)		0/3348 (0%)		0/5777 (0%)
Cholangitis acute	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Cholecystitis	11/2263 (0.5%)		4/2285 (0.2%)		8/2170 (0.4%)		9/3348 (0.3%)		7/5777 (0.1%)
Cholecystitis acute	5/2263 (0.2%)		7/2285 (0.3%)		4/2170 (0.2%)		7/3348 (0.2%)		5/5777 (0.1%)
Cholelithiasis	8/2263 (0.4%)		8/2285 (0.4%)		8/2170 (0.4%)		18/3348 (0.5%)		4/5777 (0.1%)
Cholestasis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Drug-induced liver injury	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gallbladder polyp	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Haemorrhagic hepatic cyst	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hepatic cirrhosis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		4/5777 (0.1%)
Hepatic congestion	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hepatic failure	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hepatic function abnormal	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hepatic steatosis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hepatic vein thrombosis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hepatitis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hepatitis toxic	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hepatomegaly	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hepatorenal failure	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hepatosplenomegaly	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hydrocholecystis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Ischaemic hepatitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Jaundice cholestatic	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Liver disorder	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Liver injury	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Non-alcoholic fatty liver	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Non-alcoholic steatohepatitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Portal vein thrombosis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Steatohepatitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Immune system disorders
Allergy to arthropod sting	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Anaphylactic reaction	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Anaphylactic shock	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Contrast media allergy	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Drug hypersensitivity	0/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Hypersensitivity	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Infections and infestations
Abdominal abscess	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Abdominal infection	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Abdominal sepsis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Abscess intestinal	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Abscess jaw	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Abscess limb	4/2263 (0.2%)		1/2285 (0%)		3/2170 (0.1%)		3/3348 (0.1%)		0/5777 (0%)
Abscess neck	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Abscess oral	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Abscess soft tissue	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Acute hepatitis B	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Acute sinusitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Anal abscess	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		2/5777 (0%)
Appendicitis	3/2263 (0.1%)		4/2285 (0.2%)		6/2170 (0.3%)		4/3348 (0.1%)		3/5777 (0.1%)
Appendicitis perforated	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Arthritis bacterial	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Arthritis infective	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		1/5777 (0%)
Atypical pneumonia	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Bacteraemia	3/2263 (0.1%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Bacterial disease carrier	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bacterial pyelonephritis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Bacterial sepsis	1/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bacteroides infection	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Bartholin's abscess	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Beta haemolytic streptococcal infection	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bone abscess	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bronchitis	10/2263 (0.4%)		9/2285 (0.4%)		6/2170 (0.3%)		14/3348 (0.4%)		10/5777 (0.2%)
Bronchitis bacterial	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Bursitis infective	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Bursitis infective staphylococcal	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Campylobacter gastroenteritis	2/2263 (0.1%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Campylobacter infection	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Candida infection	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Carbuncle	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Cellulitis	29/2263 (1.3%)		32/2285 (1.4%)		19/2170 (0.9%)		27/3348 (0.8%)		22/5777 (0.4%)
Cellulitis gangrenous	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Cellulitis of male external genital organ	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Cellulitis staphylococcal	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Central nervous system infection	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Chikungunya virus infection	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Cholangitis infective	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Cholecystitis infective	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Chorioretinitis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Chronic sinusitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Chronic tonsillitis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Clostridial infection	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Clostridium difficile colitis	3/2263 (0.1%)		1/2285 (0%)		4/2170 (0.2%)		1/3348 (0%)		1/5777 (0%)
Clostridium difficile infection	2/2263 (0.1%)		1/2285 (0%)		2/2170 (0.1%)		1/3348 (0%)		0/5777 (0%)
Colonic abscess	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Conjunctivitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Corona virus infection	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Creutzfeldt-Jakob disease	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Cystitis	2/2263 (0.1%)		0/2285 (0%)		3/2170 (0.1%)		1/3348 (0%)		1/5777 (0%)
Dengue fever	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Device related infection	0/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		4/3348 (0.1%)		1/5777 (0%)
Device related sepsis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Diabetic foot infection	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Diabetic gangrene	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Diarrhoea infectious	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Diverticulitis	8/2263 (0.4%)		9/2285 (0.4%)		8/2170 (0.4%)		13/3348 (0.4%)		6/5777 (0.1%)
Ear infection	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Empyema	2/2263 (0.1%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Endocarditis	1/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		2/3348 (0.1%)		1/5777 (0%)
Endocarditis bacterial	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Enteritis infectious	0/2263 (0%)		0/2285 (0%)		3/2170 (0.1%)		2/3348 (0.1%)		0/5777 (0%)
Epididymitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Epiglottitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Erysipelas	6/2263 (0.3%)		12/2285 (0.5%)		6/2170 (0.3%)		9/3348 (0.3%)		13/5777 (0.2%)
Escherichia sepsis	0/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		3/3348 (0.1%)		0/5777 (0%)
Escherichia urinary tract infection	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
External ear cellulitis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Folliculitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Fungal skin infection	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Furuncle	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Gallbladder abscess	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Gallbladder empyema	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Gangrene	1/2263 (0%)		1/2285 (0%)		5/2170 (0.2%)		0/3348 (0%)		2/5777 (0%)
Gastritis viral	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Gastroenteritis	6/2263 (0.3%)		5/2285 (0.2%)		6/2170 (0.3%)		8/3348 (0.2%)		4/5777 (0.1%)
Gastroenteritis clostridial	2/2263 (0.1%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Gastroenteritis rotavirus	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Gastroenteritis salmonella	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Gastroenteritis viral	2/2263 (0.1%)		0/2285 (0%)		2/2170 (0.1%)		1/3348 (0%)		0/5777 (0%)
Gastrointestinal bacterial infection	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gastrointestinal infection	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gastrointestinal viral infection	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Groin infection	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Haematoma infection	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Haemophilus infection	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Haemophilus sepsis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Haemorrhagic pneumonia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Helicobacter infection	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hepatic amoebiasis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hepatitis viral	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Herpes ophthalmic	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Herpes zoster	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		4/3348 (0.1%)		1/5777 (0%)
Human ehrlichiosis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hypopyon	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Implant site abscess	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Implant site infection	0/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		1/5777 (0%)
Incision site cellulitis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Incision site infection	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Infected bite	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Infected cyst	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Infected skin ulcer	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Infection	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Infectious colitis	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Infectious pleural effusion	3/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Infective exacerbation of chronic obstructive airways disease	5/2263 (0.2%)		0/2285 (0%)		2/2170 (0.1%)		3/3348 (0.1%)		1/5777 (0%)
Infective spondylitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Influenza	4/2263 (0.2%)		6/2285 (0.3%)		2/2170 (0.1%)		3/3348 (0.1%)		9/5777 (0.2%)
Intervertebral discitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Joint abscess	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Labyrinthitis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Leptospirosis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Liver abscess	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Localised infection	2/2263 (0.1%)		2/2285 (0.1%)		3/2170 (0.1%)		5/3348 (0.1%)		4/5777 (0.1%)
Lower respiratory tract infection	3/2263 (0.1%)		2/2285 (0.1%)		4/2170 (0.2%)		4/3348 (0.1%)		4/5777 (0.1%)
Lung abscess	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lung infection	2/2263 (0.1%)		0/2285 (0%)		3/2170 (0.1%)		1/3348 (0%)		1/5777 (0%)
Lyme disease	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lymphangitis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Malaria	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Mastoiditis	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Mediastinitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Medical device site infection	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Meningitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Meningitis bacterial	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Meningococcal sepsis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Mesenteric abscess	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Metapneumovirus infection	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Muscle abscess	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Mycobacterial infection	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Mycobacterium avium complex infection	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Necrotising fasciitis	0/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Neutropenic sepsis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Oesophageal candidiasis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Orchitis	1/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Osteomyelitis	4/2263 (0.2%)		3/2285 (0.1%)		3/2170 (0.1%)		4/3348 (0.1%)		10/5777 (0.2%)
