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Clinical Trial Results:
An Open-Label Extension Study for Patients With Spinal Muscular Atrophy Who Previously Participated in Investigational Studies of ISIS 396443

Summary
EudraCT number	2015-001870-16
Trial protocol	DE GB SE ES FR BE IT
Global end of trial date	21 Aug 2023

Results information
Results version number	v1(current)
This version publication date	08 Mar 2024
First version publication date	08 Mar 2024
Other versions

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

ISIS 396443-CS11

ISRCTN number

US NCT number

NCT02594124

WHO universal trial number (UTN)

Sponsor organisation name

Biogen

Sponsor organisation address

250 Binney Street, Cambridge, Massachusetts, United States, 02142

Public contact

Study Medical Director, Biogen, clinicaltrials@biogen.com

Scientific contact

Study Medical Director, Biogen, clinicaltrials@biogen.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-001448-PIP01-13

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?

Yes

Analysis stage

Final

Date of interim/final analysis

21 Aug 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

21 Aug 2023

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the trial is to evaluate the long-term safety and tolerability of nusinersen (ISIS 396443) administered by intrathecal (IT) injection to participants with spinal muscular atrophy (SMA) who previously participated in investigational studies of ISIS 396443.

Protection of trial subjects

Written informed consent was obtained from each subject’s parent or legal guardian prior to evaluations being performed for eligibility. Adequate time to review the information in the informed consent and ask questions concerning all portions of the conduct of the study was provided. Through the informed consent process, awareness of the purpose of the study, the procedures, the benefits and risks of the study, the discomforts and the precautions taken was made. Any side effects or other health issues occurring during the study were followed up by the study doctor. Subjects were able to stop taking part in the study at any time without giving any reason.

Background therapy

Evidence for comparator

Actual start date of recruitment

04 Nov 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 177

Country: Number of subjects enrolled

Italy: 25

Country: Number of subjects enrolled

Germany: 23

Country: Number of subjects enrolled

Spain: 15

Country: Number of subjects enrolled

Japan: 11

Country: Number of subjects enrolled

Canada: 8

Country: Number of subjects enrolled

France: 7

Country: Number of subjects enrolled

Korea, Republic of: 5

Country: Number of subjects enrolled

Sweden: 5

Country: Number of subjects enrolled

Türkiye: 5

Country: Number of subjects enrolled

Australia: 4

Country: Number of subjects enrolled

United Kingdom: 3

Country: Number of subjects enrolled

Hong Kong: 3

Country: Number of subjects enrolled

Belgium: 1

Worldwide total number of subjects

292

EEA total number of subjects

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)

187

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants were enrolled at investigative sites in Australia, Belgium, Canada, Germany, Spain, France, United Kingdom, Hong Kong, Italy, Japan, Republic of Korea, Sweden, Turkey, and the United States from 04 November 2015 to 21 August 2023.

Screening details

A total of 292 participants with infantile and later onset spinal muscular atrophy (SMA) who previously participated in ISIS 396443-CS3B[NCT02193074], ISIS 396443-CS4[NCT02292537], ISIS 396443-CS3A[NCT01839656], ISIS 396443-CS12[NCT02052791] and 232SM202[NCT02462759] were enrolled and treated in Modified Maintenance Dosing Regimen (MMDR) period.

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

Infantile SMA Onset CS3A

Arm description

Participants who received nusinersen in study ISIS 396443-CS3A, in an open-label period, received maintenance doses of nusinersen, intrathecal (IT) injection, on days 1, 120, 240, 360, 480, 600, 720, 840, 960, 1080, 1200, 1320, 1440, 1560, and 1680 in MMDR period of this study.

Arm type

Experimental

Investigational medicinal product name

Nusinersen

Investigational medicinal product code

Other name

ISIS 396443

Pharmaceutical forms

Solution for injection

Routes of administration

Intrathecal use

Dosage and administration details

Administered as specified in the treatment arm.

Infantile SMA Onset CS3B Previous Control

Arm description

Participants who received sham procedures in study ISIS 396443-CS3B, in a double-blind period, received 4 loading doses of nusinersen IT injection on Days 1, 15, 29, and 64 followed by maintenance doses of nusinersen IT injection, on days 1, 120, 240, 360, 480, 600, 720, 840, 960, 1080, 1200, 1320, 1440, 1560, and 1680 in MMDR period of this study.

Arm type

Experimental

Investigational medicinal product name

Nusinersen

Investigational medicinal product code

Other name

ISIS 396443

Pharmaceutical forms

Solution for injection

Routes of administration

Intrathecal use

Dosage and administration details

Administered as specified in the treatment arm.

Infantile SMA Onset CS3B Previous ISIS 396443

Arm description

Participants who received nusinersen in study ISIS 396443-CS3B, in the double-blind period, received 3 sham procedures on Days 1, 15, and 64 and 1 loading dose of nusinersen IT injection on Day 29 followed by maintenance doses of nusinersen IT injection, on days 1, 120, 240, 360, 480, 600, 720, 840, 960, 1080, 1200, 1320, 1440, 1560, and 1680 in MMDR period of this study.

Arm type

Experimental

Investigational medicinal product name

Nusinersen

Investigational medicinal product code

Other name

ISIS 396443

Pharmaceutical forms

Solution for injection

Routes of administration

Intrathecal use

Dosage and administration details

Administered as specified in the treatment arm.

Infantile SMA Onset 232SM202

Arm description

Participants who received nusinersen in study 232SM202 (i.e., Part 2) in an open-label period, received maintenance doses of nusinersen IT injection, on days 1, 120, 240, 360, 480, 600, 720, 840, 960, 1080, 1200, 1320, 1440, 1560, and 1680 in MMDR period of this study.

Arm type

Experimental

Investigational medicinal product name

Nusinersen

Investigational medicinal product code

Other name

ISIS 396443

Pharmaceutical forms

Solution for injection

Routes of administration

Intrathecal use

Dosage and administration details

Administered as specified in the treatment arm.

Later SMA Onset CS12 Type 2

Arm description

Participants who received nusinersen in study ISIS 396443-CS12 in an open-label period, received maintenance doses of nusinersen IT injection, on days 1, 120, 240, 360, 480, 600, 720, 840, 960, 1080, 1200, 1320, 1440, 1560, and 1680 in MMDR period of this study.

Arm type

Experimental

Investigational medicinal product name

Nusinersen

Investigational medicinal product code

Other name

ISIS 396443

Pharmaceutical forms

Solution for injection

Routes of administration

Intrathecal use

Dosage and administration details

Administered as specified in the treatment arm.

Later SMA Onset CS12 Type 3

Arm description

Arm type

Experimental

Investigational medicinal product name

Nusinersen

Investigational medicinal product code

Other name

ISIS 396443

Pharmaceutical forms

Solution for injection

Routes of administration

Intrathecal use

Dosage and administration details

Administered as specified in the treatment arm.

Later SMA Onset CS4 Previous Control

Arm description

Participants who received sham procedures in the study ISIS 396443-CS4 in a double-blind period received 3 loading doses of nusinersen administered by IT injection on Days 1, 29, and 85 followed by maintenance doses of nusinersen IT injection, on days 1, 120, 240, 360, 480, 600, 720, 840, 960, 1080, 1200, 1320, 1440, 1560, and 1680 in MMDR period of this study.

Arm type

Experimental

Investigational medicinal product name

Nusinersen

Investigational medicinal product code

Other name

ISIS 396443

Pharmaceutical forms

Solution for injection

Routes of administration

Intrathecal use

Dosage and administration details

Administered as specified in the treatment arm.

Later SMA Onset CS4 Previous ISIS 396443

Arm description

Participants who received nusinersen in the study ISIS 396443-CS4 in a double-blind period received 2 loading doses of nusinersen administered by IT injection on Days 1 and 85 and 1 sham procedure on Day 29 followed by maintenance doses of nusinersen IT injection, on days 1, 120, 240, 360, 480, 600, 720, 840, 960, 1080, 1200, 1320, 1440, 1560, and 1680 in MMDR period of this study.

Arm type

Experimental

Investigational medicinal product name

Nusinersen

Investigational medicinal product code

Other name

ISIS 396443

Pharmaceutical forms

Solution for injection

Routes of administration

Intrathecal use

Dosage and administration details

Administered as specified in the treatment arm.

Later SMA Onset 232SM202

Arm description

Arm type

Experimental

Investigational medicinal product name

Nusinersen

Investigational medicinal product code

Other name

ISIS 396443

Pharmaceutical forms

Solution for injection

Routes of administration

Intrathecal use

Dosage and administration details

Administered as specified in the treatment arm.

Number of subjects in period 1	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Started	13	24	65	12	20	25	42	83	8
Completed	10	10	42	7	12	20	19	44	5
Not completed	3	14	23	5	8	5	23	39	3
Consent withdrawn by subject	2	3	5	1	8	4	13	19	-
Physician decision	-	2	-	-	-	-	-	1	-
Commercial Drug	-	1	6	3	-	-	7	11	2
Adverse event, non-fatal	-	5	8	1	-	-	2	2	-
Reason Not Specified	1	3	4	-	-	1	1	6	1

Baseline characteristics

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Reporting group title

Infantile SMA Onset CS3A

Reporting group description

Reporting group title

Infantile SMA Onset CS3B Previous Control

Reporting group description

Reporting group title

Infantile SMA Onset CS3B Previous ISIS 396443

Reporting group description

Reporting group title

Infantile SMA Onset 232SM202

Reporting group description

Reporting group title

Later SMA Onset CS12 Type 2

Reporting group description

Reporting group title

Later SMA Onset CS12 Type 3

Reporting group description

Reporting group title

Later SMA Onset CS4 Previous Control

Reporting group description

Reporting group title

Later SMA Onset CS4 Previous ISIS 396443

Reporting group description

Reporting group title

Later SMA Onset 232SM202

Reporting group description

Reporting group values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202	Total
Number of subjects	13	24	65	12	20	25	42	83	8	292
Age categorical
Units: Subjects
Infants and toddlers (28 days - 23 months)	0	24	65	0	0	0	0	0	0	89
Children (2 - 11 years)	13	0	0	12	19	10	42	83	8	187
12 - 17 years	0	0	0	0	0	12	0	0	0	12
Adults (18 - 64 years)	0	0	0	0	1	3	0	0	0	4
Gender categorical
Units: Subjects
Male	7	9	29	6	12	10	21	37	5	136
Female	6	15	36	6	8	15	21	46	3	156
Ethnicity
Units: Subjects
Hispanic or Latino	1	3	10	2	2	6	0	4	1	29
Not Hispanic or Latino	12	18	47	7	18	19	37	69	5	232
Not reported	0	3	8	3	0	0	5	10	2	31
Race
Units: Subjects
American Indian or Alaska native	0	0	1	0	0	0	0	0	1	2
Asian	1	1	2	4	1	1	7	16	0	33
Black or African American	0	0	3	0	0	1	1	1	0	6
White	10	18	47	5	18	23	26	53	4	204
Multiple	1	2	1	0	1	0	3	3	0	11
Other	1	0	3	0	0	0	0	0	1	5
Not reported	0	3	8	3	0	0	5	10	2	31

End points

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Reporting group title

Infantile SMA Onset CS3A

Reporting group description

Reporting group title

Infantile SMA Onset CS3B Previous Control

Reporting group description

Reporting group title

Infantile SMA Onset CS3B Previous ISIS 396443

Reporting group description

Reporting group title

Infantile SMA Onset 232SM202

Reporting group description

Reporting group title

Later SMA Onset CS12 Type 2

Reporting group description

Reporting group title

Later SMA Onset CS12 Type 3

Reporting group description

Reporting group title

Later SMA Onset CS4 Previous Control

Reporting group description

Reporting group title

Later SMA Onset CS4 Previous ISIS 396443

Reporting group description

Reporting group title

Later SMA Onset 232SM202

Reporting group description

Primary: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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End point title

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) ^[1]

End point description

AE:unfavorable and unintended sign, symptom, or disease temporally associated with study/use of an investigational drug, whether or not it’s considered related to investigational drug. SAE:AE that in view of either Investigator/Sponsor, meets any of the following criteria: results in death;is life-threatening:i.e.poses risk of death, hospitalization/it’s prolongation;results in a persistent or significant incapacity or substantial disruption of normal life functions;results in congenital anomaly or birth defect in offspring;is an important event in the opinion of Investigator/Sponsor. TEAE:if it was present prior to first dose of nusinersen or first sham procedure in index study and subsequently worsened in severity/was not present prior to first dose of nusinersen or first sham procedure in index study but subsequently appeared. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11.

End point type

Primary

End point timeframe

From Day 1 up to the end of the study (up to 2848 days)

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: Only descriptive analysis was planned for this end point

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	65	12	20	25	42	83	8
Units: participants
AEs	13	24	65	12	20	25	42	80	8
SAEs	11	23	59	9	12	6	26	47	5

No statistical analyses for this end point

Primary: Number of Participants With Clinically Significant Vital Sign Parameters

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End point title

Number of Participants With Clinically Significant Vital Sign Parameters ^[2]

End point description

Clinically significant vital sign assessment included systolic blood pressure (SBP) (<90, >140 and >160 millimeters of mercury (mmHg)), diastolic blood pressure (DBP) (<50, >90 and >100 mmHg), temperature (T) <36 and >38 degrees Celsius (C), and pulse rate (PR) <60 and >100 beats per minute (bpm) and Respiratory rate (RR) <12 and >20 breaths per minute. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis. ‘Number analysed (n)' signifies number of participants evaluable for this outcome measure for each row.

