Download PDF

Clinical Trial Results:
An Early-Phase, Multicenter, Open-Label Study of the Safety and Pharmacokinetics of Atezolizumab (MPDL3280A) In Pediatric and Young Adult Patients With Previously Treated Solid Tumors

Summary
EudraCT number	2014-004697-41
Trial protocol	DK DE IE ES FR AT NL IT
Global end of trial date	06 Jun 2019

Results information
Results version number	v1
This version publication date	27 Nov 2019
First version publication date	27 Nov 2019
Other versions	v2 , v3

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

GO29664

ISRCTN number

US NCT number

NCT02541604

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland,

Public contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-001638-PIP01-14

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

06 Jun 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

06 Jun 2019

Global end of trial reached?

Yes

Global end of trial date

06 Jun 2019

Was the trial ended prematurely?

Yes

Main objective of the trial

This study evaluated the safety, tolerability, PK, pharmacodynamics, immunogenicity, and preliminary efficacy of atezolizumab administered by IV infusion every 3 weeks to pediatric and young adult patients with solid tumors for which prior treatment has proven to be ineffective (i.e., relapsed or refractory) or intolerable and for whom there is no effective standard treatment available.

Protection of trial subjects

All study subjects were required to read and sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

05 Nov 2015

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

6 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Switzerland: 2

Country: Number of subjects enrolled

Germany: 1

Country: Number of subjects enrolled

Denmark: 4

Country: Number of subjects enrolled

Spain: 9

Country: Number of subjects enrolled

France: 17

Country: Number of subjects enrolled

United Kingdom: 9

Country: Number of subjects enrolled

Israel: 2

Country: Number of subjects enrolled

Italy: 16

Country: Number of subjects enrolled

Netherlands: 8

Country: Number of subjects enrolled

United States: 19

Worldwide total number of subjects

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)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

Subjects in this study included pediatric and young adult patients with solid tumors with known or expected PD-L1 pathway involvement for which prior treatment has proven to be ineffective (i.e., relapsed or refractory) or intolerable, and for whom no curative standard-of-care treatment options exist.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

COHORT 1 (EWING SARCOMA)

Arm description

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle

COHORT 2 (HODGKIN LYMPHOMA)

Arm description

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle

COHORT 3 (NEUROBLASTOMA)

Arm description

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle

COHORT 4 (NON HODGKIN LYMPHOMA)

Arm description

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle

COHORT 5 (NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA)

Arm description

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle

COHORT 6 (OSTEOSARCOMA)

Arm description

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle

COHORT 7 (RHABDOMYOSARCOMA)

Arm description

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle

COHORT 8 (WILMS TUMOR)

Arm description

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle

COHORT 9 (OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION)

Arm description

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle

COHORT 10 (OTHER TUMOR TYPES WITHOUT PD-L1 EXPRESSION)

Arm description

OTHER TUMOR TYPES WITHOUT DOCUMENTED PD-L1 EXPRESSION

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle

COHORT 11 (RHABDOID TUMOR)

Arm description

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle

COHORT 12 (ATYPICAL TERATOID RHABDOID TUMOR)

Arm description

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle

Number of subjects in period 1	COHORT 1 (EWING SARCOMA)	COHORT 2 (HODGKIN LYMPHOMA)	COHORT 3 (NEUROBLASTOMA)	COHORT 4 (NON HODGKIN LYMPHOMA)	COHORT 5 (NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA)	COHORT 6 (OSTEOSARCOMA)	COHORT 7 (RHABDOMYOSARCOMA)	COHORT 8 (WILMS TUMOR)	COHORT 9 (OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION)	COHORT 10 (OTHER TUMOR TYPES WITHOUT PD-L1 EXPRESSION)	COHORT 11 (RHABDOID TUMOR)	COHORT 12 (ATYPICAL TERATOID RHABDOID TUMOR)
Started	11	9	11	3	10	10	10	10	4	4	2	3
Completed	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	11	9	11	3	10	10	10	10	4	4	2	3
Consent withdrawn by subject	2	-	1	-	1	1	-	-	1	-	-	-
Death	6	5	7	2	9	8	9	9	3	4	2	3
Study Terminated by Sponsor	1	4	2	1	-	-	-	-	-	-	-	-
Lost to follow-up	2	-	1	-	-	1	1	-	-	-	-	-
Medical condition may jeopardize safety	-	-	-	-	-	-	-	1	-	-	-	-

Baseline characteristics

Top of page

Reporting group title

COHORT 1 (EWING SARCOMA)

Reporting group description

Reporting group title

COHORT 2 (HODGKIN LYMPHOMA)

Reporting group description

Reporting group title

COHORT 3 (NEUROBLASTOMA)

Reporting group description

Reporting group title

COHORT 4 (NON HODGKIN LYMPHOMA)

Reporting group description

Reporting group title

COHORT 5 (NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA)

Reporting group description

Reporting group title

COHORT 6 (OSTEOSARCOMA)

Reporting group description

Reporting group title

COHORT 7 (RHABDOMYOSARCOMA)

Reporting group description

Reporting group title

COHORT 8 (WILMS TUMOR)

Reporting group description

Reporting group title

COHORT 9 (OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION)

Reporting group description

Reporting group title

COHORT 10 (OTHER TUMOR TYPES WITHOUT PD-L1 EXPRESSION)

Reporting group description

OTHER TUMOR TYPES WITHOUT DOCUMENTED PD-L1 EXPRESSION

Reporting group title

COHORT 11 (RHABDOID TUMOR)

Reporting group description

Reporting group title

COHORT 12 (ATYPICAL TERATOID RHABDOID TUMOR)

Reporting group description

Reporting group values	COHORT 1 (EWING SARCOMA)	COHORT 2 (HODGKIN LYMPHOMA)	COHORT 3 (NEUROBLASTOMA)	COHORT 4 (NON HODGKIN LYMPHOMA)	COHORT 5 (NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA)	COHORT 6 (OSTEOSARCOMA)	COHORT 7 (RHABDOMYOSARCOMA)	COHORT 8 (WILMS TUMOR)	COHORT 9 (OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION)	COHORT 10 (OTHER TUMOR TYPES WITHOUT PD-L1 EXPRESSION)	COHORT 11 (RHABDOID TUMOR)	COHORT 12 (ATYPICAL TERATOID RHABDOID TUMOR)	Total
Number of subjects	11	9	11	3	10	10	10	10	4	4	2	3	87
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	1	0	1
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0	1	0	1
Children (2-11 years)	3	2	6	0	2	0	5	5	0	3	0	3	29
Adolescents (12-17 years)	7	7	2	1	5	5	2	4	4	1	0	0	38
Adults (18-64 years)	1	0	3	2	3	5	3	1	0	0	0	0	18
From 65-84 years	0	0	0	0	0	0	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0	0	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	13.6 ± 3.3	14.2 ± 3.0	12.8 ± 9.4	19.0 ± 6.6	14.5 ± 6.5	17.1 ± 4.1	13.0 ± 8.5	12.6 ± 6.8	14.8 ± 1.0	11.3 ± 0.5	0.5 ± 0.7	7.3 ± 4.6	-
Gender categorical
Units: Subjects
Female	5	6	4	0	5	4	4	6	0	4	1	1	40
Male	6	3	7	3	5	6	6	4	4	0	1	2	47
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	2	1	2	1	1	2	3	1	2	0	0	1	16
Not Hispanic or Latino	7	5	7	2	5	6	6	6	2	3	2	0	51
Unknown or Not Reported	2	3	2	0	4	2	1	3	0	1	0	2	20
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	1	0	0	1	0	0	1	3
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	1	1	0	1	0	1	1	1	0	0	6
White	8	5	5	2	6	6	8	5	1	2	2	0	50
More than one race	1	0	1	0	0	0	0	0	0	0	0	0	2
Unknown or Not Reported	2	4	4	0	4	2	2	4	1	1	0	2	26

Subject analysis set title

Atezolizumab

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received intravenous (IV) infusion of atezolizumab (maximum 1200 milligrams [mg]) on Day 1 of each 21-day cycle.

Subject analysis set title

<2 Age (Years)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects <2 Age (Years)

Subject analysis set title

2 to <12 Age (Years)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects 2 to <12 Age (Years)

Subject analysis set title

12 to <18 Age (Years)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects 12 to <18 Age (Years)

Subject analysis set title

>=18 Age (Years)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects >=18 Age (Years)

Subject analysis sets values	Atezolizumab	<2 Age (Years)	2 to <12 Age (Years)	12 to <18 Age (Years)	>=18 Age (Years)
Number of subjects	87	2	29	38	18
Age categorical
Units: Subjects
In utero	0
Preterm newborn infants (gestational age < 37 wks)	0
Newborns (0-27 days)	1
Infants and toddlers (28 days-23 months)	1
Children (2-11 years)	29
Adolescents (12-17 years)	38
Adults (18-64 years)	18
From 65-84 years	0
85 years and over	0
Age continuous
Units: years
arithmetic mean (standard deviation)	13.5 ± 6.4	±	±	±	±
Gender categorical
Units: Subjects
Female	40
Male	47
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	16
Not Hispanic or Latino	51
Unknown or Not Reported	20
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0
Asian	3
Native Hawaiian or Other Pacific Islander	0
Black or African American	6
White	50
More than one race	2
Unknown or Not Reported	26

End points

Top of page

Reporting group title

COHORT 1 (EWING SARCOMA)

Reporting group description

Reporting group title

COHORT 2 (HODGKIN LYMPHOMA)

Reporting group description

Reporting group title

COHORT 3 (NEUROBLASTOMA)

Reporting group description

Reporting group title

COHORT 4 (NON HODGKIN LYMPHOMA)

Reporting group description

Reporting group title

COHORT 5 (NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA)

Reporting group description

Reporting group title

COHORT 6 (OSTEOSARCOMA)

Reporting group description

Reporting group title

COHORT 7 (RHABDOMYOSARCOMA)

Reporting group description

Reporting group title

COHORT 8 (WILMS TUMOR)

Reporting group description

Reporting group title

COHORT 9 (OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION)

Reporting group description

Reporting group title

COHORT 10 (OTHER TUMOR TYPES WITHOUT PD-L1 EXPRESSION)

Reporting group description

OTHER TUMOR TYPES WITHOUT DOCUMENTED PD-L1 EXPRESSION

Reporting group title

COHORT 11 (RHABDOID TUMOR)

Reporting group description

Reporting group title

COHORT 12 (ATYPICAL TERATOID RHABDOID TUMOR)

Reporting group description

Subject analysis set title

Atezolizumab

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received intravenous (IV) infusion of atezolizumab (maximum 1200 milligrams [mg]) on Day 1 of each 21-day cycle.

Subject analysis set title

<2 Age (Years)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects <2 Age (Years)

Subject analysis set title

2 to <12 Age (Years)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects 2 to <12 Age (Years)

Subject analysis set title

12 to <18 Age (Years)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects 12 to <18 Age (Years)

Subject analysis set title

>=18 Age (Years)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects >=18 Age (Years)

Primary: Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Participants With Solid Tumors

Top of page

End point title

Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Participants With Solid Tumors ^[1] ^[2]

End point description

Note: In Cohort 5, the response was observed in a rhabdoid tumor. Participant was erroneously enrolled in the Non-rhabdomyosarcoma soft tissue sarcoma cohort.

End point type

Primary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

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: No statistical analysis for this end point.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this end point.

End point values	COHORT 1 (EWING SARCOMA)	COHORT 5 (NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA)	COHORT 6 (OSTEOSARCOMA)	COHORT 7 (RHABDOMYOSARCOMA)	COHORT 8 (WILMS TUMOR)	COHORT 9 (OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION)	COHORT 10 (OTHER TUMOR TYPES WITHOUT PD-L1 EXPRESSION)	COHORT 11 (RHABDOID TUMOR)
Number of subjects analysed	11	10	10	10	10	4	4	2
Units: Percentage
number (not applicable)	0	10	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Top of page

End point title

Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma ^[3] ^[4]

End point description

End point type

Primary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

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: No statistical analysis for this end point.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this end point.

End point values	COHORT 2 (HODGKIN LYMPHOMA)	COHORT 4 (NON HODGKIN LYMPHOMA)
Number of subjects analysed	9	3
Units: Percentage
number (not applicable)	22.2	33.3

No statistical analyses for this end point

Primary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Modified International Neuroblastoma Response Criteria (mINRC) in Participants With Neuroblastoma

Top of page

End point title

Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Modified International Neuroblastoma Response Criteria (mINRC) in Participants With Neuroblastoma ^[5] ^[6]

End point description

End point type

Primary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

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: No statistical analysis for this end point.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this end point.

End point values	COHORT 3 (NEUROBLASTOMA)
Number of subjects analysed	11
Units: Percentage	0

No statistical analyses for this end point

Primary: Percentage of Participants With Clinical Benefit as Determined by the Investigator According to RECIST v1.1 Criteria in Participants With Osteosarcoma

Top of page

End point title

Percentage of Participants With Clinical Benefit as Determined by the Investigator According to RECIST v1.1 Criteria in Participants With Osteosarcoma ^[7] ^[8]

End point description

End point type

Primary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

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: No statistical analysis for this end point.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this end point.

End point values	COHORT 6 (OSTEOSARCOMA)
Number of subjects analysed	10
Units: Percentage	0

No statistical analyses for this end point

Primary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Response Assessment in Neuro-Oncology (RANO) Criteria in Participants With Atypical Teratoid Rhabdoid Tumor (ATRT)

Top of page

End point title

Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Response Assessment in Neuro-Oncology (RANO) Criteria in Participants With Atypical Teratoid Rhabdoid Tumor (ATRT) ^[9] ^[10]

End point description

End point type

Primary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[9] - 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: No statistical analysis for this end point.
[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: No statistical analysis for this end point.

End point values	COHORT 12 (ATYPICAL TERATOID RHABDOID TUMOR)
Number of subjects analysed	3
Units: Percentage	0

No statistical analyses for this end point

Primary: Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors

Top of page

End point title

Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors ^[11] ^[12]

End point description

End point type

Primary

End point timeframe

Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[11] - 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: No statistical analysis for this end point.
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this end point.

End point values	COHORT 1 (EWING SARCOMA)	COHORT 5 (NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA)	COHORT 6 (OSTEOSARCOMA)	COHORT 7 (RHABDOMYOSARCOMA)	COHORT 8 (WILMS TUMOR)	COHORT 9 (OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION)	COHORT 10 (OTHER TUMOR TYPES WITHOUT PD-L1 EXPRESSION)	COHORT 11 (RHABDOID TUMOR)
Number of subjects analysed	11	10	10	10	10	4	4	2
Units: Months
median (confidence interval 95%)	1.2 (0.6 to 1.4)	1.3 (1.1 to 1.4)	1.2 (0.7 to 1.8)	1.1 (0.8 to 1.3)	1.3 (1.1 to 1.5)	1.2 (0.7 to 1.3)	1.2 (1.1 to 10.1)	0.7 (0.3 to 1.1)

No statistical analyses for this end point

Primary: PFS as Determined by the Investigator Using mINRC in Participants With Neuroblastoma

Top of page

End point title

PFS as Determined by the Investigator Using mINRC in Participants With Neuroblastoma ^[13] ^[14]

End point description

End point type

Primary

End point timeframe

Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[13] - 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: No statistical analysis for this end point.
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this end point.

End point values	COHORT 3 (NEUROBLASTOMA)
Number of subjects analysed	11
Units: Months
median (confidence interval 95%)	2.6 (1.2 to 4.7)

No statistical analyses for this end point

Primary: PFS as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Top of page

End point title

PFS as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma ^[15] ^[16]

End point description

End point type

Primary

End point timeframe

Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[15] - 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: No statistical analysis for this end point.
[16] - 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: No statistical analysis for this end point.

End point values	COHORT 2 (HODGKIN LYMPHOMA)	COHORT 4 (NON HODGