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Clinical Trial Results:
An open label, active comparator extension trial to assess the effect of long term dosing of inclisiran and evolocumab given as subcutaneous injections in participants with high cardiovascular risk and elevated LDL-C (ORION-3)

Summary
EudraCT number	2016-003815-37
Trial protocol	GB DE NL
Global end of trial date	17 Dec 2021

Results information
Results version number	v2(current)
This version publication date	12 Apr 2023
First version publication date	15 Dec 2022
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

MDCO-PCS-16-01

ISRCTN number

US NCT number

NCT03060577

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharmaceuticals

Sponsor organisation address

Novartis Campus, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

17 Dec 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

17 Dec 2021

Was the trial ended prematurely?

Main objective of the trial

To assess the efficacy, safety, and tolerability of long-term dosing of inclisiran and evolocumab given as subcutaneous injections in participants with high cardiovascular risk and elevated low-density lipoprotein cholesterol (LDL-C).

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Apr 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 56

Country: Number of subjects enrolled

Germany: 49

Country: Number of subjects enrolled

United Kingdom: 69

Country: Number of subjects enrolled

Netherlands: 136

Country: Number of subjects enrolled

United States: 72

Worldwide total number of subjects

382

EEA total number of subjects

185

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

198

From 65 to 84 years

182

85 years and over

Subject disposition

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Recruitment details

Participants were recruited from 51 sites in 5 countries.

Screening details

After completion of study MDCO-PCS-15-01, participants were screened to fulfill all inclusion and exclusion criteria.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Inclisiran-only

Arm description

Participants received subcutaneous injections of inclisiran 300 milligrams (mg) on Day 1 and every 180 days thereafter up to Year 4.

Arm type

Experimental

Investigational medicinal product name

Inclisiran

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received subcutaneous injections of inclisiran 300 milligrams (mg) on Day 1 and every 180 days thereafter for up to 4 years.

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received self-administered subcutaneous injections of evolocumab 140 mg on Day 1 and every 14 days thereafter until Day 336.

Switching

Arm description

Participants received self-administered subcutaneous injections of evolocumab 140 mg on Day 1 and every 14 days thereafter until Day 336. Then, participants received subcutaneous injections of inclisiran 300 mg on Day 360 and every 180 days thereafter up to Year 4.

Arm type

Experimental

Investigational medicinal product name

Inclisiran

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received subcutaneous injections of inclisiran 300 mg on Day 360 and every 180 days thereafter for up to 4 years.

Number of subjects in period 1	Inclisiran-only	Switching
Started	290	92
Safety Analysis Set	284	90
Completed	233	80
Not completed	57	12
Consent withdrawn by subject	25	5
Physician decision	4	3
Adverse Event	9	1
Death	7	1
Other	8	2
Inclusion/Exclusion	1	-
Lost to follow-up	3	-

Baseline characteristics

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Reporting group title

Inclisiran-only

Reporting group description

Participants received subcutaneous injections of inclisiran 300 milligrams (mg) on Day 1 and every 180 days thereafter up to Year 4.

Reporting group title

Switching

Reporting group description

Reporting group values	Inclisiran-only	Switching	Total
Number of subjects	290	92	382
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	145	53	198
From 65-84 years	144	38	182
85 years and over	1	1	2
Age Continuous
Units: Year
arithmetic mean (standard deviation)	63.3 ( 11.14 )	61.9 ( 10.56 )	-
Sex: Female, Male
Units: Participants
Female	102	37	139
Male	188	55	243
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	15	7	22
Not Hispanic or Latino	275	85	360
Unknown or Not Reported	0	0	0

End points

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Reporting group title

Inclisiran-only

Reporting group description

Participants received subcutaneous injections of inclisiran 300 milligrams (mg) on Day 1 and every 180 days thereafter up to Year 4.

Reporting group title

Switching

Reporting group description

Primary: Percentage Change in LDL-C from baseline of the ORION-1 Study to Day 210 in ORION-3 (Inclisiran Arm)

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End point title

Percentage Change in LDL-C from baseline of the ORION-1 Study to Day 210 in ORION-3 (Inclisiran Arm) ^[1] ^[2]

End point description

Percent Change in LDL-C (beta-quantification) from baseline of the ORION-1 Study to Day 210 in ORION-3. A negative percentage score represents a reduction in LDL-C. Change is relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.

End point type

Primary

End point timeframe

Baseline (ORION-1) and Day 210 (ORION-3) (up to 570 days total)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint is applicable to the inclisiran arm only.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	277
Units: Percentage Change
arithmetic mean (confidence interval 95%)	-47.48 (-50.69 to -44.27)

No statistical analyses for this end point

Secondary: Percentage Change in LDL-C from baseline of the ORION-1 study (Inclisiran Arm)

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End point title

Percentage Change in LDL-C from baseline of the ORION-1 study (Inclisiran Arm) ^[3]

End point description

Percent Change in LDL-C (beta-quantification) from baseline of the ORION-1 Study overtime in ORION-3. A negative percentage score represents a reduction in LDL-C. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.

End point type

Secondary

End point timeframe

Baseline (ORION-1) and Days 30, 360, 720, 1080 and 1440 (ORION-3) (up to 390, 720, 1080, 1440 and 1800 days total, respectively)

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	277
Units: Percentage Change
arithmetic mean (confidence interval 95%)
Day 30 (n=277)	-49.43 (-52.27 to -46.58)
Day 360 (n=269)	-37.14 (-40.95 to -33.32)
Day 720 (n=253)	-38.43 (-41.75 to -35.11)
Day 1080 (n=225)	-51.07 (-54.75 to -47.39)
Day 1440 (n=232)	-46.74 (-50.71 to -42.78)

No statistical analyses for this end point

Secondary: Absolute Change in LDL-C from baseline of the ORION-1 study (Inclisiran Arm)

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End point title

Absolute Change in LDL-C from baseline of the ORION-1 study (Inclisiran Arm) ^[4]

End point description

Absolute Change in LDL-C (beta-quantification) from baseline of the ORION-1 Study overtime in ORION-3. A negative score represents a reduction in LDL-C. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.

End point type

Secondary

End point timeframe

Baseline (ORION-1) and Days 30, 360, 720, 1080 and 1440 (ORION-3) (up to 390, 720, 1080, 1440 and 1800 days total, respectively)

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	277
Units: mg/dL
arithmetic mean (confidence interval 95%)
Day 30 (n=277)	-62.51 (-66.76 to -58.25)
Day 360 (n=269)	-47.96 (-52.56 to -43.35)
Day 720 (n=253)	-49.44 (-54.25 to -44.64)
Day 1080 (n=225)	-63.34 (-68.76 to -57.92)
Day 1440 (n=232)	-60.04 (-65.81 to -54.27)

No statistical analyses for this end point

Secondary: Percentage Change in PCSK9 levels from baseline of the ORION-1 study (Inclisiran Arm)

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End point title

Percentage Change in PCSK9 levels from baseline of the ORION-1 study (Inclisiran Arm) ^[5]

End point description

Percent Change in PCSK9 from baseline of the ORION-1 Study overtime in ORION-3. A negative percentage score represents a reduction in PCSK9. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.