End point type

Primary

End point timeframe

From Day 1 up to the end of the study (up to 2848 days)

Notes
[2] - 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: Only descriptive analysis was planned for this end point

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	64	12	20	25	42	83	8
Units: participants
SBP<90 mmHg (n=13,24,64,12,20,25,42,83,8)	13	21	58	9	13	12	28	67	6
SBP>140 mmHg (n=13,24,64,12,20,25,42,83,8)	0	2	7	1	2	6	3	1	0
SBP>160 mmHg (n=13,24,64,12,20,25,42,83,8)	0	0	1	0	0	0	0	0	0
DBP<50 mmHg (n=13,24,63,12,20,25,42,83,8)	8	18	49	7	12	19	30	62	6
DBP>90 mmHg (n=13,24,63,12,20,25,42,83,8)	2	5	21	2	4	6	8	17	1
DBP>100 mmHg (n=13,24,63,12,20,25,42,83,8)	0	2	4	0	1	1	2	3	0
PR<60 bpm (n=13,24,64,12,20,25,42,83,8)	0	0	2	1	0	9	2	4	0
PR>100 bpm (n=13,24,64,12,20,25,42,83,8)	13	24	64	12	19	16	42	83	8
T>38.0 C (n= 13,24,64,12,20,25,42,83,8)	2	0	12	1	1	4	4	5	1
T<36.0 C (n=13,24,64,12,20,25,42,83,8)	5	19	36	2	6	8	17	32	1
RR<12 breaths/min (n=13,24,64,12,20,25,42,83,8)	0	0	0	0	0	2	0	2	1
RR>20 breaths/min (n=13,24,64,12,20,25,42,83,8)	13	24	64	12	20	25	42	83	8

No statistical analyses for this end point

Primary: Number of Participants With Clinically Significant Change From Baseline in Weight

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End point title

Number of Participants With Clinically Significant Change From Baseline in Weight ^[3]

End point description

Weight changes were assessed for all participants at every onsite visit throughout the study. Weights were categorized into two categories, decrease of >=7% from baseline and increase of >=7% from baseline. Clinical significance of abnormalities in these parameters was determined based on the investigator’s discretion. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Subjects analysed’ signifies number of participants with data available for endpoint analysis.

End point type

Primary

End point timeframe

From Day 1 up to the end of the study (up to 2848 days)

Notes
[3] - 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: Only descriptive analysis was planned for this end point

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	65	12	20	25	42	83	8
Units: participants
Decrease of >=7% from baseline	0	1	5	0	3	5	1	5	0
Increase of >=7% from baseline	13	22	62	12	19	23	42	82	8

No statistical analyses for this end point

Primary: Number of Participants With Clinically Significant Neurological Examination Abnormalities

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End point title

Number of Participants With Clinically Significant Neurological Examination Abnormalities ^[4]

End point description

0 are placeholder numbers, neurological examination Abnormalities will be listed as AEs by the investigator, please see that section.

End point type

Primary

End point timeframe

From Day 1 up to the end of the study (up to 2848 days)

Notes
[4] - 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: Only descriptive analysis was planned for this end point

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	65	12	20	25	42	83	8
Units: participants	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities

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End point title

Number of Participants With Clinically Significant Laboratory Assessment Abnormalities ^[5]

End point description

0 are placeholder numbers, laboratory abnormalities will be listed as AEs by the investigator, please see that section.

End point type

Primary

End point timeframe

From Day 1 up to the end of the study (up to 2848 days)

Notes
[5] - 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: Only descriptive analysis was planned for this end point

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	65	12	20	25	42	83	8
Units: participants	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Number of Participants With Shift From Baseline in Coagulation Parameters

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End point title

Number of Participants With Shift From Baseline in Coagulation Parameters ^[6]

End point description

Activated partial thromboplastin time (aPTT) and international normalized ratio (INR) were evaluated to assess safety. "Shift to low" measured change in normal, high and unknown values of aPTT and INR at baseline to low values postbaseline. “Shift to high” measured change in normal, high and unknown values of aPTT and INR at baseline to high values postbaseline. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. ‘Number analysed (n)' signifies number of participants with data available for analysis at specified timepoint.

End point type

Primary

End point timeframe

From Day 1 up to the end of the study (up to 2848 days)

Notes
[6] - 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: Only descriptive analysis was planned for this end point

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	65	12	20	25	42	83	8
Units: participants
aPTT:Shift to Low (n=13,22,57,11,20,24,42,81,8)	4	6	30	4	1	2	7	17	2
aPTT:Shift to High (n=12,22,57,10,20,24,41,78,8)	7	10	21	4	6	6	15	20	2
INR:Shift to Low (n=13,22,60,12,20,24,42,81,8)	4	1	4	0	0	1	2	3	0
INR:Shift to High (n=13,21,60,12,20,24,42,81,8)	8	1	10	0	5	2	5	11	0

No statistical analyses for this end point

Primary: Number of Participants With Clinically Significant Shifts in 12 Lead Electrocardiogram (ECG) Results

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End point title

Number of Participants With Clinically Significant Shifts in 12 Lead Electrocardiogram (ECG) Results ^[7]

End point description

Clinical significance of abnormalities in these parameters was determined based on investigator's discretion. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11.

End point type

Primary

End point timeframe

From Day 1 up to the end of the study (up to 2848 days)

Notes
[7] - 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: Only descriptive analysis was planned for this end point

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	22	59	12	20	25	42	83	8
Units: participants	2	1	6	1	0	0	1	1	0

No statistical analyses for this end point

Primary: Number of Participants Taking any Concomitant Medication

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End point title

Number of Participants Taking any Concomitant Medication ^[8]

End point description

A concomitant therapy is any non-protocol-specified drug or substance (including over-the-counter medications, herbal medications, and vitamin supplements) administered between the beginning of screening and the last telephone contact or study visit. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11.

End point type

Primary

End point timeframe

From Day 1 up to the end of the study (up to 2848 days)

Notes
[8] - 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: Only descriptive analysis was planned for this end point

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	65	12	20	25	42	83	8
Units: participants	13	24	65	12	20	25	42	83	8

No statistical analyses for this end point

Secondary: Percentage of Participants With <2 Years of Age Who Attained Motor Milestones as Assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE)

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End point title

Percentage of Participants With <2 Years of Age Who Attained Motor Milestones as Assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE) ^[9]

End point description

HINE is evaluated in infants between 2-24 months of age. It's a simple, standardized instrument including 26 items assessing different aspects of neurological examinations, such as cranial nerves, posture, movements, tone, and reflexes. In this study, Module 2 of HINE (HINE-2) was assessed, which evaluates 8 developmental milestones (head control, sitting, voluntary grasp, ability to kick, rolling, crawling, standing, and walking) scored on a 3, 4, or 5-point scale, with 0 indicating inability to perform task and score of 2, 3, or 4 indicating full milestone development. Total score is calculated by summing item scores to give maximum possible score of 26. CS3A and CS3B arm/groups were planned to be analysed in this endpoint. Safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen/underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis.

End point type

Secondary

End point timeframe

Last observed visit

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: CS3A and CS3B arms were planned to be analysed for this end point.

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443
Number of subjects analysed	8	22	62
Units: percentage of participants
number (not applicable)
Head Control:Unable to Maintain Head Upright	13	86	34
Head Control:Wobbles	13	9	18
Head Control:All the Time Maintained Upright	75	5	48
Sitting:Cannot Sit	13	100	39
Sitting:Sits With Support at Hips	13	0	19
Sitting:Props	0	0	8
Sitting:Stable Sit	13	0	19
Sitting:Pivots (Rotates)	63	0	15
Voluntary Grasp:No Grasp	0	14	6
Voluntary Grasp:Uses Whole Hand	0	55	18
Voluntary Grasp:Index Finger&Thumb;Immature Grasp	0	14	21
Voluntary Grasp:Pincer Grasp	100	18	52
Ability to Kick:No Kicking	0	68	18
Ability to Kick:Kick Horizontally Legs do Not Lift	13	32	29
Ability to Kick:Upward (Vertically)	0	0	10
Ability to Kick:Touches Leg	0	0	11
Ability to Kick:Touches Toes	88	0	32
Rolling:No Rolling	25	91	27
Rolling:Rolling to Side	0	9	37
Rolling:Prone to Supine	13	0	5
Rolling:Supine to Prone	63	0	31
Crawling:Does not Lift Head	63	100	81
Crawling:On Elbow	0	0	13
Crawling:On Outstretched Hand	0	0	2
Crawling:Crawling Flat on Abdomen	13	0	3
Crawling:Crawling on Hands and Knees	25	0	2
Standing:Does not Support Weight	38	100	79
Standing:Supports Weight	13	0	11
Standing:Stands With Support	25	0	10
Standing:Stands Unaided	25	0	0
Walking:No Walking	75	100	95
Walking:Bouncing	0	0	0
Walking:Cruising (Walks Holding on)	13	0	5
Walking:Walking Independently	13	0	0

No statistical analyses for this end point

Secondary: Mean Number of new Motor Milestones Achieved as Assessed by World Health Organization (WHO) Criteria

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End point title

Mean Number of new Motor Milestones Achieved as Assessed by World Health Organization (WHO) Criteria

End point description

The WHO motor milestones are a set of six milestones in motor development, all of which would be expected to be attained by 24 months of age in healthy children. The individual milestones are: sitting without support, standing with assistance, hands and knees crawling, walking with assistance, standing alone and walking alone. Mean of number of new milestones achieved was calculated and reported in this outcome measure. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis.

End point type

Secondary

End point timeframe

MMDR Period: At Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	9	10	43	8	12	18	19	45	6
Units: motor milestone
arithmetic mean (standard deviation)	0.4 ( 0.73 )	0.0 ( 0.00 )	0.7 ( 1.15 )	0.0 ( 0.53 )	-0.6 ( 0.79 )	-0.1 ( 0.73 )	-0.1 ( 0.32 )	-0.2 ( 0.60 )	-0.2 ( 0.75 )

No statistical analyses for this end point

Secondary: Number of Participants who Died or met Permanent Ventilation

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End point title

Number of Participants who Died or met Permanent Ventilation

End point description

Permanent ventilation was defined as tracheostomy or >=16 hours of ventilator support per day continuously for >21 days in the absence of an acute reversible event. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11.

End point type

Secondary

End point timeframe

MMDR Period: Up to Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	65	12	20	25	42	83	8
Units: participants	0	4	4	1	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants not Requiring Permanent Ventilation

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End point title

Number of Participants not Requiring Permanent Ventilation

End point description

The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11.

End point type

Secondary

End point timeframe

MMDR Period: Up to Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	65	12	20	25	42	83	8
Units: participants	13	20	61	11	20	25	42	83	8

No statistical analyses for this end point

Secondary: Change From Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale

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End point title

Change From Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale ^[10]

End point description

The CHOP-INTEND test includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0 (worst) to 4 (best). Total scores range from 0 to 64, with higher scores indicating better movement functioning. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number analysed (n)' signifies number of participants with data available for analysis at a specified timepoint. Only CS3A and CS3B arm groups were planned to be analysed for this end point. ‘99999’ signifies that since only one participant was evaluable at Day 2198, standard deviation (SD) was not estimated.

End point type

Secondary

End point timeframe

Baseline, Day 2198

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: CS3A and CS3B arms were planned to be analysed for this end point.

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443
Number of subjects analysed	13	24	65
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n= 13, 24, 65)	47.4 ( 13.09 )	17.3 ( 9.71 )	38.8 ( 9.43 )
Change at Day 2198 (n=1, 10, 29)	-6.0 ( 99999 )	11.5 ( 12.21 )	4.7 ( 14.18 )

No statistical analyses for this end point

Secondary: Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Total Score

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End point title

Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Total Score

End point description

The HFMSE consists of 33 scored activities used to assess motor function in children with SMA. Participants were asked to do a specific activity (such as rolling) and they were then graded on the quality and execution of that movement on a scale of 0=being unable, 1=performed with some compensation, and 2=unaided. The overall score is the sum of the scores for all activities with a maximum achievable score of 66. If 6 or fewer items are missing, then these items were imputed to be 0 when summing all 33 items. Higher scores indicate increased motor function. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Subjects analysed’ signifies number of participants with data available for endpoint analysis. ‘Number analysed (n)' signifies number of participants with data available for analysis at specified timepoint.