Osteomyelitis bacterial	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Osteomyelitis blastomyces	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Otitis externa	0/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Otitis media	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Otitis media acute	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Otitis media chronic	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pancreatic abscess	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Parainfluenzae virus infection	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Parametritis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Paronychia	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Parotitis	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pelvic abscess	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Perichondritis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Perineal abscess	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Periodontitis	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Periorbital cellulitis	0/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		1/5777 (0%)
Perirectal abscess	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Peritoneal abscess	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Peritonitis	2/2263 (0.1%)		1/2285 (0%)		3/2170 (0.1%)		2/3348 (0.1%)		2/5777 (0%)
Pharyngeal abscess	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pharyngitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pharyngitis streptococcal	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pilonidal cyst	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Pneumococcal sepsis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pneumonia	67/2263 (3%)		60/2285 (2.6%)		53/2170 (2.4%)		83/3348 (2.5%)		70/5777 (1.2%)
Pneumonia bacterial	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		1/5777 (0%)
Pneumonia escherichia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pneumonia haemophilus	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pneumonia klebsiella	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pneumonia legionella	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pneumonia necrotising	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pneumonia pneumococcal	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Pneumonia pseudomonal	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pneumonia staphylococcal	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Post procedural cellulitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Post procedural infection	1/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		4/5777 (0.1%)
Post procedural sepsis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Postoperative abscess	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Postoperative wound infection	2/2263 (0.1%)		2/2285 (0.1%)		2/2170 (0.1%)		1/3348 (0%)		4/5777 (0.1%)
Proctitis infectious	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Propionibacterium infection	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pseudomembranous colitis	1/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Pseudomonal bacteraemia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pseudomonas bronchitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pseudomonas infection	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Psoas abscess	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pulmonary sepsis	1/2263 (0%)		2/2285 (0.1%)		2/2170 (0.1%)		1/3348 (0%)		2/5777 (0%)
Pulmonary tuberculosis	1/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pyelitis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pyelonephritis	3/2263 (0.1%)		1/2285 (0%)		2/2170 (0.1%)		5/3348 (0.1%)		2/5777 (0%)
Pyelonephritis acute	1/2263 (0%)		5/2285 (0.2%)		1/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Pyoderma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pyuria	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Renal abscess	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		3/5777 (0.1%)
Respiratory tract infection	2/2263 (0.1%)		7/2285 (0.3%)		0/2170 (0%)		7/3348 (0.2%)		2/5777 (0%)
Respiratory tract infection viral	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Rhinitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Rubella	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Salmonellosis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Scrotal abscess	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Scrub typhus	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Sepsis	19/2263 (0.8%)		25/2285 (1.1%)		15/2170 (0.7%)		19/3348 (0.6%)		22/5777 (0.4%)
Sepsis syndrome	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Septic embolus	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Septic necrosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Septic shock	6/2263 (0.3%)		8/2285 (0.4%)		6/2170 (0.3%)		11/3348 (0.3%)		3/5777 (0.1%)
Sialoadenitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Sinusitis	3/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		3/5777 (0.1%)
Sinusitis fungal	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Staphylococcal abscess	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Staphylococcal bacteraemia	2/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		3/5777 (0.1%)
Staphylococcal infection	1/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		1/3348 (0%)		2/5777 (0%)
Staphylococcal mediastinitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Staphylococcal sepsis	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Streptococcal bacteraemia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Streptococcal sepsis	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Subcutaneous abscess	4/2263 (0.2%)		3/2285 (0.1%)		2/2170 (0.1%)		3/3348 (0.1%)		0/5777 (0%)
Subdiaphragmatic abscess	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Subdural empyema	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Testicular abscess	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Tetanus	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Tonsillitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Tooth abscess	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Tracheobronchitis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Tuberculosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Upper respiratory tract infection	0/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Urinary tract infection	13/2263 (0.6%)		11/2285 (0.5%)		10/2170 (0.5%)		21/3348 (0.6%)		19/5777 (0.3%)
Urinary tract infection bacterial	3/2263 (0.1%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Urinary tract infection enterococcal	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Urinary tract infection fungal	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Urinary tract infection pseudomonal	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Urosepsis	4/2263 (0.2%)		4/2285 (0.2%)		5/2170 (0.2%)		3/3348 (0.1%)		7/5777 (0.1%)
Vestibular neuronitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Viral cardiomyopathy	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Viral diarrhoea	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Viral infection	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Viral upper respiratory tract infection	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Vulval abscess	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Wound infection	0/2263 (0%)		3/2285 (0.1%)		4/2170 (0.2%)		0/3348 (0%)		2/5777 (0%)
Wound infection bacterial	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Wound infection staphylococcal	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Wound sepsis	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Injury, poisoning and procedural complications
Abdominal injury	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Accident	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Accidental overdose	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Acetabulum fracture	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Alcohol poisoning	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Anaemia postoperative	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Anastomotic leak	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Animal bite	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Ankle fracture	5/2263 (0.2%)		0/2285 (0%)		3/2170 (0.1%)		4/3348 (0.1%)		4/5777 (0.1%)
Arterial injury	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Arthropod sting	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Asbestosis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bone contusion	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Brain contusion	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Cardiac function disturbance postoperative	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Central cord syndrome	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Cervical vertebral fracture	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		2/5777 (0%)
Chest injury	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Clavicle fracture	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		2/5777 (0%)
Closed globe injury	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Comminuted fracture	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Concussion	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Contusion	2/2263 (0.1%)		1/2285 (0%)		3/2170 (0.1%)		5/3348 (0.1%)		0/5777 (0%)
Coronary artery restenosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Craniocerebral injury	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Dural tear	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Epicondylitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Face injury	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Facial bones fracture	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Fall	3/2263 (0.1%)		1/2285 (0%)		2/2170 (0.1%)		3/3348 (0.1%)		9/5777 (0.2%)
Femoral neck fracture	3/2263 (0.1%)		5/2285 (0.2%)		2/2170 (0.1%)		5/3348 (0.1%)		2/5777 (0%)
Femur fracture	1/2263 (0%)		3/2285 (0.1%)		2/2170 (0.1%)		5/3348 (0.1%)		4/5777 (0.1%)
Foot fracture	2/2263 (0.1%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Forearm fracture	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Foreign body	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Fracture displacement	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gallbladder injury	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gastrointestinal stoma complication	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gastrointestinal stoma necrosis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gun shot wound	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hand fracture	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Head injury	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		3/3348 (0.1%)		2/5777 (0%)
Hip fracture	1/2263 (0%)		2/2285 (0.1%)		3/2170 (0.1%)		6/3348 (0.2%)		2/5777 (0%)
Humerus fracture	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		4/3348 (0.1%)		2/5777 (0%)
Incision site haemorrhage	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Incision site pain	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Incisional hernia	0/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		3/3348 (0.1%)		2/5777 (0%)
Incisional hernia, obstructive	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Injury	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Intentional overdose	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Intentional product misuse	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Jaw fracture	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Joint dislocation	4/2263 (0.2%)		0/2285 (0%)		3/2170 (0.1%)		3/3348 (0.1%)		0/5777 (0%)
Joint injury	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Laceration	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Ligament injury	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Ligament rupture	0/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		1/5777 (0%)
Ligament sprain	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Limb injury	1/2263 (0%)		2/2285 (0.1%)		2/2170 (0.1%)		0/3348 (0%)		1/5777 (0%)
Limb traumatic amputation	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Lower limb fracture	1/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		3/3348 (0.1%)		1/5777 (0%)
Lumbar vertebral fracture	2/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		2/5777 (0%)
Meniscus injury	0/2263 (0%)		3/2285 (0.1%)		5/2170 (0.2%)		8/3348 (0.2%)		0/5777 (0%)
Multiple fractures	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Multiple injuries	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Muscle contusion	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Muscle rupture	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Muscle strain	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Musculoskeletal foreign body	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Nerve injury	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Overdose	2/2263 (0.1%)		1/2285 (0%)		2/2170 (0.1%)		2/3348 (0.1%)		0/5777 (0%)