End point type

Secondary

End point timeframe

Baseline (ORION-1) and Days 30, 360, 720 and 1440 (ORION-3) (up to 390, 720, 1080 and 1800 days total, respectively)

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	277
Units: Percentage Change
arithmetic mean (confidence interval 95%)
Day 30 (n=277)	-71.80 (-73.17 to -70.44)
Day 360 (n=271)	-63.79 (-65.79 to -61.80)
Day 720 (n=253)	-62.17 (-64.46 to -59.88)
Day 1440 (n=228)	-69.54 (-71.19 to -67.89)

No statistical analyses for this end point

Secondary: Absolute Change in PCSK9 levels from baseline of the ORION-1 study (Inclisiran Arm)

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End point title

Absolute Change in PCSK9 levels from baseline of the ORION-1 study (Inclisiran Arm) ^[6]

End point description

Absolute Change in PCSK9 from baseline of the ORION-1 Study overtime in ORION-3. A negative score represents a reduction in PCSK9. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.

End point type

Secondary

End point timeframe

Baseline (ORION-1) and Days 30, 360, 720 and 1440 (ORION-3) (up to 390, 720, 1080 and 1800 days total, respectively)

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	277
Units: ug/L
arithmetic mean (confidence interval 95%)
Day 30 (n=277)	-314.07 (-328.69 to -299.45)
Day 360 (n=271)	-280.88 (-295.71 to -266.06)
Day 720 (n=253)	-275.78 (-291.91 to -259.64)
Day 1440 (n=228)	-314.34 (-331.22 to -297.46)

No statistical analyses for this end point

Secondary: Percentage Change in Triglycerides from baseline of the ORION-1 study (Inclisiran Arm)

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End point title

Percentage Change in Triglycerides from baseline of the ORION-1 study (Inclisiran Arm) ^[7]

End point description

Percent Change in Triglycerides from baseline of the ORION-1 Study overtime in ORION-3. A negative percentage score represents a reduction in Triglycerides. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.

End point type

Secondary

End point timeframe

Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	277
Units: Percentage Change
arithmetic mean (confidence interval 95%)
Day 30 (n=277)	-1.71 (-6.42 to 3.00)
Day 210 (n=277)	-3.35 (-9.12 to 2.41)
Day 1440 (n=232)	0.73 (-8.23 to 9.69)

No statistical analyses for this end point

Secondary: Absolute Change in Triglycerides from baseline of the ORION-1 study (Inclisiran Arm)

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End point title

Absolute Change in Triglycerides from baseline of the ORION-1 study (Inclisiran Arm) ^[8]

End point description

Absolute Change in Triglycerides from baseline of the ORION-1 Study overtime in ORION-3. A negative score represents a reduction in Triglycerides. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.

End point type

Secondary

End point timeframe

Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	277
Units: mg/dL
arithmetic mean (confidence interval 95%)
Day 30 (n=277)	-14.61 (-22.15 to -7.08)
Day 210 (n=277)	-11.96 (-23.78 to -0.14)
Day 1440 (n=232)	-14.83 (-25.75 to -3.90)

No statistical analyses for this end point

Secondary: Percentage Change in Apolipoprotein B from baseline of the ORION-1 study (Inclisiran Arm)

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End point title

Percentage Change in Apolipoprotein B from baseline of the ORION-1 study (Inclisiran Arm) ^[9]

End point description

Percent Change in Apolipoprotein B from baseline of the ORION-1 Study overtime in ORION-3. A negative percentage score represents a reduction in Apolipoprotein B. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.

End point type

Secondary

End point timeframe

Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	277
Units: Percentage Change
arithmetic mean (confidence interval 95%)
Day 30 (n=277)	-40.43 (-42.57 to -38.29)
Day 210 (n=277)	-36.65 (-39.06 to -34.23)
Day 1440 (n=226)	-33.66 (-37.18 to -30.15)

No statistical analyses for this end point

Secondary: Absolute Change in Apolipoprotein B from baseline of the ORION-1 study (Inclisiran Arm)

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End point title

Absolute Change in Apolipoprotein B from baseline of the ORION-1 study (Inclisiran Arm) ^[10]

End point description

Absolute Change in Apolipoprotein B from baseline of the ORION-1 Study overtime in ORION-3. A negative score represents a reduction in Apolipoprotein B. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.

End point type

Secondary

End point timeframe

Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	277
Units: mg/dL
arithmetic mean (confidence interval 95%)
Day 30 (n=277)	-42.63 (-45.22 to -40.04)
Day 210 (n=277)	-38.36 (-41.19 to -35.54)
Day 1440 (n=226)	-36.26 (-40.01 to -32.52)

No statistical analyses for this end point

Secondary: Percentage Change in Lipoprotein-a from baseline of the ORION-1 study (Inclisiran Arm)

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End point title

Percentage Change in Lipoprotein-a from baseline of the ORION-1 study (Inclisiran Arm) ^[11]

End point description

Percent Change in Lipoprotein-a from baseline of the ORION-1 Study overtime in ORION-3. A negative percentage score represents a reduction in Lipoprotein-a. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.

End point type

Secondary

End point timeframe

Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	277
Units: Percentage Change
arithmetic mean (confidence interval 95%)
Day 30 (n=277)	-15.88 (-19.48 to -12.28)
Day 210 (n=277)	9.29 (4.42 to 14.16)
Day 1440 (n=225)	-5.24 (-9.86 to -0.61)

No statistical analyses for this end point

Secondary: Absolute Change in Lipoprotein-a from baseline of the ORION-1 study (Inclisiran Arm)

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End point title

Absolute Change in Lipoprotein-a from baseline of the ORION-1 study (Inclisiran Arm) ^[12]

End point description

Absolute Change in Lipoprotein-a from baseline of the ORION-1 Study overtime in ORION-3. A negative score represents a reduction in Lipoprotein-a. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.

End point type

Secondary

End point timeframe

Baseline (ORION-1) and Days 30, 210 and 1440 (ORION-3) (up to 390, 570 and 1800 days total, respectively)

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	277
Units: nmol/L
arithmetic mean (confidence interval 95%)
Day 30 (n=277)	-8.52 (-12.25 to -4.79)
Day 210 (n=277)	-4.94 (-8.67 to -1.20)
Day 1440 (n=225)	-4.78 (-9.63 to 0.06)

No statistical analyses for this end point

Secondary: Number of Participants with ≥50% LDL-C Reduction from baseline of the ORION-1 study (Inclisiran Arm)

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End point title

Number of Participants with ≥50% LDL-C Reduction from baseline of the ORION-1 study (Inclisiran Arm) ^[13]

End point description

Number of Participants with ≥50% LDL-C (beta-quantification) Reduction from baseline of the ORION-1 Study overtime in ORION-3. Changes are relative to ORION-1 Baseline, which is defined as the last available record prior to first study drug administration in ORION-1.

End point type

Secondary

End point timeframe

Baseline (ORION-1) and Days 30, 360, 720 and 1440 (ORION-3) (up to 390, 720, 1080 and 1800 days total, respectively)

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	284
Units: Participants
Day 30 (n=284)	161
Day 360 (n=271)	99
Day 720 (n=255)	97
Day 1440 (n=234)	122

No statistical analyses for this end point

Secondary: Number of Participants Reaching on Treatment LDL-C Levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL (Inclisiran Arm)

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End point title

Number of Participants Reaching on Treatment LDL-C Levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL (Inclisiran Arm) ^[14]

End point description

Individual responsiveness to inclisiran is defined as the number of Participants Reaching on Treatment LDL-C Levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL at any time point.

End point type

Secondary

End point timeframe

From the start of treatment in ORION-3 to 90 days after end of treatment, assessed up to maximum duration of 4 years

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is applicable to the inclisiran arm only.