End point type

Secondary

End point timeframe

MMDR Period: Baseline, MMDR Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	17	49	12	20	23	42	81	8
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n= 13, 17, 49, 12, 20, 23, 42, 81, 8)	14.5 ( 13.75 )	0.0 ( 0.00 )	7.3 ( 6.88 )	6.8 ( 6.06 )	25.6 ( 14.23 )	53.6 ( 8.24 )	22.1 ( 7.75 )	26.1 ( 10.99 )	24.5 ( 12.64 )
Change at MMDR Day 1800 (n=10,9,3,8,12,17,19,45,6)	3.4 ( 5.93 )	0.4 ( 0.88 )	6.0 ( 9.12 )	-2.3 ( 3.37 )	-7.0 ( 6.03 )	-2.4 ( 3.41 )	-4.7 ( 7.20 )	-6.2 ( 6.36 )	-1.2 ( 9.83 )

No statistical analyses for this end point

Secondary: Change from Baseline in Revised Upper Limb Module (RULM) Total Score

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End point title

Change from Baseline in Revised Upper Limb Module (RULM) Total Score

End point description

RULM Test is used in participants with SMA to assess upper limb functional ability items and has total of 20 items with an entry item that serves as functional class identification and does not contribute to total score. Remaining 19 scorable items reflect different functional domains and graded on 3-point system with score of 0 (unable), 1 (able, with modification), and 2 (able, no difficulty). There is only 1 item that is scored as a can/cannot score, with 1 as the highest score. Scorable items are summed for total score (0-37), higher scores indicating increased upper limb function. Positive change from baseline indicates improvement. Safety analysis set included all participants who were enrolled&received at least 1 dose of nusinersen/underwent sham procedure during CS11. ‘Subjects analysed’ signifies number of participants with data available for endpoint analysis. ‘Number analysed (n)' signifies number of participants with data available for analysis at specified timepoint.

End point type

Secondary

End point timeframe

MMDR Period: Baseline, MMDR Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	11	6	18	11	20	18	42	80	8
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n=11,6,18,11,20,18,42,80,8)	11.8 ( 7.24 )	1.7 ( 1.63 )	10.3 ( 6.05 )	7.6 ( 6.23 )	24.1 ( 6.14 )	35.9 ( 1.91 )	21.1 ( 4.26 )	23.9 ( 5.69 )	21.4 ( 8.60 )
Change at MMDR Day 1800 (n=9,3,12,6,13,9,20,45,6)	9.1 ( 4.70 )	0.7 ( 0.58 )	10.0 ( 5.38 )	3.3 ( 5.01 )	0.4 ( 3.23 )	0.9 ( 1.76 )	2.4 ( 3.97 )	1.2 ( 3.72 )	3.2 ( 2.71 )

No statistical analyses for this end point

Secondary: Change From Baseline in Total Distance Walked Over Time as Assessed by 6-Minute Walk Test (6MWT)

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End point title

Change From Baseline in Total Distance Walked Over Time as Assessed by 6-Minute Walk Test (6MWT) ^[11]

End point description

The 6MWT measures the distance an individual can walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. Only CS12 Type 2 and CS12 Type 3 arms/ groups were planned to be analysed for this end point. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Subjects analysed’ signifies number of participants with data available for endpoint analysis. ‘Number analysed (n)' signifies number of participants with data available for analysis at specified timepoint. 99999’ signifies that since only one participant was evaluable at Day 2670, standard deviation (SD) was not estimated.

End point type

Secondary

End point timeframe

Baseline, Day 2670

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: CS12 Type 2 and CS12 Type 3 arms were planned to be analysed for this end point.

End point values	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3
Number of subjects analysed	1	13
Units: meters
arithmetic mean (standard deviation)	0 ( 99999 )	253.3 ( 182.74 )

No statistical analyses for this end point

Secondary: Number of Participants who Experienced Contracture Assessment

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End point title

Number of Participants who Experienced Contracture Assessment

End point description

Contracture assessment is performed to assess the motor performance in SMA. The number of participants who experienced at least one contracture at any location and severe contractures in any of the five locations (hip flexors, knee flexors, ankle planter flexors, elbow flexors, forearm flexors) are reported in this outcome measure. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis.

End point type

Secondary

End point timeframe

MMDR Period: At MMDR Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	10	10	41	8	13	18	20	45	5
Units: participant
At least one contracture at any location	9	10	36	8	13	8	19	44	5
Severe contractures in any of the five locations	3	3	16	4	6	1	9	16	2

No statistical analyses for this end point

Secondary: Change From Baseline in Compound Muscular Action Potential (CMAP)

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End point title

Change From Baseline in Compound Muscular Action Potential (CMAP)

End point description

CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. Peroneal amplitude (PA) and ulnar amplitude (UA) data is reported in this end point. Score <0 indicated worse response and >0 indicated better response than the normal matched population. Score change <0 indicated worsening and >0 indicated improvement as compared to baseline. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis. ‘Number analysed (n)' signifies number of participants with data available for analysis at specified timepoint.

End point type

Secondary

End point timeframe

MMDR Period: Baseline, MMDR Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	22	60	8	19	22	31	62	6
Units: millivolt (mV)
arithmetic mean (standard deviation)
PA:Baseline (n=13,22,60,8,19,22,31,62,6)	3.02 ( 2.207 )	0.35 ( 0.517 )	1.91 ( 1.367 )	0.94 ( 0.929 )	1.89 ( 1.369 )	2.71 ( 1.318 )	2.00 ( 2.189 )	1.97 ( 1.586 )	1.35 ( 0.948 )
PA:Change at MMDRDay1800 (n=9,5,54,6,7,13,13,28,2)	-0.41 ( 1.290 )	0.10 ( 0.243 )	0.30 ( 1.395 )	0.92 ( 1.901 )	-0.59 ( 1.069 )	-0.08 ( 1.799 )	0.22 ( 4.832 )	-0.28 ( 0.924 )	0.10 ( 1.414 )
UA:Baseline (n=13,12,60,8,20,23,33,62,6)	1.52 ( 1.563 )	0.20 ( 0.205 )	0.85 ( 0.944 )	0.99 ( 0.861 )	2.81 ( 1.723 )	6.76 ( 2.448 )	1.69 ( 1.133 )	2.71 ( 2.161 )	1.25 ( 0.935 )
UA:Change at MMDRDay1800 (n=9,5,35,6,7,14,13,28,2)	0.45 ( 0.837 )	0.20 ( 0.188 )	0.67 ( 1.261 )	0.15 ( 0.436 )	0.04 ( 0.957 )	0.04 ( 1.641 )	0.32 ( 1.127 )	0.52 ( 1.60 )	2.77 ( 2.729 )

No statistical analyses for this end point

Secondary: Change From Baseline in Body Length

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End point title

Change From Baseline in Body Length

End point description

Participants were analyzed for change in growth parameter of body length to evaluate clinical efficacy. The body length was calculated using either World Health Organization (WHO) or Centers for Disease Control and Prevention (CDC) scales. The CDC scale allows to calculate the body length up to 20 years, while the WHO scale allows to calculate it only up to 10 years. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis.

End point type

Secondary

End point timeframe

MMDR Period: Baseline, Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	4	7	14	6	4	1	8	23	2
Units: centimetres
arithmetic mean (standard deviation)	24.2 ( 2.86 )	19.9 ( 6.99 )	29.4 ( 6.38 )	18.8 ( 10.92 )	18.8 ( 8.54 )	23.1 ( 0 )	23.7 ( 7.06 )	24.6 ( 10.60 )	-10.3 ( 57.63 )

No statistical analyses for this end point

Secondary: Change From Baseline in Weight

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End point title

Change From Baseline in Weight

End point description

Participants were analyzed for change in growth parameter of weight to evaluate clinical efficacy. The weight was calculated using either WHO or CDC scales. The CDC scale allows to calculate the weight up to 20 years, while the WHO scale allows to calculate it only up to 10 years. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis.

End point type

Secondary

End point timeframe

MMDR Period: Baseline, Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	9	11	43	8	13	20	20	50	6
Units: kilograms (kg)
arithmetic mean (standard deviation)	9.8 ( 3.48 )	7.7 ( 4.39 )	9.3 ( 3.25 )	9.5 ( 7.04 )	15.1 ( 5.96 )	13.8 ( 14.88 )	15.4 ( 8.05 )	15.2 ( 7.38 )	11.7 ( 8.09 )

No statistical analyses for this end point

Secondary: Change From Baseline in Weight for Age Percentile

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End point title

Change From Baseline in Weight for Age Percentile

End point description

Participants who were below the age of 36 months were analyzed for change in growth parameter of weight for age to evaluate clinical efficacy. The weight for age percentile was calculated using either WHO or CDC scales. The CDC scale allows to calculate the weight for age percentile up to 20 years, while the WHO scale allows to calculate it only up to 10 years. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis.

End point type

Secondary

End point timeframe

MMDR Period: Baseline, Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	8	11	43	6	0 ^[12]	0 ^[13]	9	14	6
Units: Percentile
arithmetic mean (standard deviation)	5.7 ( 27.30 )	-5.3 ( 28.97 )	0.3 ( 28.55 )	-0.7 ( 25.32 )	( )	( )	0.9 ( 17.22 )	20.2 ( 28.15 )	4.0 ( 33.11 )

Notes
[12] - None of the participants were below the age of 36 months.
[13] - None of the participants were below the age of 36 months.

No statistical analyses for this end point

Secondary: Percentage of CMAP Responders

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End point title

Percentage of CMAP Responders

End point description

CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. A participant was defined as a responder if they had a peroneal amplitude ≥1 mV at last visit (including the amplitude ≥1 mV at baseline and also demonstrated as such at last visit). The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis.

End point type

Secondary

End point timeframe

MMDR Period: At Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	22	60	12	20	24	42	81	8
Units: percentage of responders
number (not applicable)	85	0	72	33	65	67	60	51	25

No statistical analyses for this end point

Secondary: Number of Participants who Achieved Motor Milestones

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End point title

Number of Participants who Achieved Motor Milestones

End point description

Motor milestones were measured based on WHO criteria. The WHO motor milestones are a set of six milestones in motor development, all of which would be expected to be attained by 24 months of age in healthy children. The individual milestones are: sitting without support (SWS), standing with assistance (SWA), hands and knees crawling (HKC), and walking alone (WA). The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis.

End point type

Secondary

End point timeframe

MMDR Period: up to Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	12	22	60	12	20	24	42	81	8
Units: participants
SWS:Achieved at Baseline&Maintained to Last Visit	5	0	16	3	13	23	27	58	5
SWS:Inability at Baseline, Achieved at Last visit	3	0	11	0	0	0	0	0	0
HKC:Achieved at Baseline&Maintained to Last Visit	1	0	0	0	4	20	3	18	2
HKC: Inability at Baseline, Achieved at Last Visit	0	0	4	0	0	1	1	2	1
SWA:Achieved at Baseline&Maintained to Last Visit	1	0	4	0	1	20	3	3	1
SWA:Inability at Baseline, Achieved at Last Visit	0	0	3	0	0	0	0	0	0
WA:Achieved at Baseline&Maintained to Last Visit	1	0	0	0	1	16	1	2	1
WA:Inability at Baseline, Achieved at Last Visit	0	0	1	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants who Achieved Standing Alone and Walking With Assistance

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End point title

Number of Participants who Achieved Standing Alone and Walking With Assistance

End point description

Motor milestones were measured based on WHO criteria. The WHO motor milestones are a set of six milestones in motor development, all of which would be expected to be attained by 24 months of age in healthy children. The individual milestones are: sitting without support, standing with assistance, hands and knees crawling, walking with assistance, standing alone and walking alone. Standing alone and walking with assistance was assessed in this outcome measure. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis.

End point type

Secondary

End point timeframe

MMDR Period: up to Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	12	22	60	12	20	24	42	81	8
Units: participants
Standing alone	1	0	0	0	1	21	2	3	3
Walking with assistance	2	0	3	0	3	21	3	7	1

No statistical analyses for this end point

Secondary: Total Number of Hospitalizations due to Serious Respiratory Events

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End point title

Total Number of Hospitalizations due to Serious Respiratory Events

End point description

Total number of hospitalizations is total number of serious events that occurred during study for all participants under each group. For a participant with multiple SAEs which started at the same date and led to hospitalization, it is counted as one hospitalization. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis. ‘Number analysed (n)' signifies number of participants with data available for analysis at specified timepoint.

End point type

Secondary

End point timeframe

Up to day 2520

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	64	12	20	25	42	83	8
Units: number of hospitalizations
number (not applicable)
Day 1-360 (n=13,24,64,12,20,25,42,83,8)	2	12	30	2	0	0	2	0	0
Day 361-720 (n=13,22,61,12,20,25,42,83,8)	2	1	18	1	1	0	2	1	0
Day 721-1080 (n=12,22,60,12,19,24,42,81,8)	0	15	12	0	0	0	1	2	0
Day 1081-1440 (n=12,21,59,11,18,23,39,78,8)	1	0	4	1	1	0	1	1	0
Day 1441-1800 (n=12,18,55,10,18,23,38,76,7)	2	2	2	2	0	0	0	3	0
Day 1801-2160 (n=12,16,52,6,18,23,32,71,1)	1	1	7	0	0	0	0	1	0
Day 2161-2520 (n= 13,10,39,0,12,20,18,48,0)	0	0	1	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Total Number of Hospitalizations Due to Serious Adverse Events

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End point title

Total Number of Hospitalizations Due to Serious Adverse Events

End point description

End point type

Secondary

End point timeframe

Up to day 2520

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	65	12	20	25	42	83	8
Units: number of hospitalizations
number (not applicable)
Day 1-360 (n=13,24,65,12,20,25,42,83,8)	6	26	89	12	2	0	10	8	3
Day 361-720 (n=13,22,61,12,20,25,42,83,8)	6	19	64	4	7	2	10	12	2
Day 721-1080 (n=12,22,60,12,19,24,42,81,8)	5	29	63	7	2	0	21	21	1
Day 1081-1440 (n=12,21,59,11,18,23,39,78,8)	2	10	36	4	5	1	6	10	3
Day 1441-1800 (n=12,18,55,10,18,23,38,76,7)	4	10	19	3	3	0	5	18	0
Day 1801-2160 (n=12,16,52,6,18,23,32,71,1)	1	8	32	0	2	2	6	13	0
Day 2161-2520 (n=13,10,39,0,12,20,18,48,0)	0	1	14	0	0	0	1	2	0

No statistical analyses for this end point

Secondary: Percent of Time in Hospitalization

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End point title

Percent of Time in Hospitalization

End point description

The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis. ‘Number analysed (n)' signifies number of participants with data available for analysis at specified timepoint.

