SUSTAIN™ 6: Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes
Study Details
Study Description
Brief Summary
This trial is conducted globally. The aim of the trial is to evaluate cardiovascular and other long-term outcomes with semaglutide in subjects with type 2 diabetes. The trial is event-driven, i.e. the maximum trial duration (up to max. 148 weeks) will depend on the accrual of major adverse cardiovascular events (MACE) in this trial and the remaining research programme. The incidence of MACE will be monitored throughout the trial which will be terminated according to plan when pre-specified stopping criteria are met.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Semaglutide 0.5 mg
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Drug: semaglutide
Once weekly doses of 0.5 mg semaglutide after an initial dose escalation step of 0.25 mg as an add-on to the standard-of-care treatment. Administered subcutaneously (s.c., under the skin)
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Experimental: Semaglutide 1.0 mg
|
Drug: semaglutide
Once weekly doses of 1.0 mg semaglutide after an initial dose escalation step of 0.25 mg followed by 0.5 mg dose escalation as an add-on to the standard-of-care treatment. Administered subcutaneously (s.c., under the skin)
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Placebo Comparator: Semaglutide placebo 0.5 mg
|
Drug: placebo
Once weekly doses volume-matched placebo, as an add-on to the standard-of-care treatment. Administered subcutaneously (s.c., under the skin).
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Placebo Comparator: Semaglutide placebo 1.0 mg
|
Drug: placebo
Once weekly doses volume-matched placebo, as an add-on to the standard-of-care treatment. Administered subcutaneously (s.c., under the skin).
|
Outcome Measures
Primary Outcome Measures
- Time From Randomisation to First Occurrence of a MACE, Defined as Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke [Time from randomisation up to end of follow-up (scheduled at week 109)]
Percentage of subjects experiencing a first event of a major adverse cardiovascular event (MACE), defined as cardiovascular (CV) death, non-fatal myocardial infarction (MI), or non-fatal stroke.
Secondary Outcome Measures
- Time From Randomisation to First Occurrence of an Expanded Composite Cardiovascular Outcome [Time from randomisation up to end of follow-up (scheduled at week 109)]
Percentage of subjects experiencing first occurrence of an expanded composite CV outcome (defined as either MACE, revascularisation [coronary and peripheral], unstable angina requiring hospitalisation or hospitalisation for heart failure)
- Time From Randomisation to Each Individual Component of the Expanded Composite Cardiovascular Outcome [Time from randomisation up to end of follow-up (scheduled at week 109)]
Percentage of subjects experiencing an event onset for each individual component of the expanded composite cardiovascular outcomes (defined as either MACE, revascularisation [coronary and peripheral], unstable angina requiring hospitalisation or hospitalisation for heart failure).
- Time From Randomisation to First Occurrence of All-cause Death, Non-fatal MI, or Non-fatal Stroke [Time from randomisation up to end of follow-up (scheduled at week 109)]
Percentage of subjects experiencing a first occurrence of all-cause death, non-fatal MI, or non-fatal stroke.
- Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Glycosylated Haemoglobin (HbA1c) [Week 0, up to week 104]
Estimated mean change from baseline in glycosylated haemoglobin (HbA1c) to last assessment in the trial during the treatment period.
- Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Fasting Plasma Glucose [Week 0, up to week 104]
Estimated mean change from baseline to last assessment in fasting plasma glucose in the trial during the treatment period.
- Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Body Weight [Week 0, up to week 104]
Estimated mean change from baseline to last assessment in body weight in the trial during the treatment period.
- Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profile [Week 0, up to week 104]
Estimated ratio to baseline at week 104 during the treatment period in lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides).
- Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Urinary Albumin to Creatinine Ratio [Week 0, up to week 104]
Estimated ratio to baseline in urinary albumin to creatinine ratio at week 104 during the treatment period.
- Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital Signs [Week 0, up to week 104]
Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (diastolic blood pressure and systolic blood pressure).
- Incidence During the Trial in Other Treatment Outcomes: Hypoglycaemic Events [Week 0 - 109]
Rates (event rate per 100 exposure years) of severe or blood glucose confirmed symptomatic hypoglycaemia defned as an episode that was severe according to the American diabetic association (ADA) classification or blood glucose (BG) confirmed by a PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
- Incidence During the Trial in Other Treatment Outcomes: Adverse Events [Weeks 0-109]
Rates (event rate per 100 years of exposure) of treatment emergent adverse events.
- Occurrence During the Trial in Other Treatment Outcomes: Anti-semaglutide Antibodies [Weeks 0-109]
The percentage of subjects that tested positive for anti-semaglutide antibodies at any time point post-baseline during the trial, from week 0 to week 109.
- Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Patient Reported Outcome (PRO) [Week 0, up to week 104]
Estimated mean change from baseline to last assessment in the trial in patient reported outcomes (PRO). PRO questionnaire (SF-36v2TM) measured the individual overall health related quality of life namely bodily pain, general health, mental component summary, mental health, physical component summary, physical functioning, role-emotional, role-physical, social functioning and vitality. The PRO scores were transformed to a 0-100 scale with higher scores indicating greater health related quality of life.
- Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profile (Free Fatty Acids) [Week 0, up to week 104]
Estimated ratio to baseline at week 104 during the treatment period in lipid profile (free fatty acids).
- Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital Signs (Pulse Rate) [Week 0, up to week 104]
Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (pulse rate).
Eligibility Criteria
Criteria
Inclusion Criteria: - Men and women with type 2 diabetes mellitus - Age above or equal to 50 years at screening and clinical evidence of cardiovascular disease or age above or equal to 60 years at screening and subclinical evidence of cardiovascular disease - Anti-diabetic drug naïve, or treated with one or two oral antidiabetic drug (OADs), or treated with human Neutral Protamin Hagedorn (NPH) insulin or long-acting insulin analogue or pre-mixed insulin, both types of insulin either alone or in combination with one or two OADs - HbA1c above or equal to 7.0% at screening Exclusion Criteria: - Type 1 diabetes mellitus - Use of glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide, or other) or pramlintide within 90 days prior to screening - Use of any dipeptidyl peptidase 4 (DPP-IV) inhibitor within 30 days prior to screening - Treatment with insulin other than basal and pre-mixed insulin within 90 days prior to screening - except for short-term use in connection with intercurrent illness - Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent acute complications of diabetes (eg diabetes ketoacidosis) within 90 days prior to screening - History of chronic pancreatitis or idiopathic acute pancreatitis - Acute coronary or cerebro-vascular event within 90 days prior to randomisation - Currently planned coronary, carotid or peripheral artery revascularisation - Chronic heart failure New York Heart Association (NYHA) class IV - Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma - Personal history of non-familial medullary thyroid carcinoma
- Screening calcitonin above or equal to 50 ng/L
Contacts and Locations
Locations
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177 | Novo Nordisk Investigational Site | Holon | Israel | 58100 | |
178 | Novo Nordisk Investigational Site | Jerusalem | Israel | 91120 | |
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180 | Novo Nordisk Investigational Site | Petah-Tikva | Israel | 49100 | |
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189 | Novo Nordisk Investigational Site | Kota Samarahan | Malaysia | 94300 | |
190 | Novo Nordisk Investigational Site | Kuala Lumpur | Malaysia | 59100 | |
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198 | Novo Nordisk Investigational Site | Cuernavaca | Morelos | Mexico | 62250 |
199 | Novo Nordisk Investigational Site | Mexico City | México, D.F. | Mexico | 03300 |
200 | Novo Nordisk Investigational Site | Mexico City | México, D.F. | Mexico | 14000 |
201 | Novo Nordisk Investigational Site | México D.F. | México, D.F. | Mexico | 11550 |
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203 | Novo Nordisk Investigational Site | Aguascalientes | Mexico | 20230 | |
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210 | Novo Nordisk Investigational Site | Arkhangelsk | Russian Federation | 163001 | |
211 | Novo Nordisk Investigational Site | Arkhangelsk | Russian Federation | 163045 | |
212 | Novo Nordisk Investigational Site | Barnaul | Russian Federation | 656045 | |
213 | Novo Nordisk Investigational Site | Kazan | Russian Federation | 420043 | |
214 | Novo Nordisk Investigational Site | Moscow | Russian Federation | 117997 | |
215 | Novo Nordisk Investigational Site | Moscow | Russian Federation | 119435 | |
216 | Novo Nordisk Investigational Site | Novosibirsk | Russian Federation | 630047 | |
217 | Novo Nordisk Investigational Site | Penza | Russian Federation | 440026 | |
218 | Novo Nordisk Investigational Site | Saint-Petersburg | Russian Federation | 199034 | |
219 | Novo Nordisk Investigational Site | Saratov | Russian Federation | 410031 | |
220 | Novo Nordisk Investigational Site | Saratov | Russian Federation | 410053 | |
221 | Novo Nordisk Investigational Site | Smolensk | Russian Federation | 214019 | |
222 | Novo Nordisk Investigational Site | Yaroslavl | Russian Federation | 150062 | |
223 | Novo Nordisk Investigational Site | Almería | Spain | 04001 | |
224 | Novo Nordisk Investigational Site | Antequera | Spain | 29200 | |
225 | Novo Nordisk Investigational Site | Pozuelo de Alarcon | Spain | 28223 | |
226 | Novo Nordisk Investigational Site | Sanlúcar De Barrameda - Cádiz- | Spain | 15540 | |
227 | Novo Nordisk Investigational Site | Sevilla | Spain | 41010 | |
228 | Novo Nordisk Investigational Site | Vic (Barcelona) | Spain | 08500 | |
229 | Novo Nordisk Investigational Site | Chiayi City | Taiwan | 600 | |
230 | Novo Nordisk Investigational Site | Tainan city | Taiwan | 710 | |
231 | Novo Nordisk Investigational Site | Taipei | Taiwan | 114 | |
232 | Novo Nordisk Investigational Site | Taoyuan | Taiwan | 333 | |
233 | Novo Nordisk Investigational Site | Bangkok | Thailand | 10330 | |
234 | Novo Nordisk Investigational Site | Bangkok | Thailand | 10400 | |
235 | Novo Nordisk Investigational Site | Bangkok | Thailand | 10700 | |
236 | Novo Nordisk Investigational Site | Ankara | Turkey | 06100 | |
237 | Novo Nordisk Investigational Site | Ankara | Turkey | 06110 | |
238 | Novo Nordisk Investigational Site | Antalya | Turkey | 07058 | |
239 | Novo Nordisk Investigational Site | Canakkale | Turkey | 17020 | |
240 | Novo Nordisk Investigational Site | Denizli | Turkey | 20070 | |
241 | Novo Nordisk Investigational Site | Istanbul | Turkey | 34096 | |
242 | Novo Nordisk Investigational Site | Istanbul | Turkey | 34722 | |
243 | Novo Nordisk Investigational Site | Istanbul | Turkey | 34890 | |
244 | Novo Nordisk Investigational Site | Izmir | Turkey | 35340 | |
245 | Novo Nordisk Investigational Site | Kocaeli | Turkey | 41380 | |
246 | Novo Nordisk Investigational Site | Aberdeen | United Kingdom | AB25 2ZD | |
247 | Novo Nordisk Investigational Site | Birmingham | United Kingdom | B9 5SS | |
248 | Novo Nordisk Investigational Site | Leeds | United Kingdom | LS25 1AN | |
249 | Novo Nordisk Investigational Site | Liverpool | United Kingdom | L9 7AL | |
250 | Novo Nordisk Investigational Site | Northwood | United Kingdom | HA6 2RN | |
251 | Novo Nordisk Investigational Site | Sidcup | United Kingdom | DA14 6LT | |
252 | Novo Nordisk Investigational Site | Swansea | United Kingdom | SA6 6NL | |
253 | Novo Nordisk Investigational Site | Torquay | United Kingdom | TQ2 7AA |
Sponsors and Collaborators
- Novo Nordisk A/S
Investigators
- Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- NN9535-3744
- 2012-002839-28
- U1111-1131-7227
Study Results
Participant Flow
Recruitment Details | The trial was conducted at 229 sites in 20 countries. Country (sites): Algeria (4), Argentina (7), Australia (8), Brazil (8), Bulgaria (5), Canada (13), Denmark (5), Germany (7), Israel (6), Italy (6), Malaysia (6), Mexico (9), Poland (5), Russia (11), Spain (6), Taiwan (4), Thailand (5), Turkey (10), United Kingdom (8) and United States (96). |
---|---|
Pre-assignment Detail | Subjects could be anti-glycaemic drug naïve, or treated with 1 or 2 oral anti diabetic drugs (OADs), or treated with human NPH insulin or long-acting insulin analogue or pre-mixed insulin, alone or in combination with 1 or 2 OAD(s). |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg |
---|---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Period Title: Overall Study | ||||
STARTED | 826 | 822 | 824 | 825 |
Premature Treatment Discontinuers | 164 | 186 | 151 | 159 |
COMPLETED | 812 | 811 | 804 | 805 |