End point values	Inclisiran-only
Number of subjects analysed	284
Units: Participants
LDL-C level <25 mg/dL	82
LDL-C level <50 mg/dL	175
LDL-C level <70 mg/dL	225
LDL-C level <100 mg/dL	265

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events were reported from first dose of study treatment in ORION-3 up to end of study visit, assessed up to maximum duration of 4 years.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Inclisiran only arm

Reporting group description

Participants received subcutaneous injections of inclisiran 300 milligrams (mg) on Day 1 and every 180 days thereafter up to Year 4.

Reporting group title

Switching arm after Day 360 visit

Reporting group description

Participants received subcutaneous injections of inclisiran 300 mg on Day 360 and every 180 days thereafter up to Year 4.

Reporting group title

Switching arm up to Day 360 visit

Reporting group description

Participants received self-administered subcutaneous injections of evolocumab 140 mg on Day 1 and every 14 days thereafter until Day 336.

Serious adverse events	Inclisiran only arm	Switching arm after Day 360 visit	Switching arm up to Day 360 visit
Total subjects affected by serious adverse events
subjects affected / exposed	104 / 284 (36.62%)	30 / 87 (34.48%)	16 / 90 (17.78%)
number of deaths (all causes)	7	1	0
number of deaths resulting from adverse events	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin's disease stage IV
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Glottis carcinoma
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Follicular lymphoma
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colon cancer
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bladder transitional cell carcinoma recurrent
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Adenocarcinoma of colon
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Invasive ductal breast carcinoma
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of the tongue
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	4 / 284 (1.41%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Plasma cell myeloma
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ovarian fibroma
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Malignant melanoma
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lipoma
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Testicular seminoma (pure) stage I
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Testis cancer
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Intermittent claudication
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aortic aneurysm
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aortic aneurysm rupture
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Aortic stenosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Circulatory collapse
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Giant cell arteritis
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypertensive urgency
subjects affected / exposed	0 / 284 (0.00%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chest pain
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular stent restenosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Postmenopausal haemorrhage
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Prostatitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Uterine polyp
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary fibrosis
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Psychiatric disorders
Delirium
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Alcohol withdrawal syndrome
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post-traumatic stress disorder
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Hepatic enzyme increased
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulse abnormal
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Alcohol poisoning
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anaesthetic complication cardiac
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Incisional hernia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Postoperative wound complication
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Procedural pain
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	4 / 284 (1.41%)	2 / 87 (2.30%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	5 / 284 (1.76%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aortic valve stenosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	4 / 284 (1.41%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 5	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	7 / 284 (2.46%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 9	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Atrial tachycardia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	4 / 284 (1.41%)	3 / 87 (3.45%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 5	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coronary artery occlusion
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Mitral valve disease
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tricuspid valve incompetence
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocardial ischaemia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sinus node dysfunction
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sinus tachycardia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ventricular extrasystoles
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ventricular tachycardia
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Nervous system disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebral haemorrhage
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Carotid artery stenosis
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	4 / 284 (1.41%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sciatica
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Optic ischaemic neuropathy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Ileus
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Epiploic appendagitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhoidal haemorrhage
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	2 / 90 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haemorrhoids
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Incarcerated umbilical hernia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Obstructive pancreatitis
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Swollen tongue
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic fibrosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Diabetic foot
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urethral perforation
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Osteoporosis
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	6 / 284 (2.11%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 6	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthralgia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bone pain
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tendon disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal stenosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Escherichia sepsis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	6 / 284 (2.11%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 6	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0
Cellulitis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infected bite
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Localised infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	4 / 284 (1.41%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal sepsis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia pneumococcal
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetes mellitus inadequate control
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lactic acidosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Inclisiran only arm	Switching arm after Day 360 visit	Switching arm up to Day 360 visit
Total subjects affected by non serious adverse events
subjects affected / exposed	271 / 284 (95.42%)	77 / 87 (88.51%)	78 / 90 (86.67%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	11 / 284 (3.87%)	3 / 87 (3.45%)	0 / 90 (0.00%)
occurrences all number	13	3	0
Blepharal papilloma
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Bowen's disease
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Malignant melanoma
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Fibroma
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Haemangioma of liver
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Hypergammaglobulinaemia benign monoclonal
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Intraductal papillary mucinous neoplasm
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Lipoma
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	2 / 90 (2.22%)
occurrences all number	2	1	2
Colon adenoma
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Melanocytic naevus
subjects affected / exposed	0 / 284 (0.00%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	0	2	0
Oral papilloma
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Ovarian fibroma
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Papilloma
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Phaeochromocytoma
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Plasma cell myeloma
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Prostatic adenoma
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Seborrhoeic keratosis
subjects affected / exposed	0 / 284 (0.00%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	0	2	0
Squamous cell carcinoma of skin
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Meningioma
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Vascular disorders
Circulatory collapse
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Aortic aneurysm
subjects affected / exposed	2 / 284 (0.70%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	2	2	0
Aortic arteriosclerosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Aortic dilatation
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Aortic stenosis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Deep vein thrombosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Extremity necrosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Flushing
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Hot flush
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Hypertension
subjects affected / exposed	42 / 284 (14.79%)	17 / 87 (19.54%)	2 / 90 (2.22%)
occurrences all number	47	18	2
Orthostatic hypotension
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Hypertensive urgency
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Hypotension
subjects affected / exposed	6 / 284 (2.11%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	6	1	0
Intermittent claudication
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Lymphoedema
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hypertensive crisis
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	2	0
Peripheral arterial occlusive disease
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	4	1	0
Peripheral coldness
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Varicose vein
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Peripheral venous disease
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Post thrombotic syndrome
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Thrombosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Varicophlebitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Peripheral vascular disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Surgical and medical procedures
Abortion induced
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
General disorders and administration site conditions
Adverse drug reaction
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Asthenia
subjects affected / exposed	5 / 284 (1.76%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	5	0	0
Chest discomfort
subjects affected / exposed	5 / 284 (1.76%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	5	1	0
Chest pain
subjects affected / exposed	6 / 284 (2.11%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	6	1	1
Chills
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Complication of device insertion
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Gait disturbance
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Cyst
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Discomfort
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Drug intolerance
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	2
Face oedema
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Fatigue
subjects affected / exposed	23 / 284 (8.10%)	10 / 87 (11.49%)	3 / 90 (3.33%)
occurrences all number	26	11	3
Feeling abnormal
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Crepitations
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hernia
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Injection site vesicles
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Injection site bruising
subjects affected / exposed	4 / 284 (1.41%)	3 / 87 (3.45%)	4 / 90 (4.44%)
occurrences all number	5	3	6
Injection site discolouration
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Injection site erythema
subjects affected / exposed	12 / 284 (4.23%)	3 / 87 (3.45%)	0 / 90 (0.00%)
occurrences all number	21	4	0
Injection site haematoma
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Injection site haemorrhage
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	2	0	1
Injection site oedema
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Injection site pain
subjects affected / exposed	12 / 284 (4.23%)	4 / 87 (4.60%)	0 / 90 (0.00%)
occurrences all number	23	4	0
Injection site paraesthesia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	2	0
Injection site pruritus
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Injection site rash
subjects affected / exposed	8 / 284 (2.82%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	14	1	0
Injection site reaction
subjects affected / exposed	16 / 284 (5.63%)	4 / 87 (4.60%)	2 / 90 (2.22%)
occurrences all number	33	6	2
Injection site urticaria
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Influenza like illness
subjects affected / exposed	15 / 284 (5.28%)	3 / 87 (3.45%)	2 / 90 (2.22%)
occurrences all number	19	3	2
Injection site warmth
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	2
Medical device complication
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Multiple organ dysfunction syndrome