End point type

Secondary

End point timeframe

Up to Day 2160

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	22	60	12	20	24	42	81	8
Units: Percent of time (in Days)
median (full range (min-max))
Day 1-360 (n=13,22,60,12,20,24,42,81,8)	0.00 (0.00 to 0.2)	1.11 (0.00 to 16.7)	0.28 (0.00 to 22.8)	0.28 (0.00 to 11.4)	0.00 (0.00 to 2.5)	0.00 (0.00 to 0.8)	0.00 (0.00 to 4.4)	0.00 (0.00 to 6.4)	0.00 (0.00 to 2.8)
Day 361-720 (n=12,22,60,12,18,24,42,80,8)	0.28 (0.00 to 4.7)	2.08 (0.00 to 17.2)	0.56 (0.00 to 19.2)	0.00 (0.00 to 7.8)	0.00 (0.00 to 3.1)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 29.7)	0.00 (0.00 to 2.5)
Day 721-1080 (n=12,20,59,12,18,23,39,78,8)	0.00 (0.00 to 1.7)	0.00 (0.00 to 7.5)	0.00 (0.00 to 31.3)	0.00 (0.00 to 20.3)	0.00 (0.00 to 6.1)	0.00 (0.00 to 1.4)	0.00 (0.00 to 1.4)	0.00 (0.00 to 12.2)	0.00 (0.00 to 11.4)
Day 1081-1440 (n=12,17,54,11,18,23,36,75,8)	0.00 (0.00 to 0.8)	0.00 (0.00 to 7.5)	0.00 (0.00 to 9.7)	0.00 (0.00 to 48.6)	0.00 (0.00 to 1.9)	0.00 (0.00 to 0.8)	0.00 (0.00 to 5.8)	0.00 (0.00 to 35.3)	0.69 (0.00 to 1.9)
Day 1441-1800 (n=12,15,50,10,17,23,33,80,7)	0.00 (0.00 to 8.3)	0.00 (0.00 to 20.2)	0.00 (0.00 to 22.6)	0.00 (0.00 to 12.1)	0.00 (0.00 to 2.0)	0.00 (0.00 to 0.8)	0.00 (0.00 to 5.3)	0.00 (0.00 to 8.9)	0.00 (0.00 to 1.7)
Day 1801-2160 (n=7,8,19,6,10,18,9,31,1)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)

No statistical analyses for this end point

Secondary: Change From Baseline in Cobb-Angle on X-Ray of the Thoracolumbar Spine

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End point title

Change From Baseline in Cobb-Angle on X-Ray of the Thoracolumbar Spine

End point description

Cobb angle is a measurement of the degree of side-to-side spinal curvature used to define scoliosis. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis. ‘Number analysed (n)' signifies number of participants with data available for analysis at specified timepoint.

End point type

Secondary

End point timeframe

Baseline, MMDR Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	8	11	42	8	12	10	35	67	5
Units: degrees
arithmetic mean (standard deviation)
BL, n= 8,11,42,8,12,10,35,67,5	22.7 ( 17.86 )	16.6 ( 13.38 )	34.8 ( 18.43 )	49.2 ( 13.19 )	38.5 ( 27.36 )	29.8 ( 24.09 )	24.3 ( 19.08 )	26.8 ( 20.33 )	33.0 ( 16.94 )
Change from BL :MMDRday1800,n=4,4,26,5,4,7,15,30,1	29.8 ( 9.46 )	16.9 ( 27.27 )	13.0 ( 29.91 )	-11.6 ( 24.65 )	-3.8 ( 17.01 )	4.0 ( 7.78 )	19.8 ( 30.83 )	18.8 ( 30.30 )	-13.8 ( 0 )

No statistical analyses for this end point

Secondary: Pediatric Quality of Life Inventory (PedsQL) Questionnaires Total Score by Domain

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End point title

Pediatric Quality of Life Inventory (PedsQL) Questionnaires Total Score by Domain

End point description

The PedsQL parent (P) and self (S) reported questionnaire is collected for children and teenagers in the following age categories: 2-4, 5-7, 8-12 and 13-18. Four dimensions are collected: Physical, Emotional, Social and School functioning and each item is scored on a 5 point ordinal scale (0= Never, 1 = Almost Never, 2= Sometimes, 3 = Often, 4 = Almost Always). The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis. ‘Number analysed (n)' signifies number of participants with data available for analysis at specified timepoint.

End point type

Secondary

End point timeframe

MMDR Period: At Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	8	6	28	7	8	11	20	50	5
Units: score on scale
arithmetic mean (standard deviation)
S:Physical Functioning(n=8,6,28,7,8,11,20,50,5)	37.1 ( 11.26 )	22.4 ( 31.52 )	47.5 ( 25.31 )	32.6 ( 20.48 )	39.8 ( 14.54 )	52.6 ( 21.28 )	45.4 ( 13.85 )	39.7 ( 17.97 )	53.7 ( 24.46 )
S:Emotional Functioning(n=8,6,29,7,8,11,20,50,5)	61.9 ( 12.52 )	61.7 ( 26.39 )	63.3 ( 20.71 )	67.4 ( 19.55 )	76.3 ( 15.29 )	80.0 ( 18.97 )	84.6 ( 15.42 )	74.5 ( 22.80 )	67.0 ( 16.43 )
S:Social Functioning(n=8,6,28,7,8,11,20,50,7)	67.5 ( 22.83 )	50.8 ( 41.52 )	67.1 ( 22.87 )	75.7 ( 20.09 )	76.3 ( 10.94 )	81.4 ( 10.27 )	83.3 ( 15.07 )	76.3 ( 13.88 )	80.0 ( 12.25 )
S:School/Work Functioning(n=8,6,28,5,8,11,20,50,5)	54.4 ( 14.25 )	40.8 ( 33.23 )	66.1 ( 17.66 )	71.4 ( 14.64 )	75.6 ( 9.43 )	76.4 ( 15.83 )	81.8 ( 14.89 )	77.1 ( 15.22 )	82.0 ( 11.51 )
P:Physical Functioning(n=8,10,42,7,8,9,20,49,6)	25.0 ( 27.55 )	19.1 ( 24.54 )	24.9 ( 22.77 )	32.6 ( 30.07 )	29.3 ( 16.45 )	46.2 ( 76.78 )	35.2 ( 18.19 )	33.5 ( 18.41 )	20.8 ( 5.82 )
P:Emotional Functioning(n=8,10,42,7,8,9,20,49,6)	68.1 ( 13.08 )	69.5 ( 17.23 )	58.7 ( 14.90 )	65.0 ( 26.46 )	70.0 ( 19.46 )	74.4 ( 22.70 )	78.0 ( 18.74 )	78.2 ( 19.60 )	74.2 ( 11.14 )
P:Social Functioning(n=8,10,42,7,8,9,20,49,6)	47.5 ( 12.82 )	50.0 ( 23.66 )	51.3 ( 20.06 )	64.3 ( 22.63 )	64.4 ( 25.70 )	72.2 ( 18.05 )	70.0 ( 20.67 )	71.0 ( 17.50 )	60.8 ( 13.20 )
P:School/Work Functioning(n=8,11,42,7,8,9,20,49,5)	48.8 ( 12.17 )	48.5 ( 31.23 )	51.4 ( 21.36 )	63.6 ( 18.64 )	76.3 ( 10.94 )	77.8 ( 20.78 )	78.8 ( 20.19 )	78.0 ( 14.75 )	79.2 ( 9.70 )

No statistical analyses for this end point

Secondary: Change From Baseline in Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) Questionnaire Total Score

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End point title

Change From Baseline in Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) Questionnaire Total Score

End point description

The ACEND is a questionnaire that includes a total of seven domains assessing physical impact (including feeding/grooming/dressing, sitting/play, transfers, and mobility) and general caregiver impact (including time, emotion, and finance) and each domain comprises several items. The total score (TS) for each domain will be calculated on a scale of 0 to 100. Higher scores indicate a greater impact on the caregiver. The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11. Here, ‘Number of subjects analysed’ signifies number of participants with data available for endpoint analysis.

End point type

Secondary

End point timeframe

MMDR Period: Baseline, MMDR Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	10	11	38	8	8	9	18	47	6
Units: score on scale
arithmetic mean (standard deviation)
Feeding/Grooming/Dressing TS:Change MMDRDay1800	14.2 ( 21.56 )	0.6 ( 2.01 )	18.5 ( 22.07 )	9.2 ( 15.91 )	8.3 ( 11.55 )	-0.4 ( 1.11 )	4.6 ( 18.90 )	5.9 ( 12.07 )	2.8 ( 7.72 )
Sitting/Play TS: Change at MMDR Day 1800	0.8 ( 10.29 )	-0.4 ( 14.91 )	5.5 ( 28.01 )	1.5 ( 22.21 )	1.0 ( 8.21 )	0.0 ( 0.00 )	-1.8 ( 16.48 )	1.7 ( 16.08 )	-2.0 ( 4.90 )
Transfers TS: Change at MMDR Day 1800	0.4 ( 7.24 )	0.7 ( 1.62 )	0.0 ( 12.32 )	-5.5 ( 6.68 )	-6.4 ( 10.98 )	0.4 ( 3.71 )	-3.6 ( 16.17 )	1.2 ( 18.16 )	-4.0 ( 11.03 )
Mobility TS: Change at MMDR Day 1800	-2.3 ( 14.93 )	0.5 ( 1.72 )	7.5 ( 22.52 )	-12.1 ( 18.69 )	-9.6 ( 12.49 )	-2.5 ( 6.14 )	1.9 ( 18.47 )	-5.8 ( 17.50 )	6.7 ( 20.66 )
Time TS: Change at MMDR Day 1800	4.4 ( 19.78 )	6.8 ( 24.76 )	-0.7 ( 22.60 )	-6.3 ( 21.65 )	-1.6 ( 21.33 )	-2.1 ( 12.10 )	1.4 ( 17.22 )	0.5 ( 16.78 )	-6.3 ( 14.25 )
Emotion TS: Change at MMDR Day 1800	5.0 ( 14.80 )	6.3 ( 15.82 )	-2.1 ( 20.98 )	2.1 ( 14.22 )	-2.8 ( 26.23 )	1.2 ( 12.96 )	4.7 ( 12.73 )	-2.5 ( 12.70 )	-18.1 ( 12.01 )
Finance TS: Change at MMDR Day 1800	-1.0 ( 17.29 )	7.3 ( 20.66 )	-4.1 ( 22.17 )	4.4 ( 18.98 )	1.9 ( 24.49 )	1.1 ( 8.94 )	7.2 ( 17.92 )	2.1 ( 19.94 )	-3.3 ( 8.16 )

No statistical analyses for this end point

Secondary: Number of Participants With Disease-related Hospitalizations and AEs

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End point title

Number of Participants With Disease-related Hospitalizations and AEs

End point description

The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11.

End point type

Secondary

End point timeframe

MMDR Period: up to Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	65	12	20	25	42	83	8
Units: participants
Disease-related hospitalization	6	9	27	5	9	0	13	23	1
Disease-related AEs	11	21	60	7	16	12	36	68	8

No statistical analyses for this end point

Secondary: Survival Rate

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End point title

Survival Rate

End point description

All dosed population included all participants who received a dose of nusinersen or were in the sham treatment group.