NOT COMPLETED | 14 | 11 | 20 | 20 |
Baseline Characteristics
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg | Total |
---|---|---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Total of all reporting groups |
Overall Participants | 826 | 822 | 824 | 825 | 3297 |
Age, Customized (participants) [Number] | |||||
50-64 years |
440
53.3%
|
415
50.5%
|
419
50.8%
|
425
51.5%
|
1699
51.5%
|
65-74 years |
312
37.8%
|
324
39.4%
|
324
39.3%
|
317
38.4%
|
1277
38.7%
|
75-84 years |
71
8.6%
|
76
9.2%
|
75
9.1%
|
79
9.6%
|
301
9.1%
|
85 and over |
3
0.4%
|
7
0.9%
|
6
0.7%
|
4
0.5%
|
20
0.6%
|
Sex: Female, Male (Count of Participants) | |||||
Female |
331
40.1%
|
304
37%
|
342
41.5%
|
318
38.5%
|
1295
39.3%
|
Male |
495
59.9%
|
518
63%
|
482
58.5%
|
507
61.5%
|
2002
60.7%
|
Glycosylated haemoglobin (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [percentage of glycosylated haemoglobin] |
8.67
(1.39)
|
8.73
(1.51)
|
8.70
(1.49)
|
8.70
(1.45)
|
8.70
(1.46)
|
Fasting plasma glucose (mg/dL) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [mg/dL] |
185.4
(66.09)
|
182.9
(68.04)
|
185.8
(68.23)
|
184.6
(63.08)
|
184.7
(66.37)
|
Body weight (kg) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [kg] |
91.80
(20.25)
|
92.86
(21.05)
|
91.83
(20.35)
|
91.90
(20.75)
|
92.09
(20.60)
|
LDL-cholesterol (mg/dL) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [mg/dL] |
89.62
(39.08)
|
89.72
(34.49)
|
89.01
(38.35)
|
91.14
(37.90)
|
89.87
(37.49)
|
HDL-cholesterol (mg/dL) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [mg/dL] |
45.92
(13.00)
|
44.97
(12.42)
|
45.82
(12.92)
|
44.61
(12.26)
|
45.33
(12.66)
|
Systolic BP (mmHg) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [mmHg] |
136.1
(17.97)
|
135.8
(16.96)
|
135.8
(16.16)
|
134.8
(17.45)
|
135.6
(17.15)
|
Diastolic BP (mmHg) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [mmHg] |
77.10
(9.78)
|
76.88
(10.21)
|
77.54
(9.85)
|
76.66
(10.21)
|
77.05
(10.02)
|
Pulse rate (beats/min) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [beats/min] |
72.69
(11.22)
|
71.53
(10.86)
|
72.01
(10.62)
|
71.95
(10.92)
|
72.05
(10.91)
|
Total cholesterol (mg/dL) [Geometric Mean (Full Range) ] | |||||
Geometric Mean (Full Range) [mg/dL] |
165.38
|
164.96
|
164.38
|
165.97
|
165.17
|
Triglycerides (mg/dL) [Geometric Mean (Full Range) ] | |||||
Geometric Mean (Full Range) [mg/dL] |
163.66
|
158.93
|
162.30
|
163.00
|
161.96
|
Free fatty acids (mmol/L) [Geometric Mean (Full Range) ] | |||||
Geometric Mean (Full Range) [mmol/L] |
0.83
|
0.80
|
0.83
|
0.81
|
0.82
|
Outcome Measures
Title | Time From Randomisation to First Occurrence of a MACE, Defined as Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke |
---|---|
Description | Percentage of subjects experiencing a first event of a major adverse cardiovascular event (MACE), defined as cardiovascular (CV) death, non-fatal myocardial infarction (MI), or non-fatal stroke. |
Time Frame | Time from randomisation up to end of follow-up (scheduled at week 109) |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all the randomised subjects. As specified in the protocol, the two semaglutide dose arms (semaglutide 0.5 mg + semaglutide 1.0 mg) and the two placebo dose arms (placebo 0.5 mg + placebo 1.0 mg) were pooled for the analysis of this endpoint. |
Arm/Group Title | Semaglutide | Placebo |
---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 1648 | 1649 |
Number [percentage of subjects] |
6.6
|
8.9
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo |
---|---|---|
Comments | The primary endpoint was analysed using a stratified Cox proportional hazards model with treatment group (semaglutide, placebo) as fixed factor. Assuming the same population MACE risk for the semaglutide and placebo groups (i.e., the population hazards ratio [HR] equals 1), a total minimum of 122 events were needed in order to have at least 90% power to ascertain that the upper two-sided 95% confidence limit for the HR was less than 1.8. | |
Type of Statistical Test | Non-Inferiority or Equivalence | |
Comments | Non-inferiority of semaglutide versus placebo was considered to be confirmed if the upper limit of the two-sided 95% CI for the HR was below 1.8 or equivalent if the p-value for the one-sided test of: H0: HR ≥ 1.8 against Ha: HR <1.8 was less than 2.5% (or equivalent to 5% for a two-sided test). | |
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | The 'p-value' is for the two-sided Wald test of non-inferiority with limit 1.8. | |
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.74 | |
Confidence Interval |
(2-Sided) 95% 0.58 to 0.95 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide/Placebo |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo |
---|---|---|
Comments | A post hoc analysis of superiority of semaglutide versus placebo was performed based on the pre-specified Cox proportional hazard analysis using the two-sided Wald test of no difference, with treatment (semaglutide, placebo) as fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels). | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0167 |
Comments | The 'p-value' is for the two-sided Wald test of no difference. | |
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.74 | |
Confidence Interval |
(2-Sided) 95% 0.58 to 0.95 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide/Placebo |
Title | Time From Randomisation to First Occurrence of an Expanded Composite Cardiovascular Outcome |
---|---|
Description | Percentage of subjects experiencing first occurrence of an expanded composite CV outcome (defined as either MACE, revascularisation [coronary and peripheral], unstable angina requiring hospitalisation or hospitalisation for heart failure) |
Time Frame | Time from randomisation up to end of follow-up (scheduled at week 109) |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all the randomised subjects. As specified in the protocol, the two semaglutide dose arms (semaglutide 0.5 mg + semaglutide 1.0 mg) and the two placebo dose arms (placebo 0.5 mg + placebo 1.0 mg) were pooled for the analysis of this endpoint. |
Arm/Group Title | Semaglutide | Placebo |
---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 1648 | 1649 |
Number [percentage of subjects] |
12.1
|
16.0
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo |
---|---|---|
Comments | Analysis was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels). | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0016 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.74 | |
Confidence Interval |
(2-Sided) 95% 0.62 to 0.89 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide/Placebo |
Title | Time From Randomisation to Each Individual Component of the Expanded Composite Cardiovascular Outcome |
---|---|
Description | Percentage of subjects experiencing an event onset for each individual component of the expanded composite cardiovascular outcomes (defined as either MACE, revascularisation [coronary and peripheral], unstable angina requiring hospitalisation or hospitalisation for heart failure). |
Time Frame | Time from randomisation up to end of follow-up (scheduled at week 109) |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all the randomised subjects. As specified in the protocol, the two semaglutide dose arms (semaglutide 0.5 mg + semaglutide 1.0 mg) and the two placebo dose arms (placebo 0.5 mg + placebo 1.0 mg) were pooled for the analysis of this endpoint. |
Arm/Group Title | Semaglutide | Placebo |
---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 1648 | 1649 |
Cardiovascular death |
1.6
|
1.9
|
Non-fatal MI |
2.5
|
3.7
|
Non-fatal Stroke |
1.5
|
2.5
|
Revascularisation |
2.6
|
4.2
|
UAP requiring hospitalisation |
1.1
|
1.3
|
Hospitalisation for heart failure |
2.7
|
2.4
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo |
---|---|---|
Comments | Analysis for CV death was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels). | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.9181 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.98 | |
Confidence Interval |
(2-Sided) 95% 0.65 to 1.48 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide/Placebo |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo |
---|---|---|
Comments | Analysis for non-fatal myocardial infarction was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels). | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1194 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.74 | |
Confidence Interval |
(2-Sided) 95% 0.51 to 1.08 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide/Placebo |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo |
---|---|---|
Comments | Analysis for non-fatal stroke was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels). | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0438 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.61 | |
Confidence Interval |
(2-Sided) 95% 0.38 to 0.99 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide/Placebo |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo |
---|---|---|
Comments | Analysis for revascularisation was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels). | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0027 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.65 | |
Confidence Interval |
(2-Sided) 95% 0.50 to 0.86 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide/Placebo |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo |
---|---|---|
Comments | Analysis for 'unstable angina requiring hospitalisation' was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels). | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.4914 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.82 | |
Confidence Interval |
(2-Sided) 95% 0.47 to 1.44 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide/Placebo |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo |
---|---|---|
Comments | Analysis for hospitalisation for heart failure was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels). | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.5735 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.11 | |
Confidence Interval |
(2-Sided) 95% 0.77 to 1.61 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide/Placcbo |
Title | Time From Randomisation to First Occurrence of All-cause Death, Non-fatal MI, or Non-fatal Stroke |
---|---|
Description | Percentage of subjects experiencing a first occurrence of all-cause death, non-fatal MI, or non-fatal stroke. |
Time Frame | Time from randomisation up to end of follow-up (scheduled at week 109) |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all the randomised subjects. As specified in the protocol, the two semaglutide dose arms (semaglutide 0.5 mg + semaglutide 1.0 mg) and the two placebo dose arms (placebo 0.5 mg + placebo 1.0 mg) were pooled for the analysis of this endpoint. |
Arm/Group Title | Semaglutide | Placebo |
---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 1648 | 1649 |
Number [percentage of subjects] |
7.4
|
9.6
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo |
---|---|---|
Comments | Analysis for all-cause death, non-fatal MI or non-fatal stroke was done by Cox proportional hazards model with treatment (semaglutide; placebo) as a fixed factor and stratified by all possible combinations of the three stratification factors used in the randomisation procedure (in total 9 levels). | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0292 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.77 | |
Confidence Interval |
(2-Sided) 95% 0.61 to 0.97 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide/Placebo |
Title | Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Glycosylated Haemoglobin (HbA1c) |
---|---|
Description | Estimated mean change from baseline in glycosylated haemoglobin (HbA1c) to last assessment in the trial during the treatment period. |
Time Frame | Week 0, up to week 104 |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all the randomised subjects |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg |
---|---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 826 | 822 | 824 | 825 |
Least Squares Mean (Standard Error) [percentage of glycosylated haemoglobin] |
-1.09
(0.05)
|
-1.41
(0.05)
|
-0.44
(0.05)
|
-0.36
(0.05)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | -0.66 | |
Confidence Interval |
(2-Sided) 95% -0.80 to -0.52 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Sema 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | -1.05 | |
Confidence Interval |
(2-Sided) 95% -1.19 to -0.91 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Sema 1.0 mg - Placebo 1.0 mg |
Title | Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Fasting Plasma Glucose |
---|---|
Description | Estimated mean change from baseline to last assessment in fasting plasma glucose in the trial during the treatment period. |
Time Frame | Week 0, up to week 104 |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all the randomised subjects. |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg |
---|---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 826 | 822 | 824 | 825 |
Least Squares Mean (Standard Error) [mmol/L] |
-1.75
(0.12)
|
-2.11
(0.12)
|
-1.02
(0.12)
|
-0.88
(0.12)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | -0.72 | |
Confidence Interval |
(2-Sided) 95% -1.06 to -0.38 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Sema 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | -1.22 | |
Confidence Interval |
(2-Sided) 95% -1.56 to -0.88 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Sema 1.0 mg - Placebo 1.0 mg |
Title | Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Body Weight |
---|---|
Description | Estimated mean change from baseline to last assessment in body weight in the trial during the treatment period. |