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Nodule
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Non-cardiac chest pain
subjects affected / exposed	13 / 284 (4.58%)	4 / 87 (4.60%)	1 / 90 (1.11%)
occurrences all number	17	4	1
Oedema peripheral
subjects affected / exposed	11 / 284 (3.87%)	6 / 87 (6.90%)	2 / 90 (2.22%)
occurrences all number	11	6	2
Pain
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Peripheral swelling
subjects affected / exposed	4 / 284 (1.41%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	4	1	1
Polyp
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Pyrexia
subjects affected / exposed	4 / 284 (1.41%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	4	0	1
Vessel puncture site bruise
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Vessel puncture site induration
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Malaise
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Immune system disorders
Allergy to animal
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Allergy to arthropod bite
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Allergy to arthropod sting
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Food allergy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	2
Hypersensitivity
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Mite allergy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Seasonal allergy
subjects affected / exposed	3 / 284 (1.06%)	2 / 87 (2.30%)	2 / 90 (2.22%)
occurrences all number	4	2	2
Drug hypersensitivity
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Rubber sensitivity
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Reproductive system and breast disorders
Breast tenderness
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Atrophic vulvovaginitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Balanoposthitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Benign prostatic hyperplasia
subjects affected / exposed	8 / 284 (2.82%)	3 / 87 (3.45%)	0 / 90 (0.00%)
occurrences all number	8	4	0
Breast disorder female
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Breast pain
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	4	0	0
Cervix disorder
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Erectile dysfunction
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	2	0	1
Genital rash
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Gynaecomastia
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Haematospermia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Heavy menstrual bleeding
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Menopausal symptoms
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Penile erythema
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Postmenopausal haemorrhage
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	1	1	1
Prostatitis
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Pruritus genital
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Scrotal pain
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Spermatocele
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Testicular swelling
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Uterine polyp
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Vaginal dysplasia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Vulvovaginal pain
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Vulvovaginal pruritus
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Abnormal uterine bleeding
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	22 / 284 (7.75%)	5 / 87 (5.75%)	2 / 90 (2.22%)
occurrences all number	22	6	2
Bronchospasm
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Chronic obstructive pulmonary disease
subjects affected / exposed	7 / 284 (2.46%)	2 / 87 (2.30%)	1 / 90 (1.11%)
occurrences all number	11	3	2
Cough
subjects affected / exposed	22 / 284 (7.75%)	5 / 87 (5.75%)	1 / 90 (1.11%)
occurrences all number	25	5	1
Dry throat
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Dysphonia
subjects affected / exposed	3 / 284 (1.06%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	3	2	0
Asthma
subjects affected / exposed	10 / 284 (3.52%)	4 / 87 (4.60%)	1 / 90 (1.11%)
occurrences all number	13	4	1
Dyspnoea exertional
subjects affected / exposed	10 / 284 (3.52%)	5 / 87 (5.75%)	0 / 90 (0.00%)
occurrences all number	10	5	0
Emphysema
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Epistaxis
subjects affected / exposed	10 / 284 (3.52%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	11	0	1
Hiccups
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Hypoxia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Lung infiltration
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Pneumothorax
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Nasal obstruction
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Nasal polyps
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Nasal septum deviation
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Oropharyngeal pain
subjects affected / exposed	8 / 284 (2.82%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	8	1	1
Pleural effusion
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Nasal congestion
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	1	1	1
Pulmonary calcification
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Pulmonary embolism
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Pulmonary hypertension
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Pulmonary mass
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Reflux laryngitis
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Sinus disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Respiratory distress
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	4
Respiratory tract congestion
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Rhinorrhoea
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	2 / 90 (2.22%)
occurrences all number	1	0	2
Sinonasal obstruction
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Sinus congestion
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	1	1	1
Respiratory disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Sinus polyp
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Sleep apnoea syndrome
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Sneezing
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	3	0	1
Throat irritation
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Upper respiratory tract irritation
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Wheezing
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Upper-airway cough syndrome
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Psychiatric disorders
Acute stress disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Adjustment disorder with depressed mood
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Agitation
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Alcoholism
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Anxiety
subjects affected / exposed	4 / 284 (1.41%)	1 / 87 (1.15%)	2 / 90 (2.22%)
occurrences all number	4	1	2
Anxiety disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Disorientation
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Confusional state
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Delirium
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Depressed mood
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Depression
subjects affected / exposed	12 / 284 (4.23%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	12	0	0
Burnout syndrome
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Emotional disorder
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Emotional distress
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Fear
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Indifference
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Insomnia
subjects affected / exposed	10 / 284 (3.52%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	10	1	1
Panic attack
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Seasonal affective disorder
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Stress
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Nightmare
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	0	1	1
Product issues
Device dislocation
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Prosthetic cardiac valve failure
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hepatobiliary disorders
Hepatic cyst
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Cholecystitis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Cholelithiasis
subjects affected / exposed	7 / 284 (2.46%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	7	0	0
Hepatic fibrosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hepatic function abnormal
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hepatic steatosis
subjects affected / exposed	5 / 284 (1.76%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	6	2	0
Investigations
Activated partial thromboplastin time prolonged
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Alanine aminotransferase increased
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	4	1	1
Aspartate aminotransferase increased
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	2	1	1
Blood alkaline phosphatase increased
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Blood bilirubin increased
subjects affected / exposed	4 / 284 (1.41%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	4	0	0
Blood calcium increased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	10 / 284 (3.52%)	0 / 87 (0.00%)	2 / 90 (2.22%)
occurrences all number	10	0	2
Blood creatinine increased
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Blood folate decreased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Blood glucose abnormal
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Blood glucose increased
subjects affected / exposed	5 / 284 (1.76%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	5	1	1
Blood potassium decreased
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Blood potassium increased
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Blood pressure increased
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	1	1	1
Blood sodium decreased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
C-reactive protein increased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Blood uric acid decreased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Blood uric acid increased
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Blood urine present
subjects affected / exposed	5 / 284 (1.76%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	5	0	0
Body temperature increased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Blood urea increased
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Carbohydrate antigen 19-9 increased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Carcinoembryonic antigen increased
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Cardiac murmur
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Carotid bruit
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Electrocardiogram abnormal
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Haemoglobin decreased
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Gamma-glutamyltransferase increased
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	3	1	0
Glomerular filtration rate decreased
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Glycosylated haemoglobin increased
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Haematocrit decreased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Gamma-glutamyltransferase abnormal
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Heart rate decreased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Heart rate irregular
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Hepatic enzyme increased
subjects affected / exposed	9 / 284 (3.17%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	9	2	0
International normalised ratio increased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Intraocular pressure increased
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Neutrophil count increased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Lipoprotein increased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Liver function test abnormal
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Liver function test increased
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Low density lipoprotein increased
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Mean cell volume increased
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Lipoprotein (a) increased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Platelet count decreased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Vitamin D decreased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Prostatic specific antigen increased
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Pulmonary function test decreased
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Pulse absent
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
QRS axis abnormal
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
SARS-CoV-2 test positive
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Sinus rhythm
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Spirometry abnormal
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Streptococcus test positive
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Thyroid function test abnormal
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Troponin T increased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Urine analysis abnormal
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Vitamin B12 decreased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Platelet count increased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Weight decreased
subjects affected / exposed	1 / 284 (0.35%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	1	2	0
Weight increased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
White blood cell count increased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Injury, poisoning and procedural complications
Back injury
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Anaemia postoperative
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Animal bite
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Ankle fracture
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Arthropod bite
subjects affected / exposed	5 / 284 (1.76%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	5	0	0