Patella fracture	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pelvic fracture	1/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		1/3348 (0%)		0/5777 (0%)
Peripheral artery restenosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Periprosthetic fracture	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Perirenal haematoma	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pneumoconiosis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pneumothorax traumatic	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Post procedural complication	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Post procedural discharge	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Post procedural fever	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Post procedural haematoma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Post procedural haemorrhage	3/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Postoperative hernia	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Postoperative wound complication	1/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Procedural complication	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Procedural intestinal perforation	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Procedural pain	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pubis fracture	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Radiation mucositis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Radius fracture	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		3/3348 (0.1%)		1/5777 (0%)
Rib fracture	4/2263 (0.2%)		3/2285 (0.1%)		3/2170 (0.1%)		7/3348 (0.2%)		0/5777 (0%)
Road traffic accident	4/2263 (0.2%)		1/2285 (0%)		2/2170 (0.1%)		3/3348 (0.1%)		3/5777 (0.1%)
Scapula fracture	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Scratch	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Seroma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Skeletal injury	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Skin laceration	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Skull fracture	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Spinal column injury	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Spinal compression fracture	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		5/3348 (0.1%)		1/5777 (0%)
Spinal cord injury	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Spinal cord injury cervical	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Spinal fracture	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Splenic rupture	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Stab wound	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Sternal fracture	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Stress fracture	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Subarachnoid haemorrhage	2/2263 (0.1%)		2/2285 (0.1%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Subdural haematoma	2/2263 (0.1%)		4/2285 (0.2%)		4/2170 (0.2%)		5/3348 (0.1%)		5/5777 (0.1%)
Subdural haemorrhage	2/2263 (0.1%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Tendon injury	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Tendon rupture	4/2263 (0.2%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Thermal burn	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Thoracic vertebral fracture	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Tibia fracture	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		2/5777 (0%)
Tooth fracture	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Toxicity to various agents	2/2263 (0.1%)		0/2285 (0%)		2/2170 (0.1%)		2/3348 (0.1%)		0/5777 (0%)
Tracheal haemorrhage	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Traumatic amputation	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Traumatic arthritis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Traumatic haematoma	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Traumatic haemothorax	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Traumatic intracranial haemorrhage	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Ulna fracture	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Upper limb fracture	1/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		3/3348 (0.1%)		2/5777 (0%)
Urinary retention postoperative	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Vascular graft complication	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Vascular pseudoaneurysm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Vascular pseudoaneurysm ruptured	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Wound dehiscence	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Wound secretion	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Wrist fracture	0/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Investigations
Alanine aminotransferase increased	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Anticoagulation drug level above therapeutic	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Aspartate aminotransferase increased	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Blood creatine phosphokinase MB increased	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Blood creatine phosphokinase increased	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Blood creatinine increased	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Blood glucose increased	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Blood magnesium decreased	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Blood pressure increased	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Blood urine present	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Body mass index decreased	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Central venous pressure increased	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Chest X-ray abnormal	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Clostridium test positive	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Ejection fraction decreased	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Haemoglobin decreased	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hepatic enzyme increased	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Human metapneumovirus test positive	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Imaging procedure abnormal	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
International normalised ratio decreased	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
International normalised ratio increased	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Liver function test abnormal	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Liver function test increased	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
N-terminal prohormone brain natriuretic peptide increased	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Oxygen saturation decreased	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Platelet count decreased	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Quality of life decreased	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Scan myocardial perfusion abnormal	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Troponin T increased	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Troponin increased	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Volume blood decreased	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Weight decreased	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Weight increased	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
White blood cell count increased	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Metabolism and nutrition disorders
Acidosis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Cachexia	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Dehydration	5/2263 (0.2%)		6/2285 (0.3%)		6/2170 (0.3%)		6/3348 (0.2%)		8/5777 (0.1%)
Diabetes mellitus	3/2263 (0.1%)		10/2285 (0.4%)		1/2170 (0%)		11/3348 (0.3%)		8/5777 (0.1%)
Diabetes mellitus inadequate control	2/2263 (0.1%)		1/2285 (0%)		7/2170 (0.3%)		3/3348 (0.1%)		1/5777 (0%)
Diabetes with hyperosmolarity	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Diabetic complication	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Diabetic ketoacidosis	1/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Diabetic metabolic decompensation	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Electrolyte imbalance	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Fluid overload	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Gout	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Hyperammonaemia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hypercalcaemia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hyperchloraemia	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hyperglycaemia	3/2263 (0.1%)		4/2285 (0.2%)		3/2170 (0.1%)		6/3348 (0.2%)		4/5777 (0.1%)
Hyperglycaemic hyperosmolar nonketotic syndrome	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Hyperkalaemia	3/2263 (0.1%)		4/2285 (0.2%)		3/2170 (0.1%)		3/3348 (0.1%)		7/5777 (0.1%)
Hypermagnesaemia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hyperuricaemia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Hypoalbuminaemia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hypocalcaemia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Hypoglycaemia	4/2263 (0.2%)		4/2285 (0.2%)		3/2170 (0.1%)		9/3348 (0.3%)		4/5777 (0.1%)
Hypokalaemia	1/2263 (0%)		1/2285 (0%)		3/2170 (0.1%)		9/3348 (0.3%)		4/5777 (0.1%)
Hypomagnesaemia	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hyponatraemia	0/2263 (0%)		2/2285 (0.1%)		4/2170 (0.2%)		2/3348 (0.1%)		4/5777 (0.1%)
Hypovolaemia	1/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		1/3348 (0%)		0/5777 (0%)
Insulin resistant diabetes	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Insulin-requiring type 2 diabetes mellitus	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Ketoacidosis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lactic acidosis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Malnutrition	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Metabolic acidosis	1/2263 (0%)		2/2285 (0.1%)		2/2170 (0.1%)		1/3348 (0%)		0/5777 (0%)
Obesity	5/2263 (0.2%)		1/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		4/5777 (0.1%)
Type 1 diabetes mellitus	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Type 2 diabetes mellitus	3/2263 (0.1%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		4/5777 (0.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/2263 (0.1%)		5/2285 (0.2%)		2/2170 (0.1%)		4/3348 (0.1%)		6/5777 (0.1%)
Arthritis	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		2/5777 (0%)
Arthritis reactive	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Arthropathy	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Back pain	4/2263 (0.2%)		8/2285 (0.4%)		5/2170 (0.2%)		7/3348 (0.2%)		6/5777 (0.1%)
Bone pain	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bursitis	0/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		4/3348 (0.1%)		0/5777 (0%)
Cervical spinal stenosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		3/5777 (0.1%)
Chondromalacia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Chondropathy	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Compartment syndrome	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Costochondritis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Dactylitis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Dupuytren's contracture	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Exostosis	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Fasciitis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Finger deformity	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Flank pain	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Foot deformity	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Fracture malunion	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Gouty arthritis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gouty tophus	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Groin pain	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Haemarthrosis	1/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Immunoglobulin G4 related disease	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Intervertebral disc calcification	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Intervertebral disc compression	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Intervertebral disc degeneration	1/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		3/3348 (0.1%)		0/5777 (0%)
Intervertebral disc disorder	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Intervertebral disc displacement	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Intervertebral disc protrusion	4/2263 (0.2%)		2/2285 (0.1%)		6/2170 (0.3%)		10/3348 (0.3%)		6/5777 (0.1%)