Time Frame | Week 0, up to week 104 |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all the randomised subjects. As specified in the protocol, the two placebo dose arms (placebo 0.5 mg + placebo 1.0 mg) were pooled for the analysis of this endpoint. |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo |
---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg or 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment and the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 826 | 822 | 1649 |
Least Squares Mean (Standard Error) [kg] |
-3.57
(0.21)
|
-4.88
(0.22)
|
-0.62
(0.15)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | -2.95 | |
Confidence Interval |
(2-Sided) 95% -3.47 to -2.44 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Sema 0.5 mg - Placebo |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 0.5 mg |
---|---|---|
Comments | Analysis was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | -4.27 | |
Confidence Interval |
(2-Sided) 95% -4.78 to -3.75 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo |
Title | Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profile |
---|---|
Description | Estimated ratio to baseline at week 104 during the treatment period in lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides). |
Time Frame | Week 0, up to week 104 |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all randomised subjects. |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg |
---|---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 826 | 822 | 824 | 825 |
Total cholesterol (mg/dL) |
0.97
(0.01)
|
0.97
(0.01)
|
1.00
(0.01)
|
0.99
(0.01)
|
HDL-cholesterol (mg/dL) |
0.99
(0.01)
|
1.01
(0.01)
|
0.99
(0.01)
|
0.97
(0.01)
|
LDL-cholesterol (mg/dL) |
0.97
(0.01)
|
0.98
(0.01)
|
1.01
(0.01)
|
0.99
(0.01)
|
Triglycerides (mg/dL) |
0.93
(0.01)
|
0.92
(0.01)
|
0.96
(0.01)
|
0.98
(0.01)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for total cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. The response and its baseline value were log-transformed before analysis. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0149 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment ratio |
Estimated Value | 0.97 | |
Confidence Interval |
(2-Sided) 95% 0.95 to 1.00 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg/Placebo 0.5 mg |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for total cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. The response and its baseline value were log-transformed before analysis. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.2580 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment ratio |
Estimated Value | 0.99 | |
Confidence Interval |
(2-Sided) 95% 0.97 to 1.01 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg/Placebo 1.0 mg |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for HDL-cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.8106 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment ratio |
Estimated Value | 1.00 | |
Confidence Interval |
(2-Sided) 95% 0.99 to 1.02 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg/Placebo 0.5 mg |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for HDL-cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment ratio |
Estimated Value | 1.04 | |
Confidence Interval |
(2-Sided) 95% 1.02 to 1.06 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg/Placebo 1.0 mg |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for LDL-cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0185 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment ratio |
Estimated Value | 0.96 | |
Confidence Interval |
(2-Sided) 95% 0.93 to 0.99 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg/Placebo 0.5 mg |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for LDL-cholesterol was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.5996 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment ratio |
Estimated Value | 0.99 | |
Confidence Interval |
(2-Sided) 95% 0.96 to 1.03 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg/Placebo 1.0 mg |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for triglycerides was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1833 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment ratio |
Estimated Value | 0.97 | |
Confidence Interval |
(2-Sided) 95% 0.93 to 1.01 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg/Placebo 0.5 mg |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for triglycerides was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0009 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment ratio |
Estimated Value | 0.93 | |
Confidence Interval |
(2-Sided) 95% 0.89 to 0.97 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg/Placebo 1.0 mg |
Title | Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Urinary Albumin to Creatinine Ratio |
---|---|
Description | Estimated ratio to baseline in urinary albumin to creatinine ratio at week 104 during the treatment period. |
Time Frame | Week 0, up to week 104 |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all the randomised subjects |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg |
---|---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 826 | 822 | 824 | 825 |
Least Squares Mean (Standard Error) [mg/g] |
1.02
(0.05)
|
0.91
(0.05)
|
1.32
(0.07)
|
1.29
(0.06)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for urinary albumin to creatinine ration was donne using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. The response and its baseline value were log-transformed before analysis. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0003 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment ratio |
Estimated Value | 0.78 | |
Confidence Interval |
(2-Sided) 95% 0.68 to 0.89 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Sema 0.5 mg / Placebo 0.5 mg |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for urinary albumin to creatinine ration was donne using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment ratio |
Estimated Value | 0.71 | |
Confidence Interval |
(2-Sided) 95% 0.62 to 0.81 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Sema 1.0 mg / Placebo 1.0 mg |
Title | Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital Signs |
---|---|
Description | Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (diastolic blood pressure and systolic blood pressure). |
Time Frame | Week 0, up to week 104 |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all the randomised subjects. |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg |
---|---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 826 | 822 | 824 | 825 |
Diastolic blood pressure (mmHg) |
-1.37
(0.32)
|
-1.57
(0.32)
|
-1.42
(0.32)
|
-1.71
(0.32)
|
Systolic blood pressure (mmHg) |
-3.44
(0.54)
|
-5.37
(0.54)
|
-2.17
(0.54)
|
-2.78
(0.54)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for diastolic blood pressure was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.9205 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 0.04 | |
Confidence Interval |
(2-Sided) 95% -0.83 to 0.92 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for diastolic blood pressure was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.7477 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 0.14 | |
Confidence Interval |
(2-Sided) 95% -0.74 to 1.03 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for systolic blood pressure was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0976 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | -1.27 | |
Confidence Interval |
(2-Sided) 95% -2.77 to 0.23 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for systolic blood pressure was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0008 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | -2.59 | |
Confidence Interval |
(2-Sided) 95% -4.09 to -1.08 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Title | Incidence During the Trial in Other Treatment Outcomes: Hypoglycaemic Events |
---|---|
Description | Rates (event rate per 100 exposure years) of severe or blood glucose confirmed symptomatic hypoglycaemia defned as an episode that was severe according to the American diabetic association (ADA) classification or blood glucose (BG) confirmed by a PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. |
Time Frame | Week 0 - 109 |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all randomised subjects. |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg |
---|---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 826 | 822 | 824 | 825 |
Number [Event rate per 100 exposure years] |
37.5
|
36.2
|
35.3
|
39.7
|
Title | Incidence During the Trial in Other Treatment Outcomes: Adverse Events |
---|---|
Description | Rates (event rate per 100 years of exposure) of treatment emergent adverse events. |
Time Frame | Weeks 0-109 |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all randomised subjects. |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg |
---|---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 826 | 822 | 824 | 825 |
Number [Event rate per 100 years of exposure] |
330.5
|
337.0
|
317.4
|
298.3
|
Title | Occurrence During the Trial in Other Treatment Outcomes: Anti-semaglutide Antibodies |
---|---|
Description | The percentage of subjects that tested positive for anti-semaglutide antibodies at any time point post-baseline during the trial, from week 0 to week 109. |
Time Frame | Weeks 0-109 |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all randomised subjects |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg |
---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 826 | 822 |
Number [Percentage of subjects] |
1.4
|
2.3
|
Title | Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Patient Reported Outcome (PRO) |
---|---|
Description | Estimated mean change from baseline to last assessment in the trial in patient reported outcomes (PRO). PRO questionnaire (SF-36v2TM) measured the individual overall health related quality of life namely bodily pain, general health, mental component summary, mental health, physical component summary, physical functioning, role-emotional, role-physical, social functioning and vitality. The PRO scores were transformed to a 0-100 scale with higher scores indicating greater health related quality of life. |
Time Frame | Week 0, up to week 104 |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all randomised subjects. |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg |
---|---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 826 | 822 | 824 | 825 |
Bodily pain |
0.66
(0.35)
|
1.82
(0.35)
|
0.16
(0.35)
|
0.35
(0.35)
|
General health |
1.66
(0.29)
|
2.55
(0.29)
|
0.78
(0.29)
|
1.13
(0.30)
|
Mental component summary |
0.0
(0.35)
|
0.86
(0.35)
|
-0.17
(0.35)
|
-0.11
(0.35)
|
Mental health |
0.48
(0.33)
|
1.08
(0.33)
|
-0.14
(0.33)
|
-0.31
(0.33)
|
Physical component summary |
0.76
(0.28)
|
1.74
(0.28)
|
0.07
(0.28)
|
0.35
(0.28)
|
Physical functioning |
0.42
(0.32)
|
1.12
(0.32)
|
-0.38
(0.32)
|
-0.37
(0.33)
|
Role-emotional |
0.17
(0.42)
|
0.89
(0.42)
|
-0.36
(0.42)
|
-0.05
(0.42)
|
Role-physical |
0.39
(0.34)
|
1.18
(0.35)
|
-0.33
(0.35)
|
0.03
(0.35)
|
Social functioning |
-0.25
(0.35)
|
0.97
(0.35)
|
-0.20
(0.36)
|
-0.17
(0.36)
|
Vitality |
0.29
(0.31)
|
1.55
(0.31)
|
-0.04
(0.31)
|
0.35
(0.31)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for bodily pain was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3171 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 0.50 | |
Confidence Interval |
(2-Sided) 95% -0.48 to 1.47 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for bodily pain was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0031 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 1.47 | |
Confidence Interval |
(2-Sided) 95% 0.50 to 2.45 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for general health was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0350 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 0.87 | |
Confidence Interval |
(2-Sided) 95% 0.06 to 1.69 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for general health was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0007 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 1.42 | |
Confidence Interval |
(2-Sided) 95% 0.60 to 2.24 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for mental component summary was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.7277 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 0.17 | |
Confidence Interval |
(2-Sided) 95% -0.79 to 1.13 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for mental component summary was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0489 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 0.97 | |
Confidence Interval |
(2-Sided) 95% 0.00 to 1.94 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for mental health was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1860 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment Difference |
Estimated Value | 0.61 | |
Confidence Interval |
(2-Sided) 95% -0.30 to 1.53 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for mental health was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0029 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 1.39 | |
Confidence Interval |
(2-Sided) 95% 0.48 to 2.31 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Statistical Analysis 9
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for physical component summary was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0833 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 0.68 | |
Confidence Interval |
(2-Sided) 95% -0.09 to 1.45 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 10
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for physical component summary was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0004 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 1.40 | |
Confidence Interval |
(2-Sided) 95% 0.62 to 2.17 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Statistical Analysis 11
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for physical functioning was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0799 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 0.80 | |
Confidence Interval |
(2-Sided) 95% -0.10 to 1.69 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 12
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for physical functioning was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0011 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 1.50 | |
Confidence Interval |
(2-Sided) 95% 0.60 to 2.40 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Statistical Analysis 13
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for role emotional was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.3717 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 0.53 | |
Confidence Interval |
(2-Sided) 95% -0.63 to 1.68 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 14
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for role emotional was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1136 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 0.94 | |
Confidence Interval |
(2-Sided) 95% -0.22 to 2.10 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Statistical Analysis 15
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for role physical was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.1431 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 0.72 | |
Confidence Interval |
(2-Sided) 95% -0.24 to 1.67 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 16
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for role physical was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0197 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 1.14 | |
Confidence Interval |
(2-Sided) 95% 0.18 to 2.11 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Statistical Analysis 17
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for social functioning was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.9223 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | -0.05 | |
Confidence Interval |
(2-Sided) 95% -1.03 to 0.93 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 18
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for social functioning was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0237 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 1.14 | |
Confidence Interval |
(2-Sided) 95% 0.15 to 2.13 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Statistical Analysis 19
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for vitality was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.4523 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 0.33 | |
Confidence Interval |
(2-Sided) 95% -0.53 to 1.19 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 20
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for vitality was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0064 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 1.20 | |
Confidence Interval |
(2-Sided) 95% 0.34 to 2.07 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Title | Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profile (Free Fatty Acids) |
---|---|
Description | Estimated ratio to baseline at week 104 during the treatment period in lipid profile (free fatty acids). |
Time Frame | Week 0, up to week 104 |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all randomised subjects. |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg |
---|---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 826 | 822 | 824 | 825 |
Least Squares Mean (Standard Error) [mmol/L] |
0.95
(0.02)
|
0.91
(0.01)
|
0.96
(0.02)
|
0.99
(0.02)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for free fatty acids was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.7796 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment ratio |
Estimated Value | 0.99 | |
Confidence Interval |
(2-Sided) 95% 0.95 to 1.04 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg/Placebo 0.5 mg |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for free fatty acids was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0003 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment ratio |
Estimated Value | 0.92 | |
Confidence Interval |
(2-Sided) 95% 0.88 to 0.96 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg/Placebo 1.0 mg |
Title | Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital Signs (Pulse Rate) |
---|---|
Description | Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (pulse rate). |
Time Frame | Week 0, up to week 104 |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set included all the randomised subjects. |
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg |
---|---|---|---|---|
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. |
Measure Participants | 826 | 822 | 824 | 825 |
Least Squares Mean (Standard Error) [beats/min] |
2.12
(0.34)
|
2.41
(0.34)
|
0.09
(0.34)
|
-0.07
(0.34)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Semaglutide, Placebo 0.5 mg |
---|---|---|
Comments | Analysis for pulse rate was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 2.02 | |
Confidence Interval |
(2-Sided) 95% 1.07 to 2.98 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 0.5 mg - Placebo 0.5 mg |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Placebo 1.0 mg |
---|---|---|
Comments | Analysis for pulse rate was done using a mixed model for repeated measurements with treatment (4 levels) and stratification (9 levels) as fixed factors and baseline value as covariate, all nested within visit. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | ||
Method of Estimation | Estimation Parameter | Treatment difference |
Estimated Value | 2.47 | |
Confidence Interval |
(2-Sided) 95% 1.52 to 3.43 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Semaglutide 1.0 mg - Placebo 1.0 mg |
Adverse Events
Time Frame | Adverse events from the first trial-related activity after the subject had signed the informed consent (week -2) until the end of the posttreatment follow-up period (week 109). | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | Safety was assessed using the full analysis set which included all randomised subjects. Subjects contributed to the evaluation as randomised. | |||||||
Arm/Group Title | Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg | ||||
Arm/Group Description | Subjects received once-weekly dose of semaglutide 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of semaglutide 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Semaglutide was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 0.5 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 0.5 mg was achieved after 4 weeks of treatment. Each subject was treated for 104 weeks. | Subjects received once-weekly dose of placebo 1.0 mg as an add-on to their standard-of-care treatment. Injections were administered subcutaneously in the thigh, abdomen or upper arm, at any time of day irrespective of meals. The injections were to be administered on the same weekday during the trial. Placebo was initiated at a dose of 0.25 mg and was escalated (doubled) to 0.5 mg after 4 weeks. Hence the target dose of 1.0 mg was achieved after 8 weeks of treatment. Each subject was treated for 104 weeks. | ||||
All Cause Mortality |
||||||||
Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 289/826 (35%) | 276/822 (33.6%) | 329/824 (39.9%) | 298/825 (36.1%) | ||||
Blood and lymphatic system disorders | ||||||||
Anaemia | 5/826 (0.6%) | 5 | 4/822 (0.5%) | 4 | 2/824 (0.2%) | 2 | 2/825 (0.2%) | 2 |
Haemorrhagic anaemia | 1/826 (0.1%) | 1 | 2/822 (0.2%) | 2 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Iron deficiency anaemia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Leukocytosis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Lymphadenopathy | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Lymphadenopathy mediastinal | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Microcytic anaemia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Splenic vein thrombosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Splenomegaly | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Thrombocytopenia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Cardiac disorders | ||||||||
Acute coronary syndrome | 4/826 (0.5%) | 4 | 3/822 (0.4%) | 3 | 1/824 (0.1%) | 1 | 2/825 (0.2%) | 2 |
Acute left ventricular failure | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Acute myocardial infarction | 16/826 (1.9%) | 21 | 13/822 (1.6%) | 14 | 15/824 (1.8%) | 15 | 27/825 (3.3%) | 28 |
Angina pectoris | 9/826 (1.1%) | 9 | 9/822 (1.1%) | 10 | 16/824 (1.9%) | 17 | 12/825 (1.5%) | 12 |
Angina unstable | 13/826 (1.6%) | 16 | 15/822 (1.8%) | 18 | 19/824 (2.3%) | 21 | 22/825 (2.7%) | 23 |
Aortic valve disease | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Aortic valve stenosis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Arrhythmia | 1/826 (0.1%) | 2 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 3/825 (0.4%) | 3 |
Arteriosclerosis coronary artery | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 3/825 (0.4%) | 3 |
Atrial fibrillation | 14/826 (1.7%) | 16 | 12/822 (1.5%) | 15 | 20/824 (2.4%) | 22 | 18/825 (2.2%) | 19 |
Atrial flutter | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 4/824 (0.5%) | 4 | 1/825 (0.1%) | 1 |
Atrioventricular block | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Atrioventricular block complete | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 3/825 (0.4%) | 3 |
Atrioventricular block first degree | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Atrioventricular block second degree | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Bradycardia | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 2 | 2/825 (0.2%) | 2 |
Bundle branch block left | 2/826 (0.2%) | 2 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 3/825 (0.4%) | 3 |
Bundle branch block right | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cardiac arrest | 5/826 (0.6%) | 6 | 2/822 (0.2%) | 2 | 3/824 (0.4%) | 3 | 2/825 (0.2%) | 3 |
Cardiac asthma | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cardiac failure | 10/826 (1.2%) | 11 | 10/822 (1.2%) | 10 | 7/824 (0.8%) | 9 | 3/825 (0.4%) | 4 |
Cardiac failure acute | 2/826 (0.2%) | 2 | 0/822 (0%) | 0 | 4/824 (0.5%) | 4 | 1/825 (0.1%) | 2 |
Cardiac failure chronic | 8/826 (1%) | 8 | 4/822 (0.5%) | 4 | 6/824 (0.7%) | 6 | 3/825 (0.4%) | 3 |
Cardiac failure congestive | 21/826 (2.5%) | 31 | 14/822 (1.7%) | 17 | 15/824 (1.8%) | 19 | 18/825 (2.2%) | 21 |
Cardiac tamponade | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cardiac ventricular thrombosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Cardio-respiratory arrest | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cardiogenic shock | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 3/824 (0.4%) | 3 | 1/825 (0.1%) | 1 |
Cardiomyopathy | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cardiopulmonary failure | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Cardiovascular insufficiency | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Congestive cardiomyopathy | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Coronary artery disease | 11/826 (1.3%) | 11 | 9/822 (1.1%) | 9 | 5/824 (0.6%) | 6 | 2/825 (0.2%) | 3 |
Coronary artery insufficiency | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Coronary artery occlusion | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Coronary artery stenosis | 7/826 (0.8%) | 7 | 2/822 (0.2%) | 2 | 4/824 (0.5%) | 4 | 1/825 (0.1%) | 1 |
Diabetic cardiomyopathy | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Hypertensive cardiomyopathy | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Ischaemic cardiomyopathy | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Left ventricular failure | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Mitral valve incompetence | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Myocardial infarction | 4/826 (0.5%) | 4 | 10/822 (1.2%) | 10 | 9/824 (1.1%) | 10 | 12/825 (1.5%) | 14 |
Myocardial ischaemia | 6/826 (0.7%) | 6 | 2/822 (0.2%) | 2 | 3/824 (0.4%) | 3 | 2/825 (0.2%) | 2 |
Myocarditis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Nodal arrhythmia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Pericardial effusion | 2/826 (0.2%) | 2 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Right ventricular failure | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Silent myocardial infarction | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Sinus bradycardia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Sinus node dysfunction | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 2/824 (0.2%) | 2 | 0/825 (0%) | 0 |
Supraventricular extrasystoles | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Supraventricular tachycardia | 2/826 (0.2%) | 2 | 2/822 (0.2%) | 2 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Tachycardia | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Tricuspid valve incompetence | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Ventricular arrhythmia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Ventricular asystole | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Ventricular extrasystoles | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Ventricular fibrillation | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 1/824 (0.1%) | 1 | 2/825 (0.2%) | 2 |
Ventricular hypokinesia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Ventricular tachyarrhythmia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Ventricular tachycardia | 1/826 (0.1%) | 1 | 8/822 (1%) | 8 | 1/824 (0.1%) | 2 | 2/825 (0.2%) | 2 |
Atrial thrombosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Bradyarrhythmia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 0/825 (0%) | 0 |
Cor pulmonale acute | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Pulmonary valve stenosis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Stress cardiomyopathy | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Congenital, familial and genetic disorders | ||||||||
Phimosis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Ear and labyrinth disorders | ||||||||
Deafness neurosensory | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Otosclerosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Tympanic membrane perforation | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Vertigo | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Endocrine disorders | ||||||||
Goitre | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 2/825 (0.2%) | 2 |
Hyperthyroidism | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Inappropriate antidiuretic hormone secretion | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Thyroid mass | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Eye disorders | ||||||||
Blindness | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Cataract | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 5/825 (0.6%) | 6 |
Cataract cortical | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Cataract nuclear | 1/826 (0.1%) | 2 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cystoid macular oedema | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Diabetic retinopathy | 4/826 (0.5%) | 4 | 2/822 (0.2%) | 3 | 2/824 (0.2%) | 2 | 4/825 (0.5%) | 4 |
Diplopia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Eyelid dermatochalasis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Eyelid ptosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Glaucoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Iridocyclitis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Macular fibrosis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Macular oedema | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Open angle glaucoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Optic ischaemic neuropathy | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Retinal artery occlusion | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Retinal degeneration | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Retinal detachment | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 2/825 (0.2%) | 2 |
Retinopathy haemorrhagic | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Vitreous haemorrhage | 2/826 (0.2%) | 2 | 2/822 (0.2%) | 2 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Amaurosis fugax | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Gastrointestinal disorders | ||||||||
Abdominal mass | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Abdominal pain | 2/826 (0.2%) | 2 | 6/822 (0.7%) | 6 | 2/824 (0.2%) | 3 | 2/825 (0.2%) | 2 |
Abdominal pain lower | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Abdominal pain upper | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Ascites | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Change of bowel habit | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Chronic gastritis | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Colitis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Colitis ischaemic | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Colitis ulcerative | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Constipation | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Diarrhoea | 2/826 (0.2%) | 2 | 6/822 (0.7%) | 6 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Diverticulum | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Diverticulum intestinal | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Duodenal ulcer | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Duodenal ulcer haemorrhage | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Duodenitis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Enterocolitis haemorrhagic | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Epigastric discomfort | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Faeces discoloured | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Gastric disorder | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Gastric ileus | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Gastric polyps | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Gastric ulcer | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Gastric ulcer haemorrhage | 2/826 (0.2%) | 2 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Gastritis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Gastritis haemorrhagic | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Gastroduodenitis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Gastrointestinal haemorrhage | 5/826 (0.6%) | 5 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 4/825 (0.5%) | 4 |
Gastrointestinal ischaemia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Gastrooesophageal reflux disease | 3/826 (0.4%) | 3 | 3/822 (0.4%) | 3 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Hiatus hernia | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 2 | 0/825 (0%) | 0 |
Impaired gastric emptying | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Inguinal hernia | 4/826 (0.5%) | 4 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Intestinal haemorrhage | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Intestinal ischaemia | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Intestinal obstruction | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Large intestinal haemorrhage | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Large intestine polyp | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Lower gastrointestinal haemorrhage | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Melaena | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Mouth ulceration | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Nausea | 0/826 (0%) | 0 | 3/822 (0.4%) | 3 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Pancreatic cyst | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Pancreatitis | 2/826 (0.2%) | 2 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 4/825 (0.5%) | 4 |
Pancreatitis acute | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 2/825 (0.2%) | 2 |
Peptic ulcer | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Peritoneal haemorrhage | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Proctitis haemorrhagic | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Rectal prolapse | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Small intestinal obstruction | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 2/825 (0.2%) | 2 |
Umbilical hernia | 2/826 (0.2%) | 2 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 2/825 (0.2%) | 2 |
Upper gastrointestinal haemorrhage | 2/826 (0.2%) | 2 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Volvulus of small bowel | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Vomiting | 0/826 (0%) | 0 | 3/822 (0.4%) | 3 | 2/824 (0.2%) | 2 | 2/825 (0.2%) | 2 |
Diaphragmatic hernia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Haematemesis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Intestinal perforation | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Oesophageal spasm | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Pneumoperitoneum | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
General disorders | ||||||||
Asthenia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 2/825 (0.2%) | 2 |
Chest discomfort | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Chest pain | 1/826 (0.1%) | 1 | 3/822 (0.4%) | 3 | 5/824 (0.6%) | 6 | 3/825 (0.4%) | 3 |
Death | 2/826 (0.2%) | 2 | 3/822 (0.4%) | 3 | 3/824 (0.4%) | 3 | 2/825 (0.2%) | 2 |
Device malfunction | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Gait disturbance | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 2/825 (0.2%) | 2 |
Generalised oedema | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hyperthermia malignant | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Impaired healing | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Metaplasia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Microlithiasis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Multi-organ failure | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 2/825 (0.2%) | 2 |
Necrosis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Non-cardiac chest pain | 8/826 (1%) | 8 | 5/822 (0.6%) | 5 | 8/824 (1%) | 8 | 4/825 (0.5%) | 5 |
Oedema peripheral | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Pyrexia | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 2 | 0/825 (0%) | 0 |
Sudden cardiac death | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Sudden death | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Drug intolerance | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Oedema | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hepatobiliary disorders | ||||||||
Bile duct stone | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Biliary colic | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Cholangitis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cholecystitis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 4/824 (0.5%) | 4 | 2/825 (0.2%) | 2 |
Cholecystitis acute | 3/826 (0.4%) | 3 | 0/822 (0%) | 0 | 6/824 (0.7%) | 6 | 2/825 (0.2%) | 2 |
Cholecystitis chronic | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Cholelithiasis | 4/826 (0.5%) | 4 | 2/822 (0.2%) | 2 | 4/824 (0.5%) | 4 | 1/825 (0.1%) | 1 |
Cholelithiasis obstructive | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cholestasis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Gallbladder necrosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Gallbladder polyp | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Hepatic cirrhosis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Hepatic congestion | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Hydrocholecystis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Ischaemic hepatitis | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Jaundice | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hepatic failure | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Pneumobilia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Immune system disorders | ||||||||
Anaphylactic shock | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Drug hypersensitivity | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Hypersensitivity | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Sarcoidosis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Infections and infestations | ||||||||
Abscess | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Abscess limb | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Acute hepatitis B | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Appendicitis | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 2/825 (0.2%) | 2 |
Bacteraemia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Boutonneuse fever | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Bronchitis | 2/826 (0.2%) | 2 | 2/822 (0.2%) | 2 | 4/824 (0.5%) | 4 | 2/825 (0.2%) | 2 |
Bronchopneumonia | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Campylobacter gastroenteritis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Campylobacter infection | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cellulitis | 6/826 (0.7%) | 6 | 3/822 (0.4%) | 3 | 7/824 (0.8%) | 7 | 9/825 (1.1%) | 10 |
Clostridium difficile colitis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Cystitis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 2/825 (0.2%) | 2 |
Dengue fever | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Device related sepsis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Diabetic foot infection | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Diverticulitis | 1/826 (0.1%) | 1 | 2/822 (0.2%) | 2 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Endocarditis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Enteritis infectious | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Enterococcal infection | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Epididymitis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Escherichia infection | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Escherichia sepsis | 1/826 (0.1%) | 1 | 2/822 (0.2%) | 2 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Gangrene | 2/826 (0.2%) | 2 | 1/822 (0.1%) | 1 | 4/824 (0.5%) | 4 | 2/825 (0.2%) | 2 |
Gastroenteritis | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 4/824 (0.5%) | 4 | 2/825 (0.2%) | 2 |
Gastroenteritis rotavirus | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 2 | 0/825 (0%) | 0 |
Gastroenteritis salmonella | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Gastroenteritis viral | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Herpes zoster | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Implant site infection | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Incision site infection | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Infected skin ulcer | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Infectious colitis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Infective exacerbation of chronic obstructive airways disease | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Influenza | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 2 | 2/825 (0.2%) | 2 |