Bone contusion
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Burns second degree
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Cervical vertebral fracture
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Chest injury
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Concussion
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	3 / 90 (3.33%)
occurrences all number	2	0	3
Contusion
subjects affected / exposed	15 / 284 (5.28%)	3 / 87 (3.45%)	2 / 90 (2.22%)
occurrences all number	18	5	3
Forearm fracture
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Eye contusion
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Facial bones fracture
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	0	1	1
Fall
subjects affected / exposed	24 / 284 (8.45%)	2 / 87 (2.30%)	1 / 90 (1.11%)
occurrences all number	34	3	1
Fibula fracture
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Foot fracture
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	4	1	0
Epicondylitis
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	5	1	0
Foreign body
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hand fracture
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Head injury
subjects affected / exposed	4 / 284 (1.41%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	4	0	0
Hip fracture
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Incisional hernia
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Incorrect dose administered
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Limb injury
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	3 / 90 (3.33%)
occurrences all number	2	1	3
Injection related reaction
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	3
Injury
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Joint dislocation
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Joint injury
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Ligament rupture
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Ligament sprain
subjects affected / exposed	5 / 284 (1.76%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	6	0	0
Inflammation of wound
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Muscle strain
subjects affected / exposed	4 / 284 (1.41%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	7	0	0
Muscle rupture
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Overdose
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Patella fracture
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Periorbital haematoma
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Post procedural complication
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Post procedural oedema
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Post procedural swelling
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Post-traumatic neck syndrome
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Lip injury
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Lower limb fracture
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Lumbar vertebral fracture
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Medication error
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Meniscus injury
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Musculoskeletal injury
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Post-traumatic pain
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Postoperative ileus
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Procedural pain
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	3	1	1
Product dispensing error
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Radius fracture
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Reactive gastropathy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Thermal burn
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Road traffic accident
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	2 / 90 (2.22%)
occurrences all number	3	1	2
Skin abrasion
subjects affected / exposed	6 / 284 (2.11%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	6	0	1
Skin laceration
subjects affected / exposed	2 / 284 (0.70%)	3 / 87 (3.45%)	0 / 90 (0.00%)
occurrences all number	2	3	0
Sunburn
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Tendon injury
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Tendon rupture
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Rib fracture
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	3	1	0
Tibia fracture
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Tooth fracture
subjects affected / exposed	5 / 284 (1.76%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	5	0	0
Traumatic haematoma
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Traumatic liver injury
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Traumatic shock
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Wrist fracture
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	2 / 90 (2.22%)
occurrences all number	1	0	2
Ulnar nerve injury
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Upper limb fracture
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Vaccination complication
subjects affected / exposed	6 / 284 (2.11%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	7	0	0
Wound
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Wound haemorrhage
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Ulna fracture
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Wrong dose
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Congenital, familial and genetic disorders
Phimosis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Corneal dystrophy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hydrocele
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Cardiac disorders
Angina pectoris
subjects affected / exposed	17 / 284 (5.99%)	5 / 87 (5.75%)	4 / 90 (4.44%)
occurrences all number	20	6	4
Aortic valve incompetence
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	3	1	0
Aortic valve stenosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Arrhythmia
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Atrioventricular block first degree
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	3	1	0
Atrial flutter
subjects affected / exposed	2 / 284 (0.70%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	3	2	0
Atrial thrombosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Atrial fibrillation
subjects affected / exposed	10 / 284 (3.52%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	14	2	0
Bradycardia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Bundle branch block left
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Bundle branch block right
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	3	1	0
Cardiac failure
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Cardiac failure congestive
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	3	2	0
Coronary artery aneurysm
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Mitral valve incompetence
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Coronary artery occlusion
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Coronary artery stenosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Dilatation atrial
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Extrasystoles
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Ischaemic cardiomyopathy
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Left ventricular dysfunction
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Coronary artery disease
subjects affected / exposed	4 / 284 (1.41%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	5	1	1
Mitral valve prolapse
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Palpitations
subjects affected / exposed	7 / 284 (2.46%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	8	1	1
Pericardial effusion
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Right ventricular dilatation
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Sinus bradycardia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Supraventricular tachycardia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Tachycardia
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Tricuspid valve incompetence
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Ventricular extrasystoles
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	2	0	1
Ventricular hypokinesia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Ventricular tachycardia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	0	2	1
Myocardial ischaemia
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Nervous system disorders
Balance disorder
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Ageusia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Altered state of consciousness
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Amnesia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Anosmia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Burning sensation
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Carotid arteriosclerosis
subjects affected / exposed	0 / 284 (0.00%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	0	2	0
Carotid artery stenosis
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Carpal tunnel syndrome
subjects affected / exposed	3 / 284 (1.06%)	2 / 87 (2.30%)	1 / 90 (1.11%)
occurrences all number	4	2	1
Cerebral haemorrhage
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Cerebral infarction
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Disturbance in attention
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Cervical radiculopathy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Cluster headache
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Cognitive disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Cubital tunnel syndrome
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Diabetic neuropathy
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	3	0	1
Cerebrovascular accident
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Dizziness
subjects affected / exposed	24 / 284 (8.45%)	5 / 87 (5.75%)	4 / 90 (4.44%)
occurrences all number	27	6	5
Dizziness postural
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Dysarthria
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Dysgeusia
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Epilepsy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Head discomfort
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Muscle tension dysphonia
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Hypoaesthesia
subjects affected / exposed	4 / 284 (1.41%)	2 / 87 (2.30%)	2 / 90 (2.22%)
occurrences all number	4	2	2
Loss of consciousness
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Lumbosacral radiculopathy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Memory impairment
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Migraine
subjects affected / exposed	2 / 284 (0.70%)	2 / 87 (2.30%)	1 / 90 (1.11%)
occurrences all number	2	3	1
Migraine with aura
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Headache
subjects affected / exposed	21 / 284 (7.39%)	7 / 87 (8.05%)	8 / 90 (8.89%)
occurrences all number	26	8	11
Nerve compression
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Nervous system disorder
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Neuropathy peripheral
subjects affected / exposed	2 / 284 (0.70%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	2	2	0
Occipital neuralgia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	0	1	1
Ophthalmic migraine
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Presyncope
subjects affected / exposed	5 / 284 (1.76%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	5	1	1
Parkinson's disease
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Parkinsonism
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Piriformis syndrome
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Polyneuropathy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Post herpetic neuralgia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Paraesthesia
subjects affected / exposed	7 / 284 (2.46%)	3 / 87 (3.45%)	1 / 90 (1.11%)
occurrences all number	8	3	1
Restless legs syndrome
subjects affected / exposed	1 / 284 (0.35%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	1	3	0
Sciatica
subjects affected / exposed	3 / 284 (1.06%)	3 / 87 (3.45%)	1 / 90 (1.11%)
occurrences all number	3	3	1
Sensory loss
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Somnolence
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Syncope
subjects affected / exposed	4 / 284 (1.41%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	6	2	0
Tremor
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Vascular dementia
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Taste disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	6 / 284 (2.11%)	2 / 87 (2.30%)	4 / 90 (4.44%)
occurrences all number	6	2	4
Eosinophilia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Increased tendency to bruise
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Iron deficiency anaemia
subjects affected / exposed	4 / 284 (1.41%)	2 / 87 (2.30%)	1 / 90 (1.11%)
occurrences all number	4	2	1
Lymphadenopathy
subjects affected / exposed	1 / 284 (0.35%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	1	2	0
Neutropenia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Thrombocytopenia
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
White blood cell disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Microcytic anaemia
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	3	1	0
Ear and labyrinth disorders
Deafness bilateral
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Deafness neurosensory
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Deafness unilateral
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Ear pain
subjects affected / exposed	4 / 284 (1.41%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	4	0	1
Ear swelling
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Excessive cerumen production
subjects affected / exposed	2 / 284 (0.70%)	3 / 87 (3.45%)	1 / 90 (1.11%)
occurrences all number	2	3	1
Tinnitus
subjects affected / exposed	2 / 284 (0.70%)	2 / 87 (2.30%)	1 / 90 (1.11%)
occurrences all number	2	2	1
Vertigo
subjects affected / exposed	9 / 284 (3.17%)	3 / 87 (3.45%)	1 / 90 (1.11%)
occurrences all number	9	3	1
Vertigo positional
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Vestibular disorder
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Hypoacusis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Eye disorders