Jaw cyst	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Joint instability	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Joint swelling	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Lumbar spinal stenosis	1/2263 (0%)		4/2285 (0.2%)		1/2170 (0%)		5/3348 (0.1%)		5/5777 (0.1%)
Meniscal degeneration	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Metatarsalgia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Muscle atrophy	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Muscle haemorrhage	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Muscle spasms	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Muscle swelling	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Muscular weakness	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Musculoskeletal chest pain	3/2263 (0.1%)		3/2285 (0.1%)		5/2170 (0.2%)		5/3348 (0.1%)		2/5777 (0%)
Musculoskeletal pain	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		4/3348 (0.1%)		4/5777 (0.1%)
Myalgia	1/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Myofascial pain syndrome	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Neck pain	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Neuropathic arthropathy	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Osteitis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Osteoarthritis	19/2263 (0.8%)		21/2285 (0.9%)		18/2170 (0.8%)		51/3348 (1.5%)		26/5777 (0.5%)
Osteochondrosis	1/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Osteolysis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Osteonecrosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Osteoporosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Osteoporotic fracture	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pain in extremity	5/2263 (0.2%)		1/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Pain in jaw	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pathological fracture	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Polyarthritis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Polymyalgia rheumatica	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Rhabdomyolysis	2/2263 (0.1%)		1/2285 (0%)		2/2170 (0.1%)		3/3348 (0.1%)		3/5777 (0.1%)
Rheumatoid arthritis	0/2263 (0%)		0/2285 (0%)		3/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Rotator cuff syndrome	2/2263 (0.1%)		0/2285 (0%)		2/2170 (0.1%)		5/3348 (0.1%)		3/5777 (0.1%)
Shoulder deformity	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Soft tissue mass	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Spinal column stenosis	6/2263 (0.3%)		2/2285 (0.1%)		4/2170 (0.2%)		4/3348 (0.1%)		4/5777 (0.1%)
Spinal deformity	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Spinal osteoarthritis	2/2263 (0.1%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Spinal pain	3/2263 (0.1%)		2/2285 (0.1%)		3/2170 (0.1%)		5/3348 (0.1%)		3/5777 (0.1%)
Spondylitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Spondylolisthesis	0/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		2/3348 (0.1%)		1/5777 (0%)
Synovial cyst	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Synovitis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Tendonitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Tenosynovitis	0/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		1/5777 (0%)
Trigger finger	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Vertebral foraminal stenosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Vertebral wedging	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Abdominal neoplasm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Acute leukaemia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Acute myeloid leukaemia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Adenocarcinoma	0/2263 (0%)		1/2285 (0%)		3/2170 (0.1%)		2/3348 (0.1%)		0/5777 (0%)
Adenocarcinoma gastric	0/2263 (0%)		2/2285 (0.1%)		2/2170 (0.1%)		3/3348 (0.1%)		0/5777 (0%)
Adenocarcinoma of colon	3/2263 (0.1%)		1/2285 (0%)		2/2170 (0.1%)		5/3348 (0.1%)		3/5777 (0.1%)
Adenocarcinoma pancreas	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Adenoma benign	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Adenosquamous cell lung cancer	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Adrenal adenoma	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Adrenal neoplasm	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Angiolipoma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Angiosarcoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
B-cell lymphoma	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Basal cell carcinoma	14/2263 (0.6%)		18/2285 (0.8%)		18/2170 (0.8%)		21/3348 (0.6%)		30/5777 (0.5%)
Benign cardiac neoplasm	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Benign gastric neoplasm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Benign lung neoplasm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Benign neoplasm	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Benign neoplasm of bladder	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Benign neoplasm of scrotum	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Benign neoplasm of skin	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Benign salivary gland neoplasm	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Benign small intestinal neoplasm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Benign urinary tract neoplasm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Bile duct cancer	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Bladder cancer	5/2263 (0.2%)		5/2285 (0.2%)		3/2170 (0.1%)		5/3348 (0.1%)		2/5777 (0%)
Bladder neoplasm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		3/5777 (0.1%)
Bladder papilloma	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bladder transitional cell carcinoma	3/2263 (0.1%)		2/2285 (0.1%)		2/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Bone cancer	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Bone cancer metastatic	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bowen's disease	3/2263 (0.1%)		1/2285 (0%)		2/2170 (0.1%)		3/3348 (0.1%)		1/5777 (0%)
Brain neoplasm	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Brain neoplasm malignant	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Breast cancer	4/2263 (0.2%)		0/2285 (0%)		5/2170 (0.2%)		2/3348 (0.1%)		4/5777 (0.1%)
Breast cancer female	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Breast cancer metastatic	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Brenner tumour	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bronchial carcinoma	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		3/5777 (0.1%)
Carcinoid tumour of the gastrointestinal tract	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Cervix carcinoma	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Cholangiocarcinoma	0/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Chronic lymphocytic leukaemia	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Clear cell renal cell carcinoma	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Colon adenoma	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Colon cancer	3/2263 (0.1%)		4/2285 (0.2%)		5/2170 (0.2%)		6/3348 (0.2%)		3/5777 (0.1%)
Colon neoplasm	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Colorectal adenocarcinoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Colorectal cancer	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Diffuse large B-cell lymphoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Diffuse large B-cell lymphoma stage IV	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Ductal adenocarcinoma of pancreas	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Endometrial adenocarcinoma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Endometrial cancer	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Endometrial cancer stage III	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Extranodal marginal zone B-cell lymphoma (MALT type)	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Fibroma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Fibrous histiocytoma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gallbladder adenocarcinoma	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Gastric adenoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Gastric cancer	5/2263 (0.2%)		1/2285 (0%)		1/2170 (0%)		5/3348 (0.1%)		5/5777 (0.1%)
Gastrointestinal carcinoma	1/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Gastrointestinal tract adenoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Glioblastoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Glioma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Haemangioma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hepatic cancer	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Hepatic cancer metastatic	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Hepatic cancer stage IV	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hepatic neoplasm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Hepatocellular carcinoma	1/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Hodgkin's disease	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hypergammaglobulinaemia benign monoclonal	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Inflammatory pseudotumour	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Intestinal adenocarcinoma	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Intraductal proliferative breast lesion	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Invasive breast carcinoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Invasive ductal breast carcinoma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Keratoacanthoma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Large intestine benign neoplasm	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Laryngeal cancer	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Laryngeal squamous cell carcinoma	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lentigo maligna	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Leukaemia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Lip and/or oral cavity cancer	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lip squamous cell carcinoma	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lipoma	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Liposarcoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Lung adenocarcinoma	0/2263 (0%)		3/2285 (0.1%)		3/2170 (0.1%)		7/3348 (0.2%)		1/5777 (0%)
Lung adenocarcinoma stage III	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lung adenocarcinoma stage IV	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lung cancer metastatic	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Lung carcinoma cell type unspecified recurrent	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Lung carcinoma cell type unspecified stage III	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lung neoplasm	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		2/5777 (0%)
Lung neoplasm malignant	4/2263 (0.2%)		9/2285 (0.4%)		9/2170 (0.4%)		25/3348 (0.7%)		14/5777 (0.2%)
Lung squamous cell carcinoma metastatic	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Lymphoma	1/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Lymphoproliferative disorder	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Malignant fibrous histiocytoma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Malignant mediastinal neoplasm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Malignant melanoma	2/2263 (0.1%)		5/2285 (0.2%)		3/2170 (0.1%)		2/3348 (0.1%)		4/5777 (0.1%)
Malignant melanoma in situ	2/2263 (0.1%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		1/5777 (0%)
Malignant neoplasm of pleura	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Malignant neoplasm of unknown primary site	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Malignant peritoneal neoplasm	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Malignant pleural effusion	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Mantle cell lymphoma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Medullary thyroid cancer	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Meningioma	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Meningioma benign	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Metastases to adrenals	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Metastases to bone	0/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		2/3348 (0.1%)		1/5777 (0%)
Metastases to central nervous system	0/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Metastases to kidney	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Metastases to liver	2/2263 (0.1%)		5/2285 (0.2%)		1/2170 (0%)		4/3348 (0.1%)		2/5777 (0%)
Metastases to lung	0/2263 (0%)		2/2285 (0.1%)		5/2170 (0.2%)		2/3348 (0.1%)		2/5777 (0%)
Metastases to lymph nodes	1/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		1/3348 (0%)		0/5777 (0%)