Labyrinthitis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Liver abscess | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Lobar pneumonia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Localised infection | 1/826 (0.1%) | 1 | 2/822 (0.2%) | 2 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 2 |
Lower respiratory tract infection | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Meningitis bacterial | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Necrotising fasciitis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Oesophageal candidiasis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Osteomyelitis | 5/826 (0.6%) | 5 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 2 | 3/825 (0.4%) | 3 |
Otitis externa | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Paronychia | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Perirectal abscess | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Peritonitis | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Peritonsillar abscess | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Periumbilical abscess | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Pharyngitis | 1/826 (0.1%) | 1 | 2/822 (0.2%) | 2 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Pneumonia | 18/826 (2.2%) | 19 | 15/822 (1.8%) | 16 | 22/824 (2.7%) | 26 | 14/825 (1.7%) | 14 |
Pneumonia pneumococcal | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Post procedural infection | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Post procedural pneumonia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Postoperative wound infection | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 2/825 (0.2%) | 2 |
Pseudomembranous colitis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Pulmonary sepsis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Pyelonephritis | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Pyelonephritis acute | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Pyelonephritis chronic | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Respiratory tract infection viral | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Sepsis | 7/826 (0.8%) | 7 | 4/822 (0.5%) | 4 | 3/824 (0.4%) | 3 | 7/825 (0.8%) | 7 |
Septic shock | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 4/824 (0.5%) | 4 | 3/825 (0.4%) | 3 |
Sinusitis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 2 |
Soft tissue infection | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Splenic abscess | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Staphylococcal infection | 2/826 (0.2%) | 2 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Staphylococcal osteomyelitis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Staphylococcal sepsis | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Subcutaneous abscess | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Tooth abscess | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Tuberculosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Upper respiratory tract infection | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 0/825 (0%) | 0 |
Urinary tract infection | 9/826 (1.1%) | 9 | 2/822 (0.2%) | 2 | 10/824 (1.2%) | 10 | 6/825 (0.7%) | 6 |
Urinary tract infection pseudomonal | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Urinary tract infection staphylococcal | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Urosepsis | 2/826 (0.2%) | 2 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Vestibular neuronitis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Viral infection | 2/826 (0.2%) | 2 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Abdominal sepsis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Aspergilloma | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Bronchitis bacterial | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Gastritis viral | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Groin abscess | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Laryngitis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Pneumonia respiratory syncytial viral | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Respiratory tract infection | 1/826 (0.1%) | 2 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Septic encephalopathy | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Staphylococcal bacteraemia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Wound infection bacterial | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||
Accident at work | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Anaemia postoperative | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Animal bite | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Ankle fracture | 2/826 (0.2%) | 2 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 0/825 (0%) | 0 |
Contusion | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Dural tear | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Failure to anastomose | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Fall | 11/826 (1.3%) | 11 | 5/822 (0.6%) | 5 | 11/824 (1.3%) | 11 | 8/825 (1%) | 8 |
Femur fracture | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Foot fracture | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Hand fracture | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Head injury | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Humerus fracture | 0/826 (0%) | 0 | 2/822 (0.2%) | 3 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Incorrect dose administered | 1/826 (0.1%) | 2 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Injury | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Intentional overdose | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Laceration | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Limb injury | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Meniscus injury | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Muscle strain | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Overdose | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Post procedural haematoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Postoperative ileus | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Postoperative respiratory failure | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Radius fracture | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Rib fracture | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Road traffic accident | 2/826 (0.2%) | 2 | 4/822 (0.5%) | 4 | 3/824 (0.4%) | 3 | 4/825 (0.5%) | 5 |
Scapula fracture | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Seroma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Skin abrasion | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Skull fracture | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Spinal compression fracture | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Subdural haematoma | 1/826 (0.1%) | 1 | 2/822 (0.2%) | 2 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Tendon rupture | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Thermal burn | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Toxicity to various agents | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 2 | 1/825 (0.1%) | 1 |
Traumatic fracture | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Traumatic haemothorax | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Traumatic ulcer | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Vascular graft complication | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Vascular graft occlusion | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Vascular pseudoaneurysm | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Wound | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Wound necrosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Wrong drug administered | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Alcohol poisoning | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Burns third degree | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cervical vertebral fracture | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Hip fracture | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Incisional hernia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Lumbar vertebral fracture | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Near drowning | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Investigations | ||||||||
Amylase increased | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Arteriogram coronary | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Bacterial test positive | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Blood alkaline phosphatase increased | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Blood bilirubin increased | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Blood creatinine increased | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Blood glucose fluctuation | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Blood glucose increased | 1/826 (0.1%) | 6 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Blood urea increased | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Catheterisation cardiac | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Ejection fraction decreased | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Electrocardiogram QT prolonged | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Electrocardiogram ST segment abnormal | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Electrocardiogram T wave inversion | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Electrocardiogram change | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Lipase increased | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Liver function test abnormal | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Pancreatic enzymes increased | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Transaminases increased | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Troponin increased | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 2/825 (0.2%) | 2 |
Weight decreased | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Coagulation time prolonged | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||
Acidosis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Dehydration | 3/826 (0.4%) | 3 | 5/822 (0.6%) | 5 | 2/824 (0.2%) | 2 | 0/825 (0%) | 0 |
Diabetes mellitus | 2/826 (0.2%) | 2 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Diabetes mellitus inadequate control | 4/826 (0.5%) | 4 | 1/822 (0.1%) | 1 | 5/824 (0.6%) | 7 | 4/825 (0.5%) | 5 |
Diabetic ketoacidosis | 1/826 (0.1%) | 2 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Electrolyte imbalance | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Failure to thrive | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Fluid overload | 2/826 (0.2%) | 2 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 2 | 0/825 (0%) | 0 |
Gout | 1/826 (0.1%) | 2 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 2/825 (0.2%) | 2 |
Hyperglycaemia | 3/826 (0.4%) | 3 | 2/822 (0.2%) | 2 | 4/824 (0.5%) | 4 | 4/825 (0.5%) | 4 |
Hyperkalaemia | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 3/824 (0.4%) | 4 | 1/825 (0.1%) | 1 |
Hypocalcaemia | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hypoglycaemia | 7/826 (0.8%) | 8 | 2/822 (0.2%) | 2 | 5/824 (0.6%) | 7 | 6/825 (0.7%) | 6 |
Hypokalaemia | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Hypomagnesaemia | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hyponatraemia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 4/824 (0.5%) | 4 | 0/825 (0%) | 0 |
Hypovolaemia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Lactic acidosis | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Obesity | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Metabolic acidosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Metabolic disorder | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||
Arthralgia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Arthritis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 2/825 (0.2%) | 2 |
Back pain | 1/826 (0.1%) | 1 | 4/822 (0.5%) | 4 | 1/824 (0.1%) | 1 | 6/825 (0.7%) | 6 |
Chondrolysis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Costochondritis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Diabetic arthropathy | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Fibromyalgia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Foot deformity | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Intervertebral disc disorder | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Intervertebral disc protrusion | 3/826 (0.4%) | 3 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Lumbar spinal stenosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Muscle spasms | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Musculoskeletal chest pain | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 4/824 (0.5%) | 5 | 3/825 (0.4%) | 3 |
Musculoskeletal pain | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Neck pain | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Osteoarthritis | 6/826 (0.7%) | 7 | 8/822 (1%) | 8 | 9/824 (1.1%) | 9 | 10/825 (1.2%) | 10 |
Osteonecrosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Pain in extremity | 1/826 (0.1%) | 2 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Rheumatoid arthritis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Spinal column stenosis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 4 | 0/825 (0%) | 0 |
Spinal osteoarthritis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Synovial cyst | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Flank pain | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Mobility decreased | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Muscular weakness | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Soft tissue disorder | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