Blepharitis
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Cataract
subjects affected / exposed	15 / 284 (5.28%)	3 / 87 (3.45%)	0 / 90 (0.00%)
occurrences all number	20	3	0
Chalazion
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Conjunctival haemorrhage
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Glaucoma
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	2
Dacryostenosis acquired
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Diplopia
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Dry eye
subjects affected / exposed	4 / 284 (1.41%)	3 / 87 (3.45%)	0 / 90 (0.00%)
occurrences all number	4	3	0
Entropion
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Epiretinal membrane
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Eye swelling
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	0	1	1
Corneal erosion
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Meibomianitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Metamorphopsia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Ocular hyperaemia
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Ocular hypertension
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Photophobia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Meibomian gland dysfunction
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Iritis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Lacrimal mucocoele
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Lacrimation decreased
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Macular degeneration
subjects affected / exposed	4 / 284 (1.41%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	4	1	2
Macular hole
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	2	0
Retinal artery embolism
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Retinal haemorrhage
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Retinal vein occlusion
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	0	1	1
Retinopathy hypertensive
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Vision blurred
subjects affected / exposed	1 / 284 (0.35%)	2 / 87 (2.30%)	1 / 90 (1.11%)
occurrences all number	1	2	1
Visual impairment
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Vitreous detachment
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Vitreous floaters
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	10 / 284 (3.52%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	10	0	0
Abdominal distension
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Abdominal hernia
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Abdominal pain
subjects affected / exposed	13 / 284 (4.58%)	3 / 87 (3.45%)	4 / 90 (4.44%)
occurrences all number	15	3	6
Abdominal pain lower
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Abdominal pain upper
subjects affected / exposed	5 / 284 (1.76%)	2 / 87 (2.30%)	3 / 90 (3.33%)
occurrences all number	7	3	4
Anal haemorrhage
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Aphthous ulcer
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Dysphagia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Dyspepsia
subjects affected / exposed	7 / 284 (2.46%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	7	2	0
Dry mouth
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Diverticulum intestinal
subjects affected / exposed	2 / 284 (0.70%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	2	2	0
Diverticulum
subjects affected / exposed	5 / 284 (1.76%)	4 / 87 (4.60%)	1 / 90 (1.11%)
occurrences all number	6	4	1
Barrett's oesophagus
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Dental caries
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Defaecation urgency
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Constipation
subjects affected / exposed	15 / 284 (5.28%)	5 / 87 (5.75%)	5 / 90 (5.56%)
occurrences all number	15	5	5
Colitis ulcerative
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Chronic gastritis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Buccal polyp
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Diarrhoea
subjects affected / exposed	17 / 284 (5.99%)	9 / 87 (10.34%)	3 / 90 (3.33%)
occurrences all number	18	9	3
Enteritis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Faeces discoloured
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Food poisoning
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Gastric disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Gastric ulcer
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	0	1	1
Gastritis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	2	0	1
Gastritis erosive
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Gastrointestinal disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Gastrointestinal motility disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Gastrointestinal scarring
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	6 / 284 (2.11%)	5 / 87 (5.75%)	2 / 90 (2.22%)
occurrences all number	6	6	2
Haematochezia
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Flatulence
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	1	1	1
Hiatus hernia
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	2	0	1
Haemorrhoids
subjects affected / exposed	5 / 284 (1.76%)	1 / 87 (1.15%)	2 / 90 (2.22%)
occurrences all number	5	1	2
Haemorrhoidal haemorrhage
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Incarcerated umbilical hernia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Inguinal hernia
subjects affected / exposed	6 / 284 (2.11%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	6	2	0
Intestinal polyp
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Irritable bowel syndrome
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Large intestine polyp
subjects affected / exposed	9 / 284 (3.17%)	3 / 87 (3.45%)	1 / 90 (1.11%)
occurrences all number	10	3	1
Levator syndrome
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Malpositioned teeth
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Melaena
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Mouth ulceration
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Nausea
subjects affected / exposed	18 / 284 (6.34%)	6 / 87 (6.90%)	3 / 90 (3.33%)
occurrences all number	19	6	3
Impaired gastric emptying
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Oesophageal obstruction
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Oesophageal spasm
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Vomiting
subjects affected / exposed	6 / 284 (2.11%)	1 / 87 (1.15%)	2 / 90 (2.22%)
occurrences all number	9	1	2
Umbilical hernia
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Toothache
subjects affected / exposed	8 / 284 (2.82%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	8	0	0
Tooth disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Swollen tongue
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Salivary gland enlargement
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Salivary gland disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Rectal polyp
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Rectal haemorrhage
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	8	0	0
Oesophagitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Pancreatic failure
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Pancreatic steatosis
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Acne
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Actinic elastosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Actinic keratosis
subjects affected / exposed	4 / 284 (1.41%)	2 / 87 (2.30%)	1 / 90 (1.11%)
occurrences all number	6	1	1
Blister
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Lichen planus
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Dermatitis
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	2	1	1
Dry skin
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Ecchymosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Eczema
subjects affected / exposed	4 / 284 (1.41%)	2 / 87 (2.30%)	2 / 90 (2.22%)
occurrences all number	4	2	2
Eczema nummular
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Erythema
subjects affected / exposed	4 / 284 (1.41%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	6	0	0
Hand dermatitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hidradenitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hyperhidrosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hyperkeratosis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Ingrowing nail
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Keloid scar
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Dermal cyst
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Lichenoid keratosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Seborrhoeic dermatitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Nail dystrophy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Neurodermatitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Night sweats
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	4	1	0
Penile ulceration
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Petechiae
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Precancerous skin lesion
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Pruritus
subjects affected / exposed	11 / 284 (3.87%)	3 / 87 (3.45%)	2 / 90 (2.22%)
occurrences all number	16	4	2
Psoriasis
subjects affected / exposed	5 / 284 (1.76%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	5	0	0
Rash
subjects affected / exposed	11 / 284 (3.87%)	1 / 87 (1.15%)	2 / 90 (2.22%)
occurrences all number	11	1	2
Rash erythematous
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	2
Rosacea
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	1	1	1
Scab
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Nail discolouration
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Skin depigmentation
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Skin fissures
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Skin induration
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Skin lesion
subjects affected / exposed	6 / 284 (2.11%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	6	1	0
Skin ulcer
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Stasis dermatitis
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Vitiligo
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Xanthoma
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Skin discolouration
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Renal and urinary disorders
Albuminuria
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Acute kidney injury
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Bladder cyst
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Calculus bladder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Chronic kidney disease
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	1	1	1
Cystitis noninfective
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Dysuria
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Glycosuria
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Microalbuminuria
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hydronephrosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hypertonic bladder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Incontinence
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Leukocyturia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Lower urinary tract symptoms
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Haematuria
subjects affected / exposed	9 / 284 (3.17%)	3 / 87 (3.45%)	1 / 90 (1.11%)
occurrences all number	12	3	1
Nephrolithiasis
subjects affected / exposed	4 / 284 (1.41%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	4	0	0
Nephropathy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Nocturia
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Pollakiuria
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	3	0	1
Polyuria
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Myoglobinuria
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Renal artery stenosis
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Renal colic
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Renal cyst
subjects affected / exposed	4 / 284 (1.41%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	4	3	0
Micturition disorder
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Micturition urgency
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Proteinuria
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	3	1	0
Renal failure
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Renal impairment
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	3	1	1
Ureteral disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Urinary incontinence
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Urinary retention
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Urinary tract discomfort
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	4 / 284 (1.41%)	2 / 87 (2.30%)	1 / 90 (1.11%)
occurrences all number	4	2	1
Goitre
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Hyperthyroidism
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Thyroid cyst
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Thyroid mass
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	40 / 284 (14.08%)	10 / 87 (11.49%)	10 / 90 (11.11%)
occurrences all number	53	17	11
Arthritis
subjects affected / exposed	5 / 284 (1.76%)	3 / 87 (3.45%)	1 / 90 (1.11%)
occurrences all number	5	4	1
Arthritis reactive
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Axillary mass
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Back pain
subjects affected / exposed	28 / 284 (9.86%)	13 / 87 (14.94%)	1 / 90 (1.11%)
occurrences all number	36	14	1
Coccydynia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Bone pain
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Bursitis
subjects affected / exposed	9 / 284 (3.17%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	10	0	0
Cervical spinal stenosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Chondropathy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Bone atrophy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Costochondritis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Dupuytren's contracture
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Enthesopathy
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Exostosis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Exostosis of jaw
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Femoroacetabular impingement