End point type

Secondary

End point timeframe

MMDR Period: up to Day 1800

End point values	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset CS12 Type 2	Later SMA Onset CS12 Type 3	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443	Later SMA Onset 232SM202
Number of subjects analysed	13	24	65	12	20	25	42	83	8
Units: percentage of participants
number (not applicable)	100	79.17	87.69	11	20	25	97.62	98.8	8

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Day 1 up to the end of the study (up to 2848 days)

Adverse event reporting additional description

The safety analysis set included all participants who were enrolled and received at least 1 dose of nusinersen or underwent sham procedure during CS11.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

Infantile SMA Onset CS3A

Reporting group description

Reporting group title

Infantile SMA Onset CS3B Previous Control

Reporting group description

Reporting group title

Infantile SMA Onset CS3B Previous ISIS 396443

Reporting group description

Reporting group title

Infantile SMA Onset 232SM202

Reporting group description

Reporting group title

Later SMA Onset 232SM202

Reporting group description

Reporting group title

Later SMA Onset CS12 Type 3

Reporting group description

Reporting group title

Later SMA Onset CS12 Type 2

Reporting group description

Reporting group title

Later SMA Onset CS4 Previous Control

Reporting group description

Reporting group title

Later SMA Onset CS4 Previous ISIS 396443

Reporting group description

Serious adverse events	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset 232SM202	Later SMA Onset CS12 Type 3	Later SMA Onset CS12 Type 2	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443
Total subjects affected by serious adverse events
subjects affected / exposed	11 / 13 (84.62%)	23 / 24 (95.83%)	59 / 65 (90.77%)	9 / 12 (75.00%)	5 / 8 (62.50%)	6 / 25 (24.00%)	12 / 20 (60.00%)	26 / 42 (61.90%)	47 / 83 (56.63%)
number of deaths (all causes)	0	5	8	1	0	0	0	1	1
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain stem glioma
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hair follicle tumour benign
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypotension
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypovolaemic shock
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Positive airway pressure therapy
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Complication of device insertion
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Complication associated with device
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Impaired healing
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Medical device discomfort
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Generalised oedema
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Discomfort
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sudden death
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Cytokine storm
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anaphylactic reaction
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Testicular torsion
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Acute respiratory failure
subjects affected / exposed	3 / 13 (23.08%)	9 / 24 (37.50%)	15 / 65 (23.08%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 25 (0.00%)	2 / 20 (10.00%)	3 / 42 (7.14%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 3	0 / 26	0 / 29	0 / 4	0 / 0	0 / 0	0 / 2	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Adenoidal hypertrophy
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Apnoea
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aspiration
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	5 / 65 (7.69%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 5	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchial hyperreactivity
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic respiratory failure
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchial secretion retention
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obstructive airways disorder
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obstructive sleep apnoea syndrome
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory arrest
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	2 / 13 (15.38%)	5 / 24 (20.83%)	9 / 65 (13.85%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 2	0 / 7	0 / 11	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 13 (0.00%)	3 / 24 (12.50%)	9 / 65 (13.85%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 10	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory symptom
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sputum increased
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tachypnoea
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract inflammation
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
Device malfunction
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device mechanical issue
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device failure
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood culture positive
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterovirus test positive
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronavirus test positive
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Human rhinovirus test positive
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory rate increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oxygen saturation decreased
subjects affected / exposed	0 / 13 (0.00%)	4 / 24 (16.67%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 5	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus test positive
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rubulavirus test positive
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Accident
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Face injury
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	3 / 83 (3.61%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 1	0 / 1	0 / 0	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	1 / 65 (1.54%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	3 / 83 (3.61%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foreign body aspiration
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrostomy tube site complication
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal stoma complication
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal procedural complication
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foreign body in respiratory tract
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Joint dislocation
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Limb injury
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal procedural complication
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neurological procedural complication
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post lumbar puncture syndrome
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	4 / 83 (4.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural complication
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Postoperative ileus
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Procedural pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Procedural dizziness
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract procedural complication
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Unintentional medical device removal
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound dehiscence
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Cryptorchism
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal muscular atrophy
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Laryngeal cleft
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Developmental hip dysplasia
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Talipes
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac arrest
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardio-respiratory arrest
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Supraventricular extrasystoles
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wolff-parkinson-white syndrome
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Altered state of consciousness
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Status epilepticus
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxic-ischaemic encephalopathy
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Brain hypoxia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis ulcerative
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acetonaemic vomiting
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dental caries
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cyclic vomiting syndrome
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Faecaloma
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis haemorrhagic
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gingival hypertrophy
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hiatus hernia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subileus
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	5 / 65 (7.69%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 6	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rash papular
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematuria
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthralgia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foot deformity
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	3 / 83 (3.61%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hip deformity
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pathological fracture
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neuromuscular scoliosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Kyphoscoliosis
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 5	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Joint contracture
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Retrognathia
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Scoliosis
subjects affected / exposed	2 / 13 (15.38%)	0 / 24 (0.00%)	10 / 65 (15.38%)	3 / 12 (25.00%)	2 / 8 (25.00%)	0 / 25 (0.00%)	6 / 20 (30.00%)	11 / 42 (26.19%)	22 / 83 (26.51%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 11	0 / 3	0 / 2	0 / 0	0 / 6	0 / 11	0 / 22
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abdominal sepsis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute sinusitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Adenovirus infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis perforated
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis staphylococcal
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis pneumococcal
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 6	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronavirus infection
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronavirus pneumonia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Covid-19
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Covid-19 pneumonia
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterovirus infection
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	6 / 65 (9.23%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	3 / 42 (7.14%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 8	0 / 1	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 5	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis viral
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis adenovirus
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Human bocavirus infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemophilus infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Incision site abscess
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal sepsis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	3 / 83 (3.61%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Laryngitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection viral
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	7 / 65 (10.77%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 16	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nasopharyngitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metapneumovirus infection
subjects affected / exposed	1 / 13 (7.69%)	2 / 24 (8.33%)	4 / 65 (6.15%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 4	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Medical device site abscess
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis chronic
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media acute
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media chronic
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Parainfluenzae virus infection
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	6 / 65 (9.23%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 9	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Periorbital cellulitis
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumococcal bacteraemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngotonsillitis
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis streptococcal
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	3 / 13 (23.08%)	8 / 24 (33.33%)	27 / 65 (41.54%)	5 / 12 (41.67%)	1 / 8 (12.50%)	0 / 25 (0.00%)	2 / 20 (10.00%)	8 / 42 (19.05%)	6 / 83 (7.23%)
occurrences causally related to treatment / all	0 / 5	0 / 15	0 / 44	0 / 5	0 / 1	0 / 0	0 / 2	0 / 12	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	6 / 65 (9.23%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 9	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	4 / 65 (6.15%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 4	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia haemophilus
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia influenzal
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia moraxella
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia mycoplasmal
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia parainfluenzae viral
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia serratia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia respiratory syncytial viral
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia pseudomonal
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia streptococcal
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pseudomonas bronchitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	12 / 65 (18.46%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	4 / 42 (9.52%)	3 / 83 (3.61%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 13	0 / 1	0 / 0	0 / 0	0 / 0	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pseudomonas infection
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 6	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulpitis dental
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyuria
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	8 / 65 (12.31%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 17	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection viral
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rhinovirus infection
subjects affected / exposed	0 / 13 (0.00%)	5 / 24 (20.83%)	5 / 65 (7.69%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	2 / 42 (4.76%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 5	0 / 12	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rotavirus infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stenotrophomonas infection
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stoma site infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tracheitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 13 (0.00%)	3 / 24 (12.50%)	5 / 65 (7.69%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 7	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral pericarditis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Varicella
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	2 / 13 (15.38%)	1 / 24 (4.17%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	3 / 65 (4.62%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 3	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Feeding intolerance
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malnutrition
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ketoacidosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	0 / 83 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Infantile SMA Onset CS3A	Infantile SMA Onset CS3B Previous Control	Infantile SMA Onset CS3B Previous ISIS 396443	Infantile SMA Onset 232SM202	Later SMA Onset 232SM202	Later SMA Onset CS12 Type 3	Later SMA Onset CS12 Type 2	Later SMA Onset CS4 Previous Control	Later SMA Onset CS4 Previous ISIS 396443
Total subjects affected by non serious adverse events
subjects affected / exposed	13 / 13 (100.00%)	23 / 24 (95.83%)	65 / 65 (100.00%)	12 / 12 (100.00%)	8 / 8 (100.00%)	25 / 25 (100.00%)	20 / 20 (100.00%)	40 / 42 (95.24%)	79 / 83 (95.18%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	0	0	0	0	0	2	0	1	1
Hair follicle tumour benign
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	1	0	0	0	0	0	0	0	2
Vascular disorders
Hypertension
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	1	3	0	0	0	0	0
Hypotension
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	0	0	3	1	0	0	1	1	1
General disorders and administration site conditions
Fatigue
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	5 / 65 (7.69%)	3 / 12 (25.00%)	0 / 8 (0.00%)	3 / 25 (12.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	2	5	3	0	4	0	0	1
Developmental delay
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	4	0	0	0	0	0	0
Gait disturbance
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	3 / 25 (12.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0	0
Infusion site bruising
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Medical device site haemorrhage
subjects affected / exposed	2 / 13 (15.38%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Peripheral swelling
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	1	0	2	0	0	2	0	1	2
Pneumatosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Pyrexia
subjects affected / exposed	13 / 13 (100.00%)	15 / 24 (62.50%)	50 / 65 (76.92%)	5 / 12 (41.67%)	5 / 8 (62.50%)	3 / 25 (12.00%)	10 / 20 (50.00%)	21 / 42 (50.00%)	39 / 83 (46.99%)
occurrences all number	66	76	252	15	6	5	21	55	117
Pain
subjects affected / exposed	2 / 13 (15.38%)	3 / 24 (12.50%)	3 / 65 (4.62%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	2	3	3	0	1	0	0	1	2
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	0	2	1	0	0	0	1	1	2
Multiple allergies
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	0	0	2	0	0	0	1
Seasonal allergy
subjects affected / exposed	0 / 13 (0.00%)	3 / 24 (12.50%)	9 / 65 (13.85%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	1 / 20 (5.00%)	3 / 42 (7.14%)	5 / 83 (6.02%)
occurrences all number	0	5	9	0	0	2	1	3	6
Reproductive system and breast disorders
Heavy menstrual bleeding
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0
Testicular atrophy
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	4 / 65 (6.15%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	1	2	4	1	0	0	0	0	2
Adenoidal hypertrophy
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	1	0	5	0	0	0	1	0	1
Aspiration
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	5 / 65 (7.69%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	1	7	1	0	0	0	0	0
Asthma
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	3 / 42 (7.14%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	1	0	3	0
Atelectasis
subjects affected / exposed	5 / 13 (38.46%)	2 / 24 (8.33%)	9 / 65 (13.85%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences all number	6	2	12	1	0	0	0	0	3
Bronchial wall thickening
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Chronic respiratory failure
subjects affected / exposed	0 / 13 (0.00%)	3 / 24 (12.50%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	3	0	0	0	0	0	0	0
Epiglottic oedema
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Emphysema
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Dyspnoea
subjects affected / exposed	1 / 13 (7.69%)	2 / 24 (8.33%)	3 / 65 (4.62%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	1	2	4	3	0	0	0	0	1
Cough
subjects affected / exposed	4 / 13 (30.77%)	4 / 24 (16.67%)	16 / 65 (24.62%)	5 / 12 (41.67%)	5 / 8 (62.50%)	2 / 25 (8.00%)	6 / 20 (30.00%)	15 / 42 (35.71%)	29 / 83 (34.94%)