Acute lymphocytic leukaemia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Acute myeloid leukaemia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Adenocarcinoma gastric | 2/826 (0.2%) | 2 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Adenocarcinoma of colon | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Adenocarcinoma pancreas | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Anaplastic astrocytoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
B-cell lymphoma | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 2/825 (0.2%) | 2 |
B-cell small lymphocytic lymphoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Basal cell carcinoma | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Benign lymph node neoplasm | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Benign neoplasm of thyroid gland | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Bladder neoplasm | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Bladder papilloma | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Bladder transitional cell carcinoma | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Bladder transitional cell carcinoma recurrent | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Bladder transitional cell carcinoma stage II | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Bone cancer metastatic | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Breast cancer | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Breast cancer in situ | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Breast cancer stage III | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Bronchial carcinoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Cholangiocarcinoma | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 2 | 0/825 (0%) | 0 |
Cholesteatoma | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Choroid melanoma | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Chronic lymphocytic leukaemia | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Clear cell renal cell carcinoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Colon adenoma | 0/826 (0%) | 0 | 4/822 (0.5%) | 4 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Colon cancer | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Colon cancer metastatic | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Colon neoplasm | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Colorectal cancer | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Endometrial adenocarcinoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Endometrial sarcoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Extranodal marginal zone B-cell lymphoma (MALT type) | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Gallbladder adenocarcinoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Gastric cancer | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Glomus tumour | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Growth hormone-producing pituitary tumour | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Hepatic adenoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Hepatic cancer | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Invasive ductal breast carcinoma | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Laryngeal squamous cell carcinoma | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Lip neoplasm malignant stage unspecified | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Lung adenocarcinoma | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Lung adenocarcinoma stage IV | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Lung carcinoma cell type unspecified stage IV | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Lung neoplasm | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Lung neoplasm malignant | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Malignant melanoma | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Metastases to central nervous system | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Metastases to liver | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Metastases to lung | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Metastases to lymph nodes | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Metastatic gastric cancer | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Neoplasm of appendix | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Non-small cell lung cancer | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Ovarian epithelial cancer | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Ovarian germ cell teratoma benign | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Pancreatic carcinoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Pancreatic carcinoma metastatic | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Papillary thyroid cancer | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Paraganglion neoplasm | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Parathyroid tumour benign | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 2 | 2/825 (0.2%) | 2 |
Phaeochromocytoma | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Plasma cell myeloma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Prostate cancer | 3/826 (0.4%) | 3 | 3/822 (0.4%) | 3 | 4/824 (0.5%) | 4 | 1/825 (0.1%) | 1 |
Prostate cancer metastatic | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Prostate cancer recurrent | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Prostate cancer stage I | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Prostate cancer stage III | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Rectal cancer | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Renal cancer metastatic | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Renal cancer stage I | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Renal cell carcinoma | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Small cell lung cancer | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 2/824 (0.2%) | 2 | 0/825 (0%) | 0 |
Squamous cell carcinoma | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Squamous cell carcinoma of lung | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Squamous cell carcinoma of skin | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Thyroid neoplasm | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Transitional cell carcinoma | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Ureteric cancer | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Uterine leiomyoma | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Brain neoplasm | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Chondroma | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Invasive breast carcinoma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Lung adenocarcinoma stage 0 | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Metastases to bone | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Pancreatic carcinoma stage IV | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Thyroid cancer metastatic | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Nervous system disorders | ||||||||
Brain oedema | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Brain stem infarction | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Carotid artery stenosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 3/824 (0.4%) | 3 | 3/825 (0.4%) | 3 |
Cerebellar haemorrhage | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Cerebellar syndrome | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Cerebral haemorrhage | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cerebral infarction | 2/826 (0.2%) | 2 | 2/822 (0.2%) | 3 | 3/824 (0.4%) | 3 | 0/825 (0%) | 0 |
Cerebral ischaemia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Cerebrospinal fluid leakage | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Cerebrovascular accident | 3/826 (0.4%) | 3 | 3/822 (0.4%) | 3 | 6/824 (0.7%) | 6 | 6/825 (0.7%) | 8 |
Cerebrovascular disorder | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cervical myelopathy | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Cervical radiculopathy | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Chronic inflammatory demyelinating polyradiculoneuropathy | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Coma | 0/826 (0%) | 0 | 2/822 (0.2%) | 3 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Coordination abnormal | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Diabetic mononeuropathy | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Dizziness | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 2 | 1/825 (0.1%) | 1 |
Embolic stroke | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Epilepsy | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Haemorrhage intracranial | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Haemorrhagic stroke | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 4/824 (0.5%) | 4 | 1/825 (0.1%) | 1 |
Headache | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hepatic encephalopathy | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hydrocephalus | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Hypertensive encephalopathy | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Hypoaesthesia | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hypoglycaemic unconsciousness | 5/826 (0.6%) | 5 | 3/822 (0.4%) | 3 | 1/824 (0.1%) | 1 | 3/825 (0.4%) | 6 |
Hypoxic-ischaemic encephalopathy | 1/826 (0.1%) | 2 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Intracranial aneurysm | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Intracranial hypotension | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Intraventricular haemorrhage | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Ischaemic cerebral infarction | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Ischaemic stroke | 8/826 (1%) | 8 | 7/822 (0.9%) | 8 | 16/824 (1.9%) | 16 | 4/825 (0.5%) | 4 |
Lacunar infarction | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Loss of consciousness | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Metabolic encephalopathy | 2/826 (0.2%) | 2 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 0/825 (0%) | 0 |
Migraine | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Movement disorder | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Multiple sclerosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Neuralgia | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Parkinsonism | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Presyncope | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Radiculitis lumbosacral | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Radiculopathy | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Seizure | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 3/825 (0.4%) | 3 |
Syncope | 2/826 (0.2%) | 2 | 4/822 (0.5%) | 4 | 3/824 (0.4%) | 4 | 3/825 (0.4%) | 3 |
Thalamic infarction | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Transient ischaemic attack | 7/826 (0.8%) | 8 | 6/822 (0.7%) | 7 | 10/824 (1.2%) | 10 | 7/825 (0.8%) | 7 |
VIIth nerve paralysis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
VIth nerve disorder | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Vascular parkinsonism | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Visual field defect | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Carotid artery occlusion | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Cranial nerve disorder | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hypoglycaemic coma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Myelitis transverse | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Speech disorder | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Psychiatric disorders | ||||||||
Anxiety | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Confusional state | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Delirium | 0/826 (0%) | 0 | 2/822 (0.2%) | 2 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Depression | 1/826 (0.1%) | 1 | 2/822 (0.2%) | 2 | 3/824 (0.4%) | 3 | 0/825 (0%) | 0 |
Mental status changes | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 3/825 (0.4%) | 3 |
Post-traumatic stress disorder | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Schizoaffective disorder | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Sleep terror | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Homicidal ideation | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Renal and urinary disorders | ||||||||
Acute kidney injury | 18/826 (2.2%) | 22 | 6/822 (0.7%) | 8 | 14/824 (1.7%) | 14 | 22/825 (2.7%) | 24 |
Acute prerenal failure | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Azotaemia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Bladder trabeculation | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Calculus ureteric | 3/826 (0.4%) | 3 | 3/822 (0.4%) | 3 | 2/824 (0.2%) | 2 | 1/825 (0.1%) | 1 |
Calculus urinary | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Chronic kidney disease | 10/826 (1.2%) | 10 | 5/822 (0.6%) | 5 | 14/824 (1.7%) | 17 | 5/825 (0.6%) | 5 |
Dysuria | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Glomerulonephritis chronic | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Haematuria | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Hydronephrosis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Nephrolithiasis | 2/826 (0.2%) | 2 | 3/822 (0.4%) | 3 | 1/824 (0.1%) | 1 | 3/825 (0.4%) | 3 |
Nephropathy | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Nephrotic syndrome | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 2 | 0/825 (0%) | 0 |