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Fibromyalgia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Finger deformity
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Foot deformity
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Groin pain
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Intervertebral disc degeneration
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Intervertebral disc disorder
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Intervertebral disc protrusion
subjects affected / exposed	4 / 284 (1.41%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	5	0	0
Joint stiffness
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Joint swelling
subjects affected / exposed	4 / 284 (1.41%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	7	0	0
Limb discomfort
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Loose body in joint
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Lumbar spinal stenosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Muscle spasms
subjects affected / exposed	15 / 284 (5.28%)	2 / 87 (2.30%)	6 / 90 (6.67%)
occurrences all number	19	2	6
Muscle tightness
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Osteitis
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Musculoskeletal chest pain
subjects affected / exposed	5 / 284 (1.76%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	6	1	0
Musculoskeletal pain
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	2	0	1
Musculoskeletal stiffness
subjects affected / exposed	2 / 284 (0.70%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	3	2	0
Myalgia
subjects affected / exposed	24 / 284 (8.45%)	3 / 87 (3.45%)	7 / 90 (7.78%)
occurrences all number	28	4	7
Neck pain
subjects affected / exposed	4 / 284 (1.41%)	2 / 87 (2.30%)	1 / 90 (1.11%)
occurrences all number	4	2	1
Muscular weakness
subjects affected / exposed	5 / 284 (1.76%)	1 / 87 (1.15%)	2 / 90 (2.22%)
occurrences all number	6	1	2
Osteoarthritis
subjects affected / exposed	16 / 284 (5.63%)	6 / 87 (6.90%)	2 / 90 (2.22%)
occurrences all number	18	6	2
Osteochondrosis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Osteopenia
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Osteoporosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Rheumatoid arthritis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Periarthritis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Plantar fasciitis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Polyarthritis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Polymyalgia rheumatica
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Pain in extremity
subjects affected / exposed	25 / 284 (8.80%)	6 / 87 (6.90%)	1 / 90 (1.11%)
occurrences all number	29	7	1
Spinal osteoarthritis
subjects affected / exposed	6 / 284 (2.11%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	7	0	0
Spinal pain
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Spinal stenosis
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Spondyloarthropathy
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Spondylolisthesis
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Synovial cyst
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Spinal deformity
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Tendon pain
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Tendonitis
subjects affected / exposed	3 / 284 (1.06%)	4 / 87 (4.60%)	1 / 90 (1.11%)
occurrences all number	3	4	1
Rotator cuff syndrome
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	3	1	1
Shoulder deformity
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Sjogren's syndrome
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Synovitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Tenosynovitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Trigger finger
subjects affected / exposed	5 / 284 (1.76%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	6	0	0
Infections and infestations
Acarodermatitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Abscess
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Abscess of eyelid
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Bronchitis
subjects affected / exposed	15 / 284 (5.28%)	4 / 87 (4.60%)	3 / 90 (3.33%)
occurrences all number	19	5	3
Balanitis candida
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Candida infection
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Cellulitis
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Clostridium difficile infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Conjunctivitis
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	4	1	0
Corneal infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Coronavirus infection
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Cystitis
subjects affected / exposed	5 / 284 (1.76%)	6 / 87 (6.90%)	2 / 90 (2.22%)
occurrences all number	6	8	2
Diarrhoea infectious
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Acute sinusitis
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Asymptomatic bacteriuria
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Bacterial infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Bacteriuria
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
COVID-19
subjects affected / exposed	3 / 284 (1.06%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	3	2	0
Diverticulitis
subjects affected / exposed	5 / 284 (1.76%)	2 / 87 (2.30%)	2 / 90 (2.22%)
occurrences all number	5	2	2
Ear infection
subjects affected / exposed	1 / 284 (0.35%)	5 / 87 (5.75%)	1 / 90 (1.11%)
occurrences all number	1	6	1
Ear lobe infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Erysipelas
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Escherichia bacteraemia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
External ear cellulitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Eye infection
subjects affected / exposed	3 / 284 (1.06%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	3	1	0
Folliculitis
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Fungal infection
subjects affected / exposed	5 / 284 (1.76%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	6	0	0
Fungal skin infection
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	3	0	1
Furuncle
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Gastroenteritis
subjects affected / exposed	12 / 284 (4.23%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	12	0	1
Gastroenteritis bacterial
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Gastroenteritis viral
subjects affected / exposed	8 / 284 (2.82%)	2 / 87 (2.30%)	2 / 90 (2.22%)
occurrences all number	8	2	2
Genital herpes simplex
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Genital infection fungal
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Gingivitis
subjects affected / exposed	0 / 284 (0.00%)	3 / 87 (3.45%)	0 / 90 (0.00%)
occurrences all number	0	3	0
Helicobacter infection
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Hepatitis C
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Herpes simplex
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Influenza
subjects affected / exposed	36 / 284 (12.68%)	10 / 87 (11.49%)	6 / 90 (6.67%)
occurrences all number	42	12	8
Hordeolum
subjects affected / exposed	5 / 284 (1.76%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	7	0	0
Impetigo
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Infective exacerbation of bronchiectasis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Infective exacerbation of chronic obstructive airways disease
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Herpes zoster
subjects affected / exposed	12 / 284 (4.23%)	3 / 87 (3.45%)	1 / 90 (1.11%)
occurrences all number	13	3	1
Kidney infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Orchitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Labyrinthitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Localised infection
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Lower respiratory tract infection
subjects affected / exposed	11 / 284 (3.87%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	23	3	1
Mastitis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Nail infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Nasopharyngitis
subjects affected / exposed	55 / 284 (19.37%)	13 / 87 (14.94%)	6 / 90 (6.67%)
occurrences all number	73	14	7
Onychomycosis
subjects affected / exposed	4 / 284 (1.41%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	4	0	0
Ophthalmic herpes zoster
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Oral candidiasis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Oral fungal infection
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Oral herpes
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Oral infection
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Klebsiella infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Respiratory tract infection
subjects affected / exposed	2 / 284 (0.70%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	2	2	0
Respiratory tract infection viral
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Otitis externa
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Otitis media
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Paronychia
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Perichondritis
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	1 / 90 (1.11%)
occurrences all number	0	1	1
Respiratory syncytial virus infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Pneumonia
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	2 / 90 (2.22%)
occurrences all number	4	1	2
Pneumonia viral
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Postoperative wound infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Pulpitis dental
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Pyelonephritis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Rash pustular
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Pharyngitis
subjects affected / exposed	3 / 284 (1.06%)	3 / 87 (3.45%)	0 / 90 (0.00%)
occurrences all number	3	3	0
Retinitis
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Urinary tract infection bacterial
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Root canal infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Sebaceous gland infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Sinusitis
subjects affected / exposed	10 / 284 (3.52%)	3 / 87 (3.45%)	3 / 90 (3.33%)
occurrences all number	11	4	3
Skin infection
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	5	0	0
Staphylococcal infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Suspected COVID-19
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Tinea cruris
subjects affected / exposed	0 / 284 (0.00%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	0	2	0
Tooth abscess
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	3	1	0
Tooth infection
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	2 / 90 (2.22%)
occurrences all number	4	0	2
Upper respiratory tract infection
subjects affected / exposed	24 / 284 (8.45%)	5 / 87 (5.75%)	1 / 90 (1.11%)
occurrences all number	31	7	1
Urethritis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Urinary tract infection
subjects affected / exposed	37 / 284 (13.03%)	7 / 87 (8.05%)	6 / 90 (6.67%)
occurrences all number	75	19	11
Rhinitis
subjects affected / exposed	3 / 284 (1.06%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	3	0	0
Vaginal infection
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Varicella zoster virus infection
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Vestibular neuronitis
subjects affected / exposed	0 / 284 (0.00%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	0	1	0
Viral diarrhoea
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Viral infection
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Viral upper respiratory tract infection
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Vulvovaginal mycotic infection
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Wound infection
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	2	1	0
Vulvovaginal candidiasis
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	2	0	1
Chlamydial infection
subjects affected / exposed	0 / 284 (0.00%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	0	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Dehydration
subjects affected / exposed	4 / 284 (1.41%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	4	0	0
Diabetes mellitus
subjects affected / exposed	32 / 284 (11.27%)	6 / 87 (6.90%)	0 / 90 (0.00%)
occurrences all number	37	7	0
Hyperglycaemia
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Dyslipidaemia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Fluid retention
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Glucose tolerance impaired
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	2 / 90 (2.22%)
occurrences all number	2	0	2
Gout
subjects affected / exposed	12 / 284 (4.23%)	5 / 87 (5.75%)	1 / 90 (1.11%)
occurrences all number	18	5	1
Haemochromatosis
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hypercholesterolaemia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Diabetes mellitus inadequate control
subjects affected / exposed	8 / 284 (2.82%)	6 / 87 (6.90%)	0 / 90 (0.00%)
occurrences all number	9	6	0
Hyperuricaemia
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Hypertriglyceridaemia
subjects affected / exposed	2 / 284 (0.70%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	2	0	0
Hypokalaemia
subjects affected / exposed	3 / 284 (1.06%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	3	2	0
Hypoglycaemia
subjects affected / exposed	2 / 284 (0.70%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	2	2	0
Hypomagnesaemia
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Hyponatraemia
subjects affected / exposed	1 / 284 (0.35%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	1	1	0
Impaired fasting glucose
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	1 / 90 (1.11%)
occurrences all number	1	0	1
Increased appetite
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Type 2 diabetes mellitus
subjects affected / exposed	7 / 284 (2.46%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	7	2	0
Vitamin B12 deficiency
subjects affected / exposed	1 / 284 (0.35%)	0 / 87 (0.00%)	0 / 90 (0.00%)
occurrences all number	1	0	0
Vitamin D deficiency
subjects affected / exposed	3 / 284 (1.06%)	2 / 87 (2.30%)	0 / 90 (0.00%)
occurrences all number	4	2	0
Iron deficiency
subjects affected / exposed	2 / 284 (0.70%)	1 / 87 (1.15%)	0 / 90 (0.00%)
occurrences all number	3	1	0