occurrences all number	15	5	30	7	8	3	7	33	62
Epistaxis
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	11 / 65 (16.92%)	0 / 12 (0.00%)	0 / 8 (0.00%)	3 / 25 (12.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	1	1	14	0	0	4	0	1	3
Increased viscosity of upper respiratory secretion
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	2	0	0	0	0	0	0
Increased upper airway secretion
subjects affected / exposed	0 / 13 (0.00%)	3 / 24 (12.50%)	6 / 65 (9.23%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	5	8	0	0	0	0	0	1
Increased bronchial secretion
subjects affected / exposed	2 / 13 (15.38%)	4 / 24 (16.67%)	8 / 65 (12.31%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	2	4	13	0	0	0	0	0	1
Hypoxia
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences all number	1	1	5	0	0	0	1	0	2
Laryngospasm
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	0	0	0	0	1	0	1
Lower respiratory tract congestion
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	5	0	0	0	0	0	1
Lung infiltration
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	1	1	1	0	0	0	0	0	1
Nasal congestion
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	6 / 65 (9.23%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	9 / 83 (10.84%)
occurrences all number	1	0	11	4	0	0	1	3	12
Pleural effusion
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	0 / 65 (0.00%)	3 / 12 (25.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	1	1	0	3	0	0	0	1	1
Obstructive sleep apnoea syndrome
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	2 / 20 (10.00%)	4 / 42 (9.52%)	5 / 83 (6.02%)
occurrences all number	0	0	2	0	0	0	2	5	5
Obstructive airways disorder
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0
Noninfective bronchitis
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	3 / 65 (4.62%)	1 / 12 (8.33%)	1 / 8 (12.50%)	3 / 25 (12.00%)	4 / 20 (20.00%)	8 / 42 (19.05%)	12 / 83 (14.46%)
occurrences all number	1	1	4	2	1	3	5	9	27
Respiratory disorder
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	3 / 65 (4.62%)	1 / 12 (8.33%)	1 / 8 (12.50%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	1	0	4	1	1	1	0	0	2
Rales
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Pulmonary oedema
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0
Productive cough
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	2 / 42 (4.76%)	5 / 83 (6.02%)
occurrences all number	0	0	3	0	0	0	1	3	8
Respiratory distress
subjects affected / exposed	1 / 13 (7.69%)	5 / 24 (20.83%)	5 / 65 (7.69%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	1	8	6	1	0	0	0	0	1
Rhinorrhoea
subjects affected / exposed	2 / 13 (15.38%)	2 / 24 (8.33%)	7 / 65 (10.77%)	1 / 12 (8.33%)	2 / 8 (25.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	4 / 42 (9.52%)	8 / 83 (9.64%)
occurrences all number	3	2	10	1	2	1	1	7	13
Rhinitis allergic
subjects affected / exposed	0 / 13 (0.00%)	3 / 24 (12.50%)	1 / 65 (1.54%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	3 / 42 (7.14%)	0 / 83 (0.00%)
occurrences all number	0	3	1	0	1	0	0	4	0
Restrictive pulmonary disease
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	0	1	1	0	0	0	1	1	2
Tonsillar hypertrophy
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	3 / 83 (3.61%)
occurrences all number	0	0	6	0	0	1	0	1	3
Tachypnoea
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	2	1	0	0	0	0	0
Sputum discoloured
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0	0
Sleep apnoea syndrome
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	3 / 42 (7.14%)	1 / 83 (1.20%)
occurrences all number	0	0	0	0	0	0	0	3	1
Wheezing
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	1 / 83 (1.20%)
occurrences all number	0	2	1	0	0	0	0	2	1
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	2 / 12 (16.67%)	0 / 8 (0.00%)	3 / 25 (12.00%)	3 / 20 (15.00%)	1 / 42 (2.38%)	4 / 83 (4.82%)
occurrences all number	0	0	2	2	0	3	3	3	4
Agitation
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	1	1	1	0	0	0	0	1	0
Anxiety disorder
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Attention deficit hyperactivity disorder
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	1	1	1	0	0	1	0	1	1
Panic attack
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0
Mental status changes
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Learning disability
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Irritability
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	5	4	0	0	0	0	0	1
Insomnia
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	3	0	0	0	0	0	1	0
Encopresis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Depression
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0
Product issues
Device malfunction
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Device dislocation
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	5 / 65 (7.69%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	10	0	0	0	2	0	0
Investigations
Activated partial thromboplastin time prolonged
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences all number	1	0	1	0	0	0	0	0	2
Blood albumin decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Blood iron decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	3	1	0	0	0	0	0
Blood potassium decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Bone density decreased
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	3 / 42 (7.14%)	1 / 83 (1.20%)
occurrences all number	1	1	1	0	0	0	1	3	1
Breath sounds abnormal
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	2	0	1	0	0	0	0	0	1
Cardiac murmur
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0
Clostridium test positive
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0
Heart rate increased
subjects affected / exposed	3 / 13 (23.08%)	2 / 24 (8.33%)	4 / 65 (6.15%)	3 / 12 (25.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	0 / 83 (0.00%)
occurrences all number	4	2	4	5	0	0	0	2	0
Electrocardiogram qt prolonged
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	3	0	0	0	0	0	0
Haemoglobin decreased
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	2 / 65 (3.08%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	1	2	1	0	0	0	0	0
Crystal urine present
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	4 / 42 (9.52%)	6 / 83 (7.23%)
occurrences all number	0	0	0	0	0	0	0	4	7
Oxygen consumption decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Occult blood positive
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Mean platelet volume decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Oxygen saturation decreased
subjects affected / exposed	1 / 13 (7.69%)	7 / 24 (29.17%)	18 / 65 (27.69%)	2 / 12 (16.67%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	3 / 83 (3.61%)
occurrences all number	2	9	32	3	0	1	0	2	3
Qrs axis abnormal
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Pseudomonas test positive
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	6 / 65 (9.23%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	1	7	0	0	0	0	0	0
Prothrombin time prolonged
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Platelet count increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Red blood cell count increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Red blood cell sedimentation rate increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Sars-cov-2 test positive
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	1	0	1	1	0	1	0	1	1
Vitamin d decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	0	0	0	0	0	1	1	1	1
White blood cells urine positive
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	0	1	0	0	0	0	1
Weight increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	5 / 42 (11.90%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	0	6	0
Weight decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	3 / 83 (3.61%)
occurrences all number	0	0	3	1	0	1	0	1	3
Von willebrand\'s factor activity decreased
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
White blood cell count increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	4	0	0	0	0	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	6 / 83 (7.23%)
occurrences all number	0	0	1	0	0	0	0	2	6
Arthropod bite
subjects affected / exposed	2 / 13 (15.38%)	1 / 24 (4.17%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	3 / 83 (3.61%)
occurrences all number	2	1	3	0	0	0	0	2	3
Concussion
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	1	0	0	2	1	0	1
Anaesthetic complication neurological
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0
Anaesthetic complication
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	0	0	0	1	1	0	1
Accident
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	2 / 42 (4.76%)	1 / 83 (1.20%)
occurrences all number	1	0	1	0	0	0	1	2	1
Femur fracture
subjects affected / exposed	2 / 13 (15.38%)	3 / 24 (12.50%)	5 / 65 (7.69%)	1 / 12 (8.33%)	2 / 8 (25.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	5 / 42 (11.90%)	8 / 83 (9.64%)
occurrences all number	2	4	7	2	3	0	1	5	8
Fibula fracture
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
Gastrointestinal stoma complication
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Humerus fracture
subjects affected / exposed	3 / 13 (23.08%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	3 / 83 (3.61%)
occurrences all number	3	1	1	0	0	0	0	2	3
Fall
subjects affected / exposed	1 / 13 (7.69%)	3 / 24 (12.50%)	6 / 65 (9.23%)	0 / 12 (0.00%)	0 / 8 (0.00%)	6 / 25 (24.00%)	3 / 20 (15.00%)	9 / 42 (21.43%)	19 / 83 (22.89%)
occurrences all number	1	3	7	0	0	10	3	14	23
Incision site swelling
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Endotracheal intubation complication
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	1	1	0	0	3	0	0
Extraskeletal ossification
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Immunisation reaction
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	1	0	1	0	0	0	1
Post procedural contusion
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Post procedural constipation
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	5 / 65 (7.69%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	8	0	0	0	0	0	0
Post procedural complication
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences all number	1	1	1	0	0	0	0	0	2
Post lumbar puncture syndrome
subjects affected / exposed	2 / 13 (15.38%)	4 / 24 (16.67%)	4 / 65 (6.15%)	0 / 12 (0.00%)	2 / 8 (25.00%)	15 / 25 (60.00%)	13 / 20 (65.00%)	7 / 42 (16.67%)	21 / 83 (25.30%)
occurrences all number	2	4	4	0	2	34	21	18	34
Palate injury
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Lower limb fracture
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	1	0	1	1	0	1	0	0
Post procedural haemorrhage
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	1	1	3	0	0	1	0	1	0
Ligament sprain
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	5 / 25 (20.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	4 / 83 (4.82%)
occurrences all number	0	0	0	1	1	5	1	1	4
Joint dislocation
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	7 / 65 (10.77%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	2 / 20 (10.00%)	3 / 42 (7.14%)	3 / 83 (3.61%)
occurrences all number	2	1	7	0	0	0	2	3	3
Post procedural inflammation
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Procedural hypotension
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	0	1	0	0	0	0	1
Procedural pain
subjects affected / exposed	5 / 13 (38.46%)	5 / 24 (20.83%)	15 / 65 (23.08%)	2 / 12 (16.67%)	2 / 8 (25.00%)	11 / 25 (44.00%)	6 / 20 (30.00%)	19 / 42 (45.24%)	29 / 83 (34.94%)
occurrences all number	6	6	30	2	4	34	12	32	55
Procedural pneumothorax
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Procedural vomiting
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	3 / 83 (3.61%)
occurrences all number	1	0	1	0	0	0	0	1	3
Respiratory tract procedural complication
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	0	0	1	1	0	0	0	1	1
Skin abrasion
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	2 / 65 (3.08%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	1	0	2	1	0	0	0	0	1
Stoma site discharge
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Stoma site erythema
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	2 / 65 (3.08%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	4	2	1	0	0	0	0	0
Stoma site haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	2	0	0	0	0	0	0
Stoma site hypergranulation
subjects affected / exposed	0 / 13 (0.00%)	4 / 24 (16.67%)	5 / 65 (7.69%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	5	5	0	0	0	0	0	0
Suture rupture
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Tibia fracture
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	2 / 42 (4.76%)	4 / 83 (4.82%)
occurrences all number	1	0	3	0	0	0	1	2	4
Tooth fracture
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	3 / 83 (3.61%)
occurrences all number	0	0	0	0	0	0	1	0	3
Wound dehiscence
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	2 / 20 (10.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
Wound secretion
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Congenital, familial and genetic disorders
Developmental hip dysplasia
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	3 / 65 (4.62%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	5 / 83 (6.02%)
occurrences all number	1	1	3	1	1	0	1	3	5
Cryptorchism
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	1	2	0	0	0	0	0	0
High arched palate
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	1	0	0	0	0	0	0
Cardiac disorders
Bradycardia
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	6 / 65 (9.23%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	1	0	7	1	0	0	0	1	0
Tachycardia
subjects affected / exposed	2 / 13 (15.38%)	4 / 24 (16.67%)	5 / 65 (7.69%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	2	4	7	1	0	0	0	1	2
Sinus tachycardia
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	2	1	0	0	0	0	1	0
Right ventricular hypertrophy
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Right atrial enlargement
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Pericardial effusion
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Nervous system disorders
Areflexia
subjects affected / exposed	2 / 13 (15.38%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	2	0	2	0	0	0	1	1	1
Dizziness
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	0	1	0	0	0	2	0	1	2
Disturbance in attention
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Cognitive disorder
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Autonomic nervous system imbalance
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0
Dysarthria
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Migraine
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	1 / 83 (1.20%)
occurrences all number	0	0	0	0	0	2	0	2	1
Lethargy
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	0	0	0	2	0	0	0	1	1
Intracranial pressure increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0
Hyporeflexia
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Horner\'s syndrome
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Headache
subjects affected / exposed	4 / 13 (30.77%)	3 / 24 (12.50%)	8 / 65 (12.31%)	1 / 12 (8.33%)	3 / 8 (37.50%)	17 / 25 (68.00%)	5 / 20 (25.00%)	20 / 42 (47.62%)	24 / 83 (28.92%)
occurrences all number	4	3	9	1	5	47	14	38	53
Motor developmental delay
subjects affected / exposed	3 / 13 (23.08%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	3	0	2	0	0	0	1	0	1
Paraesthesia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	0	0	1	1	0	0	1
Nystagmus
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	4 / 65 (6.15%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	4	1	0	0	0	0	0
Myoclonus
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Muscle contractions involuntary
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 25 (4.00%)	2 / 20 (10.00%)	1 / 42 (2.38%)	4 / 83 (4.82%)
occurrences all number	0	0	0	1	0	1	2	1	4
Tremor
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	3 / 83 (3.61%)
occurrences all number	1	0	1	0	0	2	1	1	3
Blood and lymphatic system disorders
Thrombocytosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	2	1	0	0	0	0	0
Lymphadenopathy
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Leukocytosis
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	1	0	3	0	0	0	0	1	2
Iron deficiency anaemia
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	2	2	0	0	0	0	1	0
Anaemia
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	6 / 65 (9.23%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 25 (0.00%)	2 / 20 (10.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	1	0	8	1	1	0	4	1	1
Ear and labyrinth disorders
Cerumen impaction
subjects affected / exposed	2 / 13 (15.38%)	2 / 24 (8.33%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	2	2	0	1	0	0	0	0	1
Ear pain
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	4 / 83 (4.82%)
occurrences all number	1	0	7	0	0	2	0	0	5
Hyperacusis
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Myringosclerosis
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Motion sickness
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	0	0	0	0	1	0	0	1	1
Eye disorders
Amblyopia
subjects affected / exposed	2 / 13 (15.38%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	2	0	1	0	0	0	0	0	0
Astigmatism
subjects affected / exposed	1 / 13 (7.69%)	2 / 24 (8.33%)	3 / 65 (4.62%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	1	2	3	0	1	1	0	0	1
Chalazion
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	3	1	0	0	0	0	0	0
Eyelid cyst
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Hypermetropia
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Strabismus
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	1	5	0	0	0	0	0	0
Myopia
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	3 / 42 (7.14%)	4 / 83 (4.82%)
occurrences all number	1	1	2	0	0	0	0	3	4
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	3 / 42 (7.14%)	5 / 83 (6.02%)
occurrences all number	0	1	1	1	0	0	0	4	7
Abdominal distension
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	4 / 65 (6.15%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	2 / 83 (2.41%)
occurrences all number	0	0	6	1	0	0	0	4	2
Abdominal pain
subjects affected / exposed	2 / 13 (15.38%)	1 / 24 (4.17%)	4 / 65 (6.15%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	3 / 42 (7.14%)	7 / 83 (8.43%)
occurrences all number	3	2	5	1	0	1	0	3	7
Colitis ulcerative
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0
Constipation
subjects affected / exposed	3 / 13 (23.08%)	7 / 24 (29.17%)	22 / 65 (33.85%)	1 / 12 (8.33%)	3 / 8 (37.50%)	1 / 25 (4.00%)	1 / 20 (5.00%)	9 / 42 (21.43%)	11 / 83 (13.25%)
occurrences all number	4	14	28	3	3	1	1	10	11
Diarrhoea
subjects affected / exposed	4 / 13 (30.77%)	8 / 24 (33.33%)	16 / 65 (24.62%)	2 / 12 (16.67%)	2 / 8 (25.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	6 / 42 (14.29%)	11 / 83 (13.25%)
occurrences all number	5	11	18	3	2	0	1	6	13
Dyspepsia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	0	1	0	1	0	0	1
Gastrointestinal motility disorder
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Gastritis
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences all number	1	1	3	0	0	1	0	0	2
Gastritis haemorrhagic
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	5 / 24 (20.83%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	6	4	0	0	0	0	0	0
Dysphagia
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	5 / 65 (7.69%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	2 / 42 (4.76%)	0 / 83 (0.00%)
occurrences all number	0	2	5	0	0	0	1	3	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 13 (0.00%)	4 / 24 (16.67%)	9 / 65 (13.85%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	4	10	0	0	0	1	0	1
Hiatus hernia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	1	3	0	0	0	0	0
Ileus paralytic
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Oral pain
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Lip dry
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Lip swelling
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Nausea
subjects affected / exposed	2 / 13 (15.38%)	1 / 24 (4.17%)	6 / 65 (9.23%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	2 / 20 (10.00%)	8 / 42 (19.05%)	15 / 83 (18.07%)
occurrences all number	6	1	10	0	0	3	2	11	18
Impaired gastric emptying
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0
Saliva discolouration
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	5	0	0	0	0	0	0	0