Proteinuria | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Renal artery arteriosclerosis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Renal colic | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Renal cyst | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Renal failure | 2/826 (0.2%) | 2 | 3/822 (0.4%) | 3 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Renal impairment | 3/826 (0.4%) | 3 | 1/822 (0.1%) | 1 | 3/824 (0.4%) | 3 | 1/825 (0.1%) | 1 |
Stag horn calculus | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Urethral stenosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Urinary bladder polyp | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Urinary incontinence | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Urinary retention | 2/826 (0.2%) | 3 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Anuria | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Diabetic end stage renal disease | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Renal artery stenosis | 0/826 (0%) | 0 | 1/822 (0.1%) | 2 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Reproductive system and breast disorders | ||||||||
Benign prostatic hyperplasia | 3/826 (0.4%) | 3 | 2/822 (0.2%) | 2 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Cystocele | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Endometrial hyperplasia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Epididymal tenderness | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Erectile dysfunction | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Menorrhagia | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Ovarian cyst | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Prostatic obstruction | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Prostatomegaly | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Testicular cyst | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Uterine polyp | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Vaginal prolapse | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Breast cyst | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Genital haemorrhage | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||
Acquired diaphragmatic eventration | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Acute pulmonary oedema | 3/826 (0.4%) | 3 | 2/822 (0.2%) | 2 | 0/824 (0%) | 0 | 2/825 (0.2%) | 2 |
Acute respiratory failure | 3/826 (0.4%) | 3 | 1/822 (0.1%) | 1 | 3/824 (0.4%) | 3 | 1/825 (0.1%) | 1 |
Asthma | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Atelectasis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Chronic obstructive pulmonary disease | 3/826 (0.4%) | 6 | 5/822 (0.6%) | 5 | 7/824 (0.8%) | 7 | 7/825 (0.8%) | 9 |
Dyspnoea | 6/826 (0.7%) | 6 | 5/822 (0.6%) | 5 | 3/824 (0.4%) | 3 | 4/825 (0.5%) | 4 |
Dyspnoea at rest | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Epistaxis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Haemoptysis | 0/826 (0%) | 0 | 1/822 (0.1%) | 3 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hydrothorax | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hypoxia | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Laryngeal stenosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Pleural effusion | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 3 | 0/825 (0%) | 0 |
Pleurisy | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Pneumonia aspiration | 0/826 (0%) | 0 | 2/822 (0.2%) | 3 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Pneumothorax | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Pulmonary congestion | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Pulmonary embolism | 2/826 (0.2%) | 2 | 4/822 (0.5%) | 4 | 3/824 (0.4%) | 3 | 4/825 (0.5%) | 4 |
Pulmonary hypertension | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Pulmonary mass | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Pulmonary oedema | 2/826 (0.2%) | 2 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 2 | 5/825 (0.6%) | 6 |
Respiratory arrest | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Respiratory distress | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Respiratory failure | 2/826 (0.2%) | 2 | 3/822 (0.4%) | 3 | 3/824 (0.4%) | 3 | 3/825 (0.4%) | 3 |
Bronchitis chronic | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Bronchospasm | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hyperventilation | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Idiopathic pulmonary fibrosis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Lung cyst | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||
Actinic keratosis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Angioedema | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Decubitus ulcer | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Diabetic foot | 6/826 (0.7%) | 8 | 2/822 (0.2%) | 2 | 3/824 (0.4%) | 3 | 5/825 (0.6%) | 8 |
Hyperkeratosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Pruritus | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Psoriasis | 1/826 (0.1%) | 2 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Rash papular | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Skin necrosis | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Skin ulcer | 3/826 (0.4%) | 3 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 2 |
Stevens-Johnson syndrome | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Surgical and medical procedures | ||||||||
Abdominal hernia repair | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Angioplasty | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Brachytherapy | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Carotid angioplasty | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Carotid artery stent insertion | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Carotid endarterectomy | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 4/825 (0.5%) | 4 |
Carotid revascularisation | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Cataract operation | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 2/825 (0.2%) | 2 |
Coronary angioplasty | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 4/824 (0.5%) | 4 | 5/825 (0.6%) | 5 |
Coronary arterial stent insertion | 15/826 (1.8%) | 19 | 8/822 (1%) | 9 | 17/824 (2.1%) | 18 | 17/825 (2.1%) | 19 |
Coronary artery bypass | 8/826 (1%) | 8 | 5/822 (0.6%) | 5 | 14/824 (1.7%) | 14 | 10/825 (1.2%) | 10 |
Coronary revascularisation | 11/826 (1.3%) | 12 | 10/822 (1.2%) | 10 | 15/824 (1.8%) | 17 | 9/825 (1.1%) | 10 |
Hospitalisation | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Laparotomy | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Mechanical ventilation | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Nasal polypectomy | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Percutaneous coronary intervention | 2/826 (0.2%) | 2 | 1/822 (0.1%) | 1 | 3/824 (0.4%) | 4 | 6/825 (0.7%) | 7 |
Peripheral artery angioplasty | 2/826 (0.2%) | 2 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 2/825 (0.2%) | 2 |
Peripheral artery bypass | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Peripheral artery stent insertion | 1/826 (0.1%) | 1 | 3/822 (0.4%) | 3 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Peripheral endarterectomy | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Peripheral revascularisation | 2/826 (0.2%) | 2 | 4/822 (0.5%) | 4 | 5/824 (0.6%) | 5 | 9/825 (1.1%) | 9 |
Pterygium operation | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Removal of internal fixation | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Stent placement | 2/826 (0.2%) | 2 | 2/822 (0.2%) | 2 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 2 |
Umbilical hernia repair | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Renal artery stent placement | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Tendon sheath incision | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Vascular disorders | ||||||||
Aortic aneurysm | 1/826 (0.1%) | 1 | 2/822 (0.2%) | 2 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Aortic dissection | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Aortic stenosis | 2/826 (0.2%) | 2 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Arterial insufficiency | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Circulatory collapse | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Deep vein thrombosis | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Extremity necrosis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Femoral artery occlusion | 1/826 (0.1%) | 1 | 2/822 (0.2%) | 2 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Haematoma | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hypertension | 1/826 (0.1%) | 1 | 1/822 (0.1%) | 1 | 3/824 (0.4%) | 3 | 3/825 (0.4%) | 3 |
Hypertensive crisis | 3/826 (0.4%) | 3 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 2/825 (0.2%) | 2 |
Hypertensive emergency | 4/826 (0.5%) | 4 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Hypotension | 2/826 (0.2%) | 2 | 0/822 (0%) | 0 | 3/824 (0.4%) | 3 | 3/825 (0.4%) | 3 |
Intra-abdominal haematoma | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Orthostatic hypotension | 2/826 (0.2%) | 2 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 1/825 (0.1%) | 1 |
Peripheral arterial occlusive disease | 3/826 (0.4%) | 3 | 2/822 (0.2%) | 2 | 1/824 (0.1%) | 1 | 3/825 (0.4%) | 3 |
Peripheral artery aneurysm | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Peripheral artery stenosis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 1/825 (0.1%) | 1 |
Peripheral artery thrombosis | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 2/824 (0.2%) | 2 | 0/825 (0%) | 0 |
Peripheral ischaemia | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Peripheral vascular disorder | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 2/824 (0.2%) | 2 | 3/825 (0.4%) | 3 |
Shock haemorrhagic | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Temporal arteritis | 1/826 (0.1%) | 1 | 0/822 (0%) | 0 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Varicose vein | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Vasculitis | 0/826 (0%) | 0 | 0/822 (0%) | 0 | 1/824 (0.1%) | 1 | 0/825 (0%) | 0 |
Femoral artery aneurysm | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Leriche syndrome | 0/826 (0%) | 0 | 1/822 (0.1%) | 1 | 0/824 (0%) | 0 | 0/825 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
Semaglutide 0.5 mg | Semaglutide 1.0 mg | Placebo 0.5 mg | Placebo 1.0 mg | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 573/826 (69.4%) | 587/822 (71.4%) | 547/824 (66.4%) | 524/825 (63.5%) | ||||
Blood and lymphatic system disorders | ||||||||
Anaemia | 41/826 (5%) | 46 | 33/822 (4%) | 34 | 44/824 (5.3%) | 46 | 48/825 (5.8%) | 55 |
Eye disorders | ||||||||
Cataract | 55/826 (6.7%) | 59 | 43/822 (5.2%) | 48 | 37/824 (4.5%) | 38 | 45/825 (5.5%) | 46 |
Diabetic retinopathy | 46/826 (5.6%) | 50 | 56/822 (6.8%) | 63 | 39/824 (4.7%) | 39 | 38/825 (4.6%) | 43 |
Gastrointestinal disorders | ||||||||
Abdominal pain | 45/826 (5.4%) | 54 | 35/822 (4.3%) | 40 | 33/824 (4%) | 37 | 31/825 (3.8%) | 36 |
Abdominal pain upper | 35/826 (4.2%) | 37 | 42/822 (5.1%) | 53 | 19/824 (2.3%) | 22 | 19/825 (2.3%) | 33 |
Constipation | 46/826 (5.6%) | 52 | 79/822 (9.6%) | 97 | 37/824 (4.5%) | 42 | 36/825 (4.4%) | 38 |
Diarrhoea | 148/826 (17.9%) | 277 | 148/822 (18%) | 245 | 97/824 (11.8%) | 159 | 87/825 (10.5%) | 112 |
Dyspepsia | 51/826 (6.2%) | 68 | 63/822 (7.7%) | 88 | 23/824 (2.8%) | 25 | 18/825 (2.2%) | 19 |
Nausea | 143/826 (17.3%) | 233 | 179/822 (21.8%) | 282 | 62/824 (7.5%) | 78 | 66/825 (8%) | 94 |
Vomiting | 87/826 (10.5%) | 128 | 122/822 (14.8%) | 170 | 42/824 (5.1%) | 51 | 33/825 (4%) | 41 |
General disorders | ||||||||
Fatigue | 24/826 (2.9%) | 27 | 42/822 (5.1%) | 48 | 15/824 (1.8%) | 16 | 26/825 (3.2%) | 28 |
Infections and infestations | ||||||||
Bronchitis | 46/826 (5.6%) | 52 | 38/822 (4.6%) | 43 | 49/824 (5.9%) | 52 | 51/825 (6.2%) | 64 |
Influenza | 51/826 (6.2%) | 60 | 48/822 (5.8%) | 56 | 48/824 (5.8%) | 57 | 46/825 (5.6%) | 63 |
Nasopharyngitis | 66/826 (8%) | 91 | 60/822 (7.3%) | 77 | 78/824 (9.5%) | 99 | 66/825 (8%) | 84 |
Upper respiratory tract infection | 53/826 (6.4%) | 59 | 51/822 (6.2%) | 64 | 63/824 (7.6%) | 75 | 65/825 (7.9%) | 88 |
Urinary tract infection | 78/826 (9.4%) | 108 | 71/822 (8.6%) | 93 | 64/824 (7.8%) | 97 | 68/825 (8.2%) | 87 |
Investigations | ||||||||
Amylase increased | 31/826 (3.8%) | 39 | 48/822 (5.8%) | 57 | 28/824 (3.4%) | 33 | 28/825 (3.4%) | 33 |
Lipase increased | 94/826 (11.4%) | 121 | 90/822 (10.9%) | 123 | 66/824 (8%) | 76 | 69/825 (8.4%) | 83 |
Metabolism and nutrition disorders | ||||||||
Decreased appetite | 86/826 (10.4%) | 97 | 75/822 (9.1%) | 88 | 19/824 (2.3%) | 21 | 9/825 (1.1%) | 10 |
Musculoskeletal and connective tissue disorders | ||||||||
Arthralgia | 41/826 (5%) | 45 | 35/822 (4.3%) | 40 | 57/824 (6.9%) | 69 | 58/825 (7%) | 70 |
Back pain | 54/826 (6.5%) | 54 | 49/822 (6%) | 58 | 49/824 (5.9%) | 59 | 48/825 (5.8%) | 50 |
Pain in extremity | 38/826 (4.6%) | 42 | 29/822 (3.5%) | 31 | 46/824 (5.6%) | 51 | 42/825 (5.1%) | 45 |
Nervous system disorders | ||||||||
Dizziness | 53/826 (6.4%) | 57 | 46/822 (5.6%) | 54 | 38/824 (4.6%) | 53 | 38/825 (4.6%) | 45 |
Headache | 54/826 (6.5%) | 77 | 58/822 (7.1%) | 89 | 67/824 (8.1%) | 114 | 74/825 (9%) | 110 |
Renal and urinary disorders | ||||||||
Microalbuminuria | 27/826 (3.3%) | 30 | 33/822 (4%) | 35 | 46/824 (5.6%) | 51 | 42/825 (5.1%) | 45 |
Respiratory, thoracic and mediastinal disorders | ||||||||
Cough | 36/826 (4.4%) | 41 | 32/822 (3.9%) | 33 | 40/824 (4.9%) | 41 | 46/825 (5.6%) | 48 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
Results Point of Contact
Name/Title | Global Clinical Registry (GCR, 1452) |
---|---|
Organization | Novo Nordisk A/S |
Phone | |
clinicaltrials@novonordisk.com |
- NN9535-3744
- 2012-002839-28
- U1111-1131-7227