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Were there any global substantial amendments to the protocol? Yes

26 Apr 2017

Dose was changed from 100mg/0.5mL to 300mg/0.5mL, among other changes.

19 Feb 2018

Name of the active ingredient was changed to inclisiran, among other changes.

15 Mar 2019

Secondary and exploratory endpoints were modified, among other changes.

15 May 2019

Group 1 will receive inclisiran only and Group 2 will receive an active comparator + inclisiran, among other changes.

07 Oct 2020

Sponsor company changed from the Medicines company to Novartis in the protocol, among other changes

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: An open label, active comparator extension trial to assess the effect of long term dosing of inclisiran and evolocumab given as subcutaneous injections in participants with high cardiovascular risk and elevated LDL-C (ORION-3)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage Change in LDL-C from baseline of the ORION-1 Study to Day 210 in ORION-3 (Inclisiran Arm)

Primary: Percentage Change in LDL-C from baseline of the ORION-1 Study to Day 210 in ORION-3 (Inclisiran Arm)

Secondary: Percentage Change in LDL-C from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Percentage Change in LDL-C from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Absolute Change in LDL-C from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Absolute Change in LDL-C from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Percentage Change in PCSK9 levels from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Percentage Change in PCSK9 levels from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Absolute Change in PCSK9 levels from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Absolute Change in PCSK9 levels from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Percentage Change in Triglycerides from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Percentage Change in Triglycerides from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Absolute Change in Triglycerides from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Absolute Change in Triglycerides from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Percentage Change in Apolipoprotein B from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Percentage Change in Apolipoprotein B from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Absolute Change in Apolipoprotein B from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Absolute Change in Apolipoprotein B from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Percentage Change in Lipoprotein-a from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Percentage Change in Lipoprotein-a from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Absolute Change in Lipoprotein-a from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Absolute Change in Lipoprotein-a from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Number of Participants with ≥50% LDL-C Reduction from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Number of Participants with ≥50% LDL-C Reduction from baseline of the ORION-1 study (Inclisiran Arm)

Secondary: Number of Participants Reaching on Treatment LDL-C Levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL (Inclisiran Arm)

Secondary: Number of Participants Reaching on Treatment LDL-C Levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL (Inclisiran Arm)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An open label, active comparator extension trial to assess the effect of long term dosing of inclisiran and evolocumab given as subcutaneous injections in participants with high cardiovascular risk and elevated LDL-C (ORION-3)