Salivary hypersecretion
subjects affected / exposed	1 / 13 (7.69%)	6 / 24 (25.00%)	10 / 65 (15.38%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	1	14	17	0	0	0	0	0	1
Scalloped tongue
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Teething
subjects affected / exposed	0 / 13 (0.00%)	4 / 24 (16.67%)	9 / 65 (13.85%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	4	10	0	0	0	0	0	0
Toothache
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	2	4	0	0	0	0	0	1
Vomiting
subjects affected / exposed	7 / 13 (53.85%)	9 / 24 (37.50%)	23 / 65 (35.38%)	3 / 12 (25.00%)	4 / 8 (50.00%)	4 / 25 (16.00%)	7 / 20 (35.00%)	18 / 42 (42.86%)	35 / 83 (42.17%)
occurrences all number	23	21	53	6	5	15	18	35	64
Tooth impacted
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Hepatobiliary disorders
Hepatic steatosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	2	1	0	0	0	0	0
Skin and subcutaneous tissue disorders
Decubitus ulcer
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	2	3	0	0	0	0	0	1
Acne
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	3 / 25 (12.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences all number	0	0	0	0	0	4	0	0	2
Alopecia
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	1	1	0	0	0	0	0	0
Blister
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	2	0	0	0	0	0	1	0
Dry skin
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Dermatitis diaper
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	2	0	0	0	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 13 (0.00%)	3 / 24 (12.50%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	4 / 83 (4.82%)
occurrences all number	0	4	4	0	0	0	1	0	4
Dermatitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Ecchymosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences all number	0	0	0	0	0	0	1	0	2
Keratosis pilaris
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0
Erythema
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	1	3	0	0	0	0	0	0
Eczema
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	4 / 42 (9.52%)	2 / 83 (2.41%)
occurrences all number	1	1	2	0	0	0	0	6	2
Miliaria
subjects affected / exposed	0 / 13 (0.00%)	3 / 24 (12.50%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	4	2	0	0	0	1	1	0
Petechiae
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Photosensitivity reaction
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Pruritus
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	3 / 83 (3.61%)
occurrences all number	1	0	0	0	0	1	0	0	5
Rash
subjects affected / exposed	1 / 13 (7.69%)	4 / 24 (16.67%)	7 / 65 (10.77%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	2 / 20 (10.00%)	6 / 42 (14.29%)	8 / 83 (9.64%)
occurrences all number	1	7	8	0	0	0	2	7	10
Scab
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0
Skin mass
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0	0
Urticaria
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	3 / 42 (7.14%)	6 / 83 (7.23%)
occurrences all number	0	2	3	0	0	0	0	3	9
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences all number	0	0	1	1	0	0	0	0	2
Pollakiuria
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	3 / 83 (3.61%)
occurrences all number	0	1	0	0	0	0	1	2	4
Proteinuria
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	7 / 65 (10.77%)	1 / 12 (8.33%)	0 / 8 (0.00%)	2 / 25 (8.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	8 / 83 (9.64%)
occurrences all number	0	2	11	1	0	2	0	4	14
Urinary retention
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	1	1	3	0	0	0	0	0	1
Kidney enlargement
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Haematuria
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences all number	1	1	0	0	0	0	0	0	4
Dysuria
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	0	1	0	1	0	0	1	0
Endocrine disorders
Precocious puberty
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	2	5	0	0	0	1	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 13 (15.38%)	3 / 24 (12.50%)	4 / 65 (6.15%)	2 / 12 (16.67%)	0 / 8 (0.00%)	3 / 25 (12.00%)	3 / 20 (15.00%)	5 / 42 (11.90%)	6 / 83 (7.23%)
occurrences all number	2	3	5	2	0	3	6	5	7
Deformity thorax
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Bone pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	0	1	0	0	0	1	2	0
Back pain
subjects affected / exposed	1 / 13 (7.69%)	2 / 24 (8.33%)	7 / 65 (10.77%)	2 / 12 (16.67%)	1 / 8 (12.50%)	11 / 25 (44.00%)	3 / 20 (15.00%)	11 / 42 (26.19%)	15 / 83 (18.07%)
occurrences all number	1	4	7	2	1	15	3	14	16
Foot deformity
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	3 / 83 (3.61%)
occurrences all number	0	0	1	1	0	1	0	0	4
Knee deformity
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Joint range of motion decreased
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	0	2	3	0	0	0	0	1	2
Joint laxity
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
Joint contracture
subjects affected / exposed	4 / 13 (30.77%)	6 / 24 (25.00%)	16 / 65 (24.62%)	2 / 12 (16.67%)	1 / 8 (12.50%)	3 / 25 (12.00%)	8 / 20 (40.00%)	11 / 42 (26.19%)	21 / 83 (25.30%)
occurrences all number	7	11	26	2	1	3	13	16	38
Hip deformity
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	9 / 65 (13.85%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 25 (0.00%)	2 / 20 (10.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	2	0	17	0	4	0	2	1	3
Kyphoscoliosis
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	5 / 65 (7.69%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	3 / 83 (3.61%)
occurrences all number	0	2	7	0	0	0	0	1	6
Kyphosis
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	10 / 65 (15.38%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 25 (4.00%)	1 / 20 (5.00%)	2 / 42 (4.76%)	3 / 83 (3.61%)
occurrences all number	1	0	15	0	1	1	1	2	3
Muscle atrophy
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Muscle contracture
subjects affected / exposed	5 / 13 (38.46%)	6 / 24 (25.00%)	18 / 65 (27.69%)	2 / 12 (16.67%)	1 / 8 (12.50%)	1 / 25 (4.00%)	6 / 20 (30.00%)	17 / 42 (40.48%)	37 / 83 (44.58%)
occurrences all number	6	8	44	2	1	2	19	38	67
Muscle spasms
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 65 (4.62%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	0	3	1	0	0	1	1	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	1	1	2	0
Limb asymmetry
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Musculoskeletal stiffness
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	1	0	1	0	0	0	0	1	1
Pain in extremity
subjects affected / exposed	1 / 13 (7.69%)	4 / 24 (16.67%)	7 / 65 (10.77%)	1 / 12 (8.33%)	1 / 8 (12.50%)	6 / 25 (24.00%)	1 / 20 (5.00%)	4 / 42 (9.52%)	6 / 83 (7.23%)
occurrences all number	1	5	10	2	1	11	1	6	6
Pathological fracture
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
Scoliosis
subjects affected / exposed	6 / 13 (46.15%)	10 / 24 (41.67%)	38 / 65 (58.46%)	3 / 12 (25.00%)	5 / 8 (62.50%)	2 / 25 (8.00%)	6 / 20 (30.00%)	22 / 42 (52.38%)	33 / 83 (39.76%)
occurrences all number	6	10	60	3	8	2	7	32	48
Spinal deformity
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Neck pain
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	1	0	0	0	0	0	0	1	1
Neuromuscular scoliosis
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	1	2	0	0	0	2	0	1
Osteopenia
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	9 / 65 (13.85%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	2 / 20 (10.00%)	1 / 42 (2.38%)	3 / 83 (3.61%)
occurrences all number	0	1	10	0	0	0	2	1	3
Osteoporosis
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	7 / 65 (10.77%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 25 (0.00%)	2 / 20 (10.00%)	2 / 42 (4.76%)	0 / 83 (0.00%)
occurrences all number	1	1	7	0	2	0	2	2	0
Tendinous contracture
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	2	1	2	0	0	0	0	1	2
Infections and infestations
Abdominal abscess
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Bronchiolitis
subjects affected / exposed	2 / 13 (15.38%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	2	0	2	0	0	0	0	0	0
Adenovirus infection
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	0	2	0	0	0	0	0	1	2
Bacterial disease carrier
subjects affected / exposed	0 / 13 (0.00%)	4 / 24 (16.67%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	7	4	0	0	0	0	0	2
Bacterial infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0
Acute sinusitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	0	0	0	0	1	0	1
Coronavirus infection
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	1	3	0	0	0	0	0	0
Covid-19
subjects affected / exposed	4 / 13 (30.77%)	1 / 24 (4.17%)	16 / 65 (24.62%)	5 / 12 (41.67%)	2 / 8 (25.00%)	5 / 25 (20.00%)	4 / 20 (20.00%)	8 / 42 (19.05%)	16 / 83 (19.28%)
occurrences all number	4	1	18	6	3	6	4	8	19
Coxsackie viral infection
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0
Conjunctivitis
subjects affected / exposed	2 / 13 (15.38%)	3 / 24 (12.50%)	8 / 65 (12.31%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	4 / 83 (4.82%)
occurrences all number	2	4	10	0	0	0	0	1	4
Bronchitis
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	10 / 65 (15.38%)	2 / 12 (16.67%)	1 / 8 (12.50%)	0 / 25 (0.00%)	2 / 20 (10.00%)	7 / 42 (16.67%)	5 / 83 (6.02%)
occurrences all number	1	1	15	2	1	0	4	9	5
Cellulitis
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	2	0	0	0	0	0	0
Clostridium difficile infection
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	2	0	0	0	0	0
Croup infectious
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Cystitis
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	3 / 83 (3.61%)
occurrences all number	0	1	0	1	0	0	0	1	3
Ear infection
subjects affected / exposed	2 / 13 (15.38%)	3 / 24 (12.50%)	21 / 65 (32.31%)	2 / 12 (16.67%)	1 / 8 (12.50%)	1 / 25 (4.00%)	3 / 20 (15.00%)	5 / 42 (11.90%)	14 / 83 (16.87%)
occurrences all number	2	6	31	2	1	1	3	6	19
Ear infection fungal
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	1	1	0	0	0	0	0
Enterovirus infection
subjects affected / exposed	0 / 13 (0.00%)	4 / 24 (16.67%)	4 / 65 (6.15%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	0	6	4	1	0	0	0	1	2
Gastroenteritis viral
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	4 / 65 (6.15%)	1 / 12 (8.33%)	1 / 8 (12.50%)	5 / 25 (20.00%)	7 / 20 (35.00%)	5 / 42 (11.90%)	3 / 83 (3.61%)
occurrences all number	0	1	4	1	1	5	7	5	7
Fungal skin infection
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	1	2	0	0	0	3	1	0
Gastritis viral
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	2 / 20 (10.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	2	1	0
Gastroenteritis
subjects affected / exposed	1 / 13 (7.69%)	2 / 24 (8.33%)	9 / 65 (13.85%)	2 / 12 (16.67%)	1 / 8 (12.50%)	0 / 25 (0.00%)	3 / 20 (15.00%)	4 / 42 (9.52%)	11 / 83 (13.25%)
occurrences all number	1	3	10	2	3	0	3	10	15
Eye infection
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0
Gastrointestinal viral infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	0	0	2	1	0	0	0	1	1
Hand-foot-and-mouth disease
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	3 / 83 (3.61%)
occurrences all number	1	0	0	0	0	0	0	1	3
Hordeolum
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	4 / 65 (6.15%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	0	2	4	1	0	0	0	1	3
Impetigo
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	0	3	0	0	0	0	1	1	2
Influenza
subjects affected / exposed	2 / 13 (15.38%)	3 / 24 (12.50%)	13 / 65 (20.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	3 / 25 (12.00%)	4 / 20 (20.00%)	6 / 42 (14.29%)	16 / 83 (19.28%)
occurrences all number	4	3	14	0	1	4	4	11	20
Klebsiella infection
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0
Lower respiratory tract infection
subjects affected / exposed	1 / 13 (7.69%)	3 / 24 (12.50%)	4 / 65 (6.15%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	3 / 83 (3.61%)
occurrences all number	1	3	7	0	1	0	0	0	4
Lower respiratory tract infection viral
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Metapneumovirus infection
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Otitis externa
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	4 / 65 (6.15%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	3 / 83 (3.61%)
occurrences all number	2	0	8	1	0	0	0	0	3
Oral fungal infection
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	3	1	0	0	0	0	0	0
Otitis media
subjects affected / exposed	4 / 13 (30.77%)	4 / 24 (16.67%)	14 / 65 (21.54%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 25 (0.00%)	4 / 20 (20.00%)	5 / 42 (11.90%)	6 / 83 (7.23%)
occurrences all number	7	7	23	1	1	0	4	10	8
Otitis media acute
subjects affected / exposed	2 / 13 (15.38%)	2 / 24 (8.33%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	2 / 83 (2.41%)
occurrences all number	2	2	3	0	0	0	0	2	2
Moraxella infection
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	2	0	0	0	0	0	0
Mycoplasma infection
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	4 / 13 (30.77%)	5 / 24 (20.83%)	26 / 65 (40.00%)	4 / 12 (33.33%)	1 / 8 (12.50%)	8 / 25 (32.00%)	4 / 20 (20.00%)	13 / 42 (30.95%)	27 / 83 (32.53%)
occurrences all number	14	20	74	5	1	10	7	37	72
Oral candidiasis
subjects affected / exposed	1 / 13 (7.69%)	3 / 24 (12.50%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 83 (0.00%)
occurrences all number	1	3	0	0	0	0	0	1	0
Pneumonia
subjects affected / exposed	4 / 13 (30.77%)	6 / 24 (25.00%)	18 / 65 (27.69%)	4 / 12 (33.33%)	1 / 8 (12.50%)	0 / 25 (0.00%)	1 / 20 (5.00%)	6 / 42 (14.29%)	11 / 83 (13.25%)
occurrences all number	9	8	24	5	3	0	1	6	21
Pharyngitis streptococcal
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	1 / 8 (12.50%)	3 / 25 (12.00%)	3 / 20 (15.00%)	4 / 42 (9.52%)	8 / 83 (9.64%)
occurrences all number	1	0	3	0	1	3	4	6	16
Pseudomonas infection
subjects affected / exposed	0 / 13 (0.00%)	6 / 24 (25.00%)	11 / 65 (16.92%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	10	17	0	0	0	0	0	0
Parainfluenzae virus infection
subjects affected / exposed	2 / 13 (15.38%)	0 / 24 (0.00%)	5 / 65 (7.69%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	2	0	5	0	0	0	0	0	0
Pharyngitis
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	4 / 42 (9.52%)	3 / 83 (3.61%)
occurrences all number	0	2	4	0	0	0	1	5	3
Pneumonia bacterial
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	1	1	0	0	0	0	1
Postoperative wound infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	0	0	1	1	0	0	0	2	1
Respiratory syncytial virus infection
subjects affected / exposed	2 / 13 (15.38%)	2 / 24 (8.33%)	8 / 65 (12.31%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	1 / 83 (1.20%)
occurrences all number	3	2	10	0	1	0	0	2	1
Pneumonia aspiration
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	7 / 65 (10.77%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	8	0	0	0	0	0	0
Respiratory tract infection
subjects affected / exposed	4 / 13 (30.77%)	2 / 24 (8.33%)	22 / 65 (33.85%)	1 / 12 (8.33%)	2 / 8 (25.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	3 / 42 (7.14%)	8 / 83 (9.64%)
occurrences all number	16	4	44	1	3	0	0	9	10
Respiratory tract infection viral
subjects affected / exposed	2 / 13 (15.38%)	1 / 24 (4.17%)	6 / 65 (9.23%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 25 (0.00%)	2 / 20 (10.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	3	1	7	0	4	0	3	1	2
Rhinitis
subjects affected / exposed	0 / 13 (0.00%)	6 / 24 (25.00%)	5 / 65 (7.69%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	3 / 42 (7.14%)	8 / 83 (9.64%)
occurrences all number	0	7	17	1	0	0	0	4	16
Rhinovirus infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	12 / 65 (18.46%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	3 / 42 (7.14%)	3 / 83 (3.61%)
occurrences all number	0	0	20	2	0	0	1	3	4
Serratia infection
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0
Sinusitis
subjects affected / exposed	1 / 13 (7.69%)	2 / 24 (8.33%)	6 / 65 (9.23%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 25 (0.00%)	2 / 20 (10.00%)	3 / 42 (7.14%)	6 / 83 (7.23%)
occurrences all number	1	2	6	2	0	0	2	3	13
Staphylococcal infection
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	7 / 65 (10.77%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	1	11	3	0	0	0	0	0
Stenotrophomonas infection
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	1	0	0	0	0	0	0
Respiratory tract infection bacterial
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Stoma site infection
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	4 / 65 (6.15%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	1	2	5	0	0	0	0	0	0
Suspected covid-19
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Tonsillitis
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	3 / 42 (7.14%)	6 / 83 (7.23%)
occurrences all number	1	1	2	0	0	1	0	3	6
Tooth abscess
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Stoma site cellulitis
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	6	2	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	11 / 13 (84.62%)	14 / 24 (58.33%)	34 / 65 (52.31%)	3 / 12 (25.00%)	6 / 8 (75.00%)	5 / 25 (20.00%)	8 / 20 (40.00%)	21 / 42 (50.00%)	33 / 83 (39.76%)
occurrences all number	16	35	109	6	18	10	14	56	63
Upper respiratory tract infection bacterial
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	3 / 13 (23.08%)	3 / 24 (12.50%)	10 / 65 (15.38%)	1 / 12 (8.33%)	1 / 8 (12.50%)	1 / 25 (4.00%)	2 / 20 (10.00%)	4 / 42 (9.52%)	7 / 83 (8.43%)
occurrences all number	5	7	20	2	1	3	3	8	12
Tracheitis
subjects affected / exposed	0 / 13 (0.00%)	4 / 24 (16.67%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	5	8	0	0	0	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	2 / 13 (15.38%)	1 / 24 (4.17%)	5 / 65 (7.69%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	3 / 20 (15.00%)	4 / 42 (9.52%)	4 / 83 (4.82%)
occurrences all number	3	1	14	0	0	2	4	5	5
Viral infection
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	3 / 65 (4.62%)	0 / 12 (0.00%)	1 / 8 (12.50%)	4 / 25 (16.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	10 / 83 (12.05%)
occurrences all number	2	1	3	0	2	5	0	7	11
Metabolism and nutrition disorders
Feeding intolerance
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	1	1	0	0	0	0	0	0	1
Electrolyte imbalance
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	1	1	0	0	0	0	1
Dehydration
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	6 / 65 (9.23%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	4 / 42 (9.52%)	2 / 83 (2.41%)
occurrences all number	0	3	7	2	0	1	1	4	2
Hypocalcaemia
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	0 / 65 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	3	0	0	0	0	0	0	1
Hyponatraemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 83 (1.20%)
occurrences all number	0	0	1	1	0	0	0	0	1
Hypokalaemia
subjects affected / exposed	1 / 13 (7.69%)	3 / 24 (12.50%)	10 / 65 (15.38%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	2 / 83 (2.41%)
occurrences all number	1	5	11	0	0	0	0	1	3
Hypoglycaemia
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	1	0	4	0	0	0	0	2	1
Hypochloraemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Malnutrition
subjects affected / exposed	1 / 13 (7.69%)	0 / 24 (0.00%)	6 / 65 (9.23%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	4 / 83 (4.82%)
occurrences all number	1	0	6	0	0	0	0	0	4
Iron deficiency
subjects affected / exposed	0 / 13 (0.00%)	2 / 24 (8.33%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	2	2	0	0	0	0	0	0
Hypovolaemia
subjects affected / exposed	0 / 13 (0.00%)	1 / 24 (4.17%)	1 / 65 (1.54%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	1	1	1	0	0	0	0	0
Metabolic acidosis
subjects affected / exposed	2 / 13 (15.38%)	1 / 24 (4.17%)	2 / 65 (3.08%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	2 / 83 (2.41%)
occurrences all number	2	1	2	0	0	0	0	2	2
Obesity
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 65 (1.54%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 25 (8.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	4 / 83 (4.82%)
occurrences all number	0	0	1	0	0	2	0	2	4
Vitamin d deficiency
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 65 (3.08%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 83 (1.20%)
occurrences all number	0	0	2	0	1	0	0	1	1
Weight gain poor
subjects affected / exposed	1 / 13 (7.69%)	1 / 24 (4.17%)	3 / 65 (4.62%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 83 (2.41%)
occurrences all number	1	2	3	0	0	0	0	0	2
Metabolic alkalosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 65 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 83 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

01 Nov 2015

Allowed inclusion of participants who completed Study CS12 into Study CS11, and to provide clarifications and corrections to the original CS11 study protocol dated 12 May 2015.

30 Jan 2017

Transitioned the dosing regimen for the open-label maintenance dosing period for all index studies (ISIS 396443-CS3B [Groups 1A and 1B], ISIS 396443-CS4 [Groups 2A and 2B], ISIS 396443-CS12 [Group 3], and ISIS 396443-CS3A [Group 4]) to the MMDR schedule, during which maintenance doses of nusinersen were administered every 4 months.

29 Oct 2017

Allowed enrollment of participants from the newly added index study 232SM202 into this extension study. As a result of this change, the approximate number of participants had increased from 239 to 292 participants, the approximate number of study sites from 37 up to 45 sites, and the approximate number of countries from 14 up to 15 worldwide. Participants entering the extension study from the index study 232SM202 were enrolled into a new cohort, Group 5. Participants entered directly into the open-label period at MMDR Day 1.

18 Nov 2019

Changed the interval of clinical assessment visits after the Modified Maintenance Dosing Regimen (MMDR) Day 720 Visit from every 8 months to every 12 months.

23 Mar 2020

Changed the standard neurological examination to a focused neurological examination.

20 Oct 2021

Limited the number of participants who were receiving nusinersen concomitantly with other SMA therapies to 20% (n = 58) of the total population.

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 Extension Study for Patients With Spinal Muscular Atrophy Who Previously Participated in Investigational Studies of ISIS 396443

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Primary: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Primary: Number of Participants With Clinically Significant Vital Sign Parameters

Primary: Number of Participants With Clinically Significant Vital Sign Parameters

Primary: Number of Participants With Clinically Significant Change From Baseline in Weight

Primary: Number of Participants With Clinically Significant Change From Baseline in Weight

Primary: Number of Participants With Clinically Significant Neurological Examination Abnormalities

Primary: Number of Participants With Clinically Significant Neurological Examination Abnormalities

Primary: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities

Primary: Number of Participants With Clinically Significant Laboratory Assessment Abnormalities

Primary: Number of Participants With Shift From Baseline in Coagulation Parameters

Primary: Number of Participants With Shift From Baseline in Coagulation Parameters

Primary: Number of Participants With Clinically Significant Shifts in 12 Lead Electrocardiogram (ECG) Results

Primary: Number of Participants With Clinically Significant Shifts in 12 Lead Electrocardiogram (ECG) Results

Primary: Number of Participants Taking any Concomitant Medication

Primary: Number of Participants Taking any Concomitant Medication

Secondary: Percentage of Participants With <2 Years of Age Who Attained Motor Milestones as Assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE)

Secondary: Percentage of Participants With <2 Years of Age Who Attained Motor Milestones as Assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE)

Secondary: Mean Number of new Motor Milestones Achieved as Assessed by World Health Organization (WHO) Criteria

Secondary: Mean Number of new Motor Milestones Achieved as Assessed by World Health Organization (WHO) Criteria

Secondary: Number of Participants who Died or met Permanent Ventilation

Secondary: Number of Participants who Died or met Permanent Ventilation

Secondary: Number of Participants not Requiring Permanent Ventilation

Secondary: Number of Participants not Requiring Permanent Ventilation

Secondary: Change From Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale

Secondary: Change From Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale

Secondary: Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Total Score

Secondary: Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Total Score

Secondary: Change from Baseline in Revised Upper Limb Module (RULM) Total Score

Secondary: Change from Baseline in Revised Upper Limb Module (RULM) Total Score

Secondary: Change From Baseline in Total Distance Walked Over Time as Assessed by 6-Minute Walk Test (6MWT)

Secondary: Change From Baseline in Total Distance Walked Over Time as Assessed by 6-Minute Walk Test (6MWT)

Secondary: Number of Participants who Experienced Contracture Assessment

Secondary: Number of Participants who Experienced Contracture Assessment

Secondary: Change From Baseline in Compound Muscular Action Potential (CMAP)

Secondary: Change From Baseline in Compound Muscular Action Potential (CMAP)

Secondary: Change From Baseline in Body Length

Secondary: Change From Baseline in Body Length

Secondary: Change From Baseline in Weight

Secondary: Change From Baseline in Weight

Secondary: Change From Baseline in Weight for Age Percentile

Secondary: Change From Baseline in Weight for Age Percentile

Secondary: Percentage of CMAP Responders

Secondary: Percentage of CMAP Responders

Secondary: Number of Participants who Achieved Motor Milestones

Secondary: Number of Participants who Achieved Motor Milestones

Secondary: Number of Participants who Achieved Standing Alone and Walking With Assistance

Secondary: Number of Participants who Achieved Standing Alone and Walking With Assistance

Secondary: Total Number of Hospitalizations due to Serious Respiratory Events

Secondary: Total Number of Hospitalizations due to Serious Respiratory Events

Secondary: Total Number of Hospitalizations Due to Serious Adverse Events

Secondary: Total Number of Hospitalizations Due to Serious Adverse Events

Secondary: Percent of Time in Hospitalization

Secondary: Percent of Time in Hospitalization

Secondary: Change From Baseline in Cobb-Angle on X-Ray of the Thoracolumbar Spine

Secondary: Change From Baseline in Cobb-Angle on X-Ray of the Thoracolumbar Spine

Secondary: Pediatric Quality of Life Inventory (PedsQL) Questionnaires Total Score by Domain

Secondary: Pediatric Quality of Life Inventory (PedsQL) Questionnaires Total Score by Domain

Secondary: Change From Baseline in Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) Questionnaire Total Score

Secondary: Change From Baseline in Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) Questionnaire Total Score

Secondary: Number of Participants With Disease-related Hospitalizations and AEs

Secondary: Number of Participants With Disease-related Hospitalizations and AEs

Secondary: Survival Rate

Secondary: Survival Rate

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Clinical Trial Results:
An Open-Label Extension Study for Patients With Spinal Muscular Atrophy Who Previously Participated in Investigational Studies of ISIS 396443