Metastases to pelvis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Metastases to pleura	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Metastases to rectum	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Metastases to spine	2/2263 (0.1%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Metastatic bronchial carcinoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Metastatic malignant melanoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Metastatic renal cell carcinoma	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Metastatic squamous cell carcinoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Monoclonal gammopathy	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Mucinous adenocarcinoma of appendix	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Mycosis fungoides	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Myelodysplastic syndrome	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Myelofibrosis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Nasal cavity cancer	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Neoplasm malignant	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Neoplasm skin	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Neuroendocrine breast tumour	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Neuroendocrine carcinoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Non-Hodgkin's lymphoma	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Non-Hodgkin's lymphoma refractory	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Non-small cell lung cancer	2/2263 (0.1%)		1/2285 (0%)		3/2170 (0.1%)		1/3348 (0%)		3/5777 (0.1%)
Non-small cell lung cancer metastatic	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Non-small cell lung cancer stage IV	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Oesophageal adenocarcinoma	0/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Oesophageal adenocarcinoma stage II	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Oesophageal cancer metastatic	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Oesophageal carcinoma	1/2263 (0%)		0/2285 (0%)		4/2170 (0.2%)		2/3348 (0.1%)		2/5777 (0%)
Oesophageal neoplasm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Oesophageal squamous cell carcinoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Oligodendroglioma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Oropharyngeal squamous cell carcinoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Ovarian adenoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Ovarian cancer	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Ovarian neoplasm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pancreatic carcinoma	1/2263 (0%)		4/2285 (0.2%)		3/2170 (0.1%)		5/3348 (0.1%)		3/5777 (0.1%)
Pancreatic carcinoma metastatic	2/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Papillary cystadenoma lymphomatosum	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Papillary renal cell carcinoma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Papillary thyroid cancer	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		2/5777 (0%)
Parathyroid tumour benign	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Penile cancer	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Phaeochromocytoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pharyngeal cancer	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pituitary tumour benign	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Plasma cell myeloma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Pleomorphic adenoma	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Polycythaemia vera	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Prostate cancer	12/2263 (0.5%)		10/2285 (0.4%)		10/2170 (0.5%)		13/3348 (0.4%)		15/5777 (0.3%)
Prostate cancer metastatic	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Prostate cancer recurrent	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Prostatic adenoma	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Rectal adenocarcinoma	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Rectal adenoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Rectal cancer	4/2263 (0.2%)		2/2285 (0.1%)		2/2170 (0.1%)		3/3348 (0.1%)		1/5777 (0%)
Rectal cancer metastatic	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Rectosigmoid cancer	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Renal cancer	2/2263 (0.1%)		2/2285 (0.1%)		3/2170 (0.1%)		2/3348 (0.1%)		1/5777 (0%)
Renal cancer metastatic	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Renal cell carcinoma	2/2263 (0.1%)		1/2285 (0%)		5/2170 (0.2%)		1/3348 (0%)		3/5777 (0.1%)
Renal neoplasm	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Renal oncocytoma	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Rosai-Dorfman syndrome	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Salivary gland adenoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Salivary gland neoplasm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Seborrhoeic keratosis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Skin cancer	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Small cell lung cancer	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		5/3348 (0.1%)		1/5777 (0%)
Small cell lung cancer metastatic	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Small intestine adenocarcinoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Small intestine carcinoma	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Small intestine carcinoma metastatic	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Squamous cell carcinoma	12/2263 (0.5%)		5/2285 (0.2%)		6/2170 (0.3%)		10/3348 (0.3%)		9/5777 (0.2%)
Squamous cell carcinoma of lung	2/2263 (0.1%)		5/2285 (0.2%)		0/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Squamous cell carcinoma of skin	3/2263 (0.1%)		2/2285 (0.1%)		1/2170 (0%)		3/3348 (0.1%)		1/5777 (0%)
Squamous cell carcinoma of the hypopharynx	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Squamous cell carcinoma of the tongue	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Superficial spreading melanoma stage II	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Testis cancer	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Throat cancer	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Thyroid cancer	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Thyroid cancer metastatic	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Thyroid neoplasm	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Tongue neoplasm malignant stage unspecified	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Tonsil cancer metastatic	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Transitional cell carcinoma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		4/5777 (0.1%)
Transitional cell carcinoma urethra	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Tumour perforation	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Uterine cancer	0/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		1/3348 (0%)		0/5777 (0%)
Uterine leiomyoma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Nervous system disorders
Amnesia	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Amyotrophic lateral sclerosis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Aphasia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Apraxia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Ataxia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Balance disorder	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Brain injury	0/2263 (0%)		3/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Brain oedema	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Carotid arteriosclerosis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Carotid artery aneurysm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Carotid artery disease	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Carotid artery occlusion	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Carotid artery stenosis	3/2263 (0.1%)		0/2285 (0%)		2/2170 (0.1%)		1/3348 (0%)		8/5777 (0.1%)
Carpal tunnel syndrome	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		3/5777 (0.1%)
Cauda equina syndrome	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Cerebellar infarction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Cerebellar stroke	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Cerebral arteriosclerosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Cerebral haemorrhage	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Cerebral infarction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		9/5777 (0.2%)
Cerebral ischaemia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		3/5777 (0.1%)
Cerebrovascular accident	2/2263 (0.1%)		1/2285 (0%)		1/2170 (0%)		4/3348 (0.1%)		22/5777 (0.4%)
Cervical myelopathy	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Cervical radiculopathy	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Cervicobrachial syndrome	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Cognitive disorder	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Coma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Dementia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Dementia Alzheimer's type	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Dementia with Lewy bodies	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Depressed level of consciousness	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Diabetic coma	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Diabetic neuropathy	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Diplegia	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Dizziness	6/2263 (0.3%)		2/2285 (0.1%)		3/2170 (0.1%)		7/3348 (0.2%)		4/5777 (0.1%)
Dysaesthesia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Dysarthria	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Dystonia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Embolic stroke	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Encephalopathy	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		3/5777 (0.1%)
Epilepsy	2/2263 (0.1%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Facial paralysis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Focal dyscognitive seizures	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Generalised tonic-clonic seizure	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Guillain-Barre syndrome	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Haemorrhage intracranial	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Haemorrhagic stroke	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Haemorrhagic transformation stroke	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Headache	4/2263 (0.2%)		3/2285 (0.1%)		3/2170 (0.1%)		4/3348 (0.1%)		0/5777 (0%)
Hemiparesis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hydrocephalus	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hypersomnia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hypertensive encephalopathy	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Hypoaesthesia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Hypoglycaemic coma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hypoglycaemic encephalopathy	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hypoxic-ischaemic encephalopathy	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		2/5777 (0%)
IIIrd nerve paresis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Intracranial aneurysm	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Intracranial pressure increased	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Ischaemic stroke	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		16/5777 (0.3%)
Lacunar infarction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Lacunar stroke	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Loss of consciousness	1/2263 (0%)		3/2285 (0.1%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Lumbar radiculopathy	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Lumbosacral radiculopathy	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Mental impairment	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Metabolic encephalopathy	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Migraine	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Mixed dementia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Nerve compression	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Neuralgia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Neuropathy peripheral	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Normal pressure hydrocephalus	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Optic neuritis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Orthostatic intolerance	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Paraesthesia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Paralysis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Paresis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Partial seizures	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Peripheral nerve lesion	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Polyneuropathy	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Post herpetic neuralgia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Post stroke seizure	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Presyncope	2/2263 (0.1%)		1/2285 (0%)		2/2170 (0.1%)		4/3348 (0.1%)		2/5777 (0%)
Restless legs syndrome	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Sciatica	0/2263 (0%)		0/2285 (0%)		5/2170 (0.2%)		4/3348 (0.1%)		0/5777 (0%)
Seizure	3/2263 (0.1%)		2/2285 (0.1%)		1/2170 (0%)		4/3348 (0.1%)		2/5777 (0%)
Sensory disturbance	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Spinal claudication	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Spinal cord compression	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Spinal cord infarction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Spondylitic myelopathy	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Status epilepticus	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Stupor	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Subdural hygroma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Syncope	15/2263 (0.7%)		17/2285 (0.7%)		16/2170 (0.7%)		25/3348 (0.7%)		16/5777 (0.3%)
Tension headache	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Thalamic infarction	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Thrombotic cerebral infarction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Tonic convulsion	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Toxic encephalopathy	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Transient global amnesia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Transient ischaemic attack	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		15/5777 (0.3%)
Trigeminal neuralgia	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Upper motor neurone lesion	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
VIth nerve paralysis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Vascular dementia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Vascular encephalopathy	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Vertebrobasilar insufficiency	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Product Issues
Device battery issue	2/2263 (0.1%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		1/5777 (0%)
Device dislocation	0/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		1/3348 (0%)		1/5777 (0%)
Device end of service	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Device failure	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Device inappropriate shock delivery	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Device issue	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Device lead damage	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Device lead issue	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Device loosening	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Device malfunction	1/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Device occlusion	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Device signal detection issue	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Lead dislodgement	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Psychiatric disorders
Acute stress disorder	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Adjustment disorder	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Affective disorder	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Alcoholic psychosis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Alcoholism	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Anxiety	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		3/3348 (0.1%)		2/5777 (0%)
Anxiety disorder	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Anxiety disorder due to a general medical condition	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bipolar I disorder	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bipolar disorder	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Burnout syndrome	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Completed suicide	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Confusional state	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Conversion disorder	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Delirium	1/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		2/3348 (0.1%)		2/5777 (0%)
Delirium tremens	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Depression	7/2263 (0.3%)		4/2285 (0.2%)		2/2170 (0.1%)		4/3348 (0.1%)		2/5777 (0%)
Dissociative amnesia	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Drug use disorder	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Generalised anxiety disorder	2/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hallucination, visual	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Head banging	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Homicidal ideation	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Insomnia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Intentional self-injury	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Major depression	2/2263 (0.1%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Mental status changes	4/2263 (0.2%)		0/2285 (0%)		2/2170 (0.1%)		6/3348 (0.2%)		2/5777 (0%)
Panic attack	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Personality change	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Psychotic disorder	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Psychotic disorder due to a general medical condition	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Restlessness	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Schizophrenia	0/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Somnambulism	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Suicidal ideation	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Suicide attempt	1/2263 (0%)		1/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Renal and urinary disorders
Acute kidney injury	20/2263 (0.9%)		30/2285 (1.3%)		16/2170 (0.7%)		27/3348 (0.8%)		22/5777 (0.4%)
Acute prerenal failure	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Anuria	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Azotaemia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Calculus bladder	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		3/5777 (0.1%)
Calculus urethral	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Calculus urinary	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Chronic kidney disease	4/2263 (0.2%)		5/2285 (0.2%)		4/2170 (0.2%)		4/3348 (0.1%)		5/5777 (0.1%)
Diabetic nephropathy	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Dysuria	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
End stage renal disease	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Focal segmental glomerulosclerosis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Glomerulonephritis membranous	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Haematuria	5/2263 (0.2%)		6/2285 (0.3%)		3/2170 (0.1%)		7/3348 (0.2%)		3/5777 (0.1%)
Hydronephrosis	2/2263 (0.1%)		3/2285 (0.1%)		1/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Hypertensive nephropathy	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lower urinary tract symptoms	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Nephrolithiasis	3/2263 (0.1%)		2/2285 (0.1%)		4/2170 (0.2%)		7/3348 (0.2%)		3/5777 (0.1%)
Nephrotic syndrome	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Obstructive uropathy	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pollakiuria	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Polyuria	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Prerenal failure	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Renal artery stenosis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Renal artery thrombosis	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Renal colic	1/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Renal cyst	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Renal failure	7/2263 (0.3%)		10/2285 (0.4%)		11/2170 (0.5%)		13/3348 (0.4%)		5/5777 (0.1%)
Renal haematoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Renal impairment	1/2263 (0%)		4/2285 (0.2%)		3/2170 (0.1%)		1/3348 (0%)		4/5777 (0.1%)
Renal injury	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Renal mass	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Renal tubular necrosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Stress urinary incontinence	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Tubulointerstitial nephritis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Ureteric obstruction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Ureteric stenosis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Ureterolithiasis	1/2263 (0%)		1/2285 (0%)		2/2170 (0.1%)		7/3348 (0.2%)		3/5777 (0.1%)
Urethral obstruction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Urinary bladder haemorrhage	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Urinary bladder polyp	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Urinary incontinence	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Urinary retention	4/2263 (0.2%)		4/2285 (0.2%)		3/2170 (0.1%)		4/3348 (0.1%)		6/5777 (0.1%)
Urinary tract obstruction	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Vesicocutaneous fistula	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Reproductive system and breast disorders
Balanoposthitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Benign prostatic hyperplasia	5/2263 (0.2%)		6/2285 (0.3%)		5/2170 (0.2%)		5/3348 (0.1%)		8/5777 (0.1%)
Cystocele	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Dysmenorrhoea	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Endometrial hyperplasia	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Epididymal cyst	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Erectile dysfunction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Female genital tract fistula	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Genital atrophy	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Genital prolapse	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Menorrhagia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Ovarian cyst	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pelvic pain	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Postmenopausal haemorrhage	2/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Prostatic haemorrhage	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Prostatic mass	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Prostatism	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Prostatitis	2/2263 (0.1%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		0/5777 (0%)
Prostatomegaly	0/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Rectocele	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Spermatocele	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Uterine cervix stenosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Uterine prolapse	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Vaginal haemorrhage	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Varicocele	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Varicose veins pelvic	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/2263 (0%)		3/2285 (0.1%)		4/2170 (0.2%)		4/3348 (0.1%)		2/5777 (0%)
Acute respiratory distress syndrome	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Acute respiratory failure	10/2263 (0.4%)		7/2285 (0.3%)		11/2170 (0.5%)		13/3348 (0.4%)		21/5777 (0.4%)
Alveolitis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Alveolitis allergic	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Asphyxia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Asthma	7/2263 (0.3%)		2/2285 (0.1%)		0/2170 (0%)		3/3348 (0.1%)		2/5777 (0%)
Atelectasis	3/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		0/5777 (0%)
Bronchial hyperreactivity	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Bronchial obstruction	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bronchiectasis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Bronchitis chronic	2/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Bronchospasm	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		1/5777 (0%)
Cheyne-Stokes respiration	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Chronic obstructive pulmonary disease	28/2263 (1.2%)		21/2285 (0.9%)		16/2170 (0.7%)		40/3348 (1.2%)		33/5777 (0.6%)
Cough	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		1/5777 (0%)
Dyspnoea	14/2263 (0.6%)		8/2285 (0.4%)		10/2170 (0.5%)		23/3348 (0.7%)		19/5777 (0.3%)
Dyspnoea exertional	2/2263 (0.1%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Dyspnoea paroxysmal nocturnal	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Emphysema	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Epistaxis	3/2263 (0.1%)		2/2285 (0.1%)		2/2170 (0.1%)		6/3348 (0.2%)		2/5777 (0%)
Haemoptysis	2/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		4/3348 (0.1%)		1/5777 (0%)
Haemothorax	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hiccups	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Hydrothorax	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Hypopnoea	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hypoxia	3/2263 (0.1%)		1/2285 (0%)		1/2170 (0%)		3/3348 (0.1%)		5/5777 (0.1%)
Idiopathic interstitial pneumonia	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Idiopathic pneumonia syndrome	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Idiopathic pulmonary fibrosis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Interstitial lung disease	3/2263 (0.1%)		1/2285 (0%)		2/2170 (0.1%)		2/3348 (0.1%)		1/5777 (0%)
Laryngeal oedema	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Laryngospasm	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lung consolidation	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lung hernia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Lung infiltration	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Nasal obstruction	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Nasal polyps	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Nasal turbinate hypertrophy	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Obstructive airways disorder	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Organising pneumonia	2/2263 (0.1%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Oropharyngeal pain	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pickwickian syndrome	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pleural adhesion	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pleural effusion	8/2263 (0.4%)		5/2285 (0.2%)		4/2170 (0.2%)		6/3348 (0.2%)		4/5777 (0.1%)
Pleurisy	1/2263 (0%)		3/2285 (0.1%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pleuritic pain	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pneumomediastinum	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pneumonia aspiration	1/2263 (0%)		4/2285 (0.2%)		0/2170 (0%)		3/3348 (0.1%)		1/5777 (0%)
Pneumonitis	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pneumothorax	5/2263 (0.2%)		2/2285 (0.1%)		0/2170 (0%)		4/3348 (0.1%)		1/5777 (0%)
Pneumothorax spontaneous	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Productive cough	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pulmonary alveolar haemorrhage	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pulmonary arterial hypertension	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pulmonary congestion	2/2263 (0.1%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Pulmonary embolism	1/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		2/3348 (0.1%)		18/5777 (0.3%)
Pulmonary fibrosis	3/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		4/3348 (0.1%)		1/5777 (0%)
Pulmonary haematoma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Pulmonary hypertension	2/2263 (0.1%)		3/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pulmonary mass	1/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		0/3348 (0%)		3/5777 (0.1%)
Pulmonary microemboli	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Pulmonary oedema	4/2263 (0.2%)		4/2285 (0.2%)		1/2170 (0%)		2/3348 (0.1%)		5/5777 (0.1%)
Pulmonary sarcoidosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Respiratory alkalosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Respiratory arrest	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Respiratory distress	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		0/3348 (0%)		3/5777 (0.1%)
Respiratory failure	12/2263 (0.5%)		11/2285 (0.5%)		9/2170 (0.4%)		12/3348 (0.4%)		5/5777 (0.1%)
Respiratory tract inflammation	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Respiratory tract irritation	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Rhinitis allergic	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Sinus congestion	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Sinus polyp	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Sleep apnoea syndrome	2/2263 (0.1%)		2/2285 (0.1%)		0/2170 (0%)		5/3348 (0.1%)		2/5777 (0%)
Status asthmaticus	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Vocal cord leukoplakia	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Wheezing	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Skin and subcutaneous tissue disorders
Acne	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Actinic keratosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Angioedema	1/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		3/3348 (0.1%)		1/5777 (0%)
Blister	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Brow ptosis	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Decubitus ulcer	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		2/5777 (0%)
Dermatitis	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Dermatitis allergic	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Diabetic foot	1/2263 (0%)		6/2285 (0.3%)		1/2170 (0%)		0/3348 (0%)		4/5777 (0.1%)
Eczema	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Erythema	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hyperhidrosis	0/2263 (0%)		2/2285 (0.1%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Hyperkeratosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Hypersensitivity vasculitis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Neurodermatitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Prurigo	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Pruritus allergic	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Psoriasis	1/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		1/5777 (0%)
Rhinophyma	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Skin ulcer	0/2263 (0%)		5/2285 (0.2%)		5/2170 (0.2%)		3/3348 (0.1%)		1/5777 (0%)
Stasis dermatitis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		0/5777 (0%)
Stevens-Johnson syndrome	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Subcutaneous emphysema	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Urticaria	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Social circumstances
Homicide	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Vascular disorders
Accelerated hypertension	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Aneurysm ruptured	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Angiodysplasia	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Aortic aneurysm	8/2263 (0.4%)		4/2285 (0.2%)		6/2170 (0.3%)		6/3348 (0.2%)		12/5777 (0.2%)
Aortic aneurysm rupture	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		3/5777 (0.1%)
Aortic dissection	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Aortic stenosis	1/2263 (0%)		0/2285 (0%)		2/2170 (0.1%)		0/3348 (0%)		1/5777 (0%)
Aortitis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Arterial haemorrhage	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Arterial insufficiency	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Arteriosclerosis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		2/3348 (0.1%)		5/5777 (0.1%)
Arteriovenous fistula	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Arteritis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Brachiocephalic artery stenosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Circulatory collapse	3/2263 (0.1%)		1/2285 (0%)		3/2170 (0.1%)		1/3348 (0%)		2/5777 (0%)
Deep vein thrombosis	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		5/5777 (0.1%)
Embolism	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Embolism arterial	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Embolism venous	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Essential hypertension	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Extremity necrosis	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		2/3348 (0.1%)		2/5777 (0%)
Femoral artery aneurysm	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Femoral artery embolism	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Haematoma	2/2263 (0.1%)		3/2285 (0.1%)		1/2170 (0%)		5/3348 (0.1%)		5/5777 (0.1%)
Haemodynamic instability	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Haemorrhage	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Hypertension	10/2263 (0.4%)		8/2285 (0.4%)		8/2170 (0.4%)		15/3348 (0.4%)		17/5777 (0.3%)
Hypertensive crisis	7/2263 (0.3%)		5/2285 (0.2%)		2/2170 (0.1%)		11/3348 (0.3%)		5/5777 (0.1%)
Hypertensive emergency	1/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Hypotension	8/2263 (0.4%)		5/2285 (0.2%)		4/2170 (0.2%)		11/3348 (0.3%)		6/5777 (0.1%)
Hypovolaemic shock	2/2263 (0.1%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Intermittent claudication	1/2263 (0%)		1/2285 (0%)		0/2170 (0%)		3/3348 (0.1%)		3/5777 (0.1%)
Internal haemorrhage	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Ischaemic limb pain	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lymphatic fistula	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Lymphorrhoea	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Malignant hypertension	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Orthostatic hypertension	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Orthostatic hypotension	1/2263 (0%)		3/2285 (0.1%)		1/2170 (0%)		0/3348 (0%)		2/5777 (0%)
Pallor	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Peripheral arterial occlusive disease	3/2263 (0.1%)		4/2285 (0.2%)		2/2170 (0.1%)		4/3348 (0.1%)		11/5777 (0.2%)
Peripheral artery aneurysm	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Peripheral artery occlusion	0/2263 (0%)		3/2285 (0.1%)		2/2170 (0.1%)		0/3348 (0%)		4/5777 (0.1%)
Peripheral artery stenosis	1/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		6/5777 (0.1%)
Peripheral artery thrombosis	0/2263 (0%)		2/2285 (0.1%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Peripheral embolism	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Peripheral ischaemia	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		11/5777 (0.2%)
Peripheral vascular disorder	0/2263 (0%)		3/2285 (0.1%)		2/2170 (0.1%)		1/3348 (0%)		4/5777 (0.1%)
Peripheral venous disease	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Shock	0/2263 (0%)		0/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Shock haemorrhagic	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Temporal arteritis	1/2263 (0%)		0/2285 (0%)		1/2170 (0%)		1/3348 (0%)		1/5777 (0%)
Thrombophlebitis	0/2263 (0%)		1/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Thrombophlebitis superficial	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Thrombosis	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		1/5777 (0%)
Varicose ulceration	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Varicose vein	0/2263 (0%)		1/2285 (0%)		1/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Vascular insufficiency	0/2263 (0%)		0/2285 (0%)		0/2170 (0%)		1/3348 (0%)		0/5777 (0%)
Venous thrombosis limb	1/2263 (0%)		0/2285 (0%)		0/2170 (0%)		0/3348 (0%)		0/5777 (0%)
Other (Not Including Serious) Adverse Events
	Group I		Group II		Group III		Group IV		Group V
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1271/2263 (56.2%)		1324/2285 (57.9%)		1199/2170 (55.3%)		1905/3348 (56.9%)		1497/5777 (25.9%)
Cardiac disorders
Angina pectoris	142/2263 (6.3%)		164/2285 (7.2%)		129/2170 (5.9%)		228/3348 (6.8%)		115/5777 (2%)
Gastrointestinal disorders
Diarrhoea	138/2263 (6.1%)		146/2285 (6.4%)		137/2170 (6.3%)		216/3348 (6.5%)		110/5777 (1.9%)
General disorders
Fatigue	113/2263 (5%)		99/2285 (4.3%)		84/2170 (3.9%)		169/3348 (5%)		72/5777 (1.2%)
Non-cardiac chest pain	142/2263 (6.3%)		143/2285 (6.3%)		111/2170 (5.1%)		228/3348 (6.8%)		68/5777 (1.2%)
Oedema peripheral	136/2263 (6%)		142/2285 (6.2%)		134/2170 (6.2%)		173/3348 (5.2%)		110/5777 (1.9%)
Infections and infestations
Bronchitis	131/2263 (5.8%)		162/2285 (7.1%)		114/2170 (5.3%)		234/3348 (7%)		160/5777 (2.8%)
Influenza	141/2263 (6.2%)		145/2285 (6.3%)		118/2170 (5.4%)		194/3348 (5.8%)		154/5777 (2.7%)
Upper respiratory tract infection	153/2263 (6.8%)		156/2285 (6.8%)		134/2170 (6.2%)		252/3348 (7.5%)		125/5777 (2.2%)
Urinary tract infection	126/2263 (5.6%)		129/2285 (5.6%)		93/2170 (4.3%)		175/3348 (5.2%)		123/5777 (2.1%)
Viral upper respiratory tract infection	264/2263 (11.7%)		297/2285 (13%)		263/2170 (12.1%)		388/3348 (11.6%)		16/5777 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	165/2263 (7.3%)		181/2285 (7.9%)		144/2170 (6.6%)		252/3348 (7.5%)		184/5777 (3.2%)
Back pain	169/2263 (7.5%)		177/2285 (7.7%)		157/2170 (7.2%)		277/3348 (8.3%)		163/5777 (2.8%)
Pain in extremity	145/2263 (6.4%)		145/2285 (6.3%)		98/2170 (4.5%)		204/3348 (6.1%)		128/5777 (2.2%)
Nervous system disorders
Dizziness	114/2263 (5%)		126/2285 (5.5%)		132/2170 (6.1%)		189/3348 (5.6%)		107/5777 (1.9%)
Headache	133/2263 (5.9%)		111/2285 (4.9%)		120/2170 (5.5%)		178/3348 (5.3%)		72/5777 (1.2%)
Respiratory, thoracic and mediastinal disorders
Cough	151/2263 (6.7%)		152/2285 (6.7%)		121/2170 (5.6%)		233/3348 (7%)		103/5777 (1.8%)
Dyspnoea	126/2263 (5.6%)		123/2285 (5.4%)		110/2170 (5.1%)		193/3348 (5.8%)		112/5777 (1.9%)
Vascular disorders
Hypertension	198/2263 (8.7%)		216/2285 (9.5%)		208/2170 (9.6%)		309/3348 (9.2%)		241/5777 (4.2%)

Limitations/Caveats

Comparison across groups is no longer feasible in the Extension phase because all patients received canakinumab 150 mg. Beyond the primary endpoint, all p-values for the canakinumab 50 mg and 300 mg groups are to be considered nominal only.

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.

Results Point of Contact

Name/Title	Study Director
Organization	Novartis Pharmaceuticals
Phone	862-778-8300
Email	Novartis.email@novartis.com

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT01327846

Other Study ID Numbers:

CACZ885M2301
2010-022970-14

First Posted:

Apr 4, 2011

Last Update Posted:

Jan 22, 2020

Last Verified:

Jan 1, 2020

CANTOS: Cardiovascular Risk Reduction Study (Reduction in Recurrent Major CV Disease Events)

Study Details

Study Description

Brief Summary

Detailed Description

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

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Main Study Inclusion Criteria:

Substudy 1 Inclusion:

Substudy 2 Inclusion:

Main Study Exclusion Criteria:

Contacts and Locations

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Sponsors and Collaborators

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Study Documents (Full-Text)

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Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Statistical Analysis 6

Statistical Analysis 7

Statistical Analysis 8

Statistical Analysis 9

Statistical Analysis 10

Statistical Analysis 11

Statistical Analysis 12

Statistical Analysis 13

Statistical Analysis 14

Statistical Analysis 15

Statistical Analysis 16

Statistical Analysis 17

Statistical Analysis 18

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Statistical Analysis 6

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Outcome Measure Data

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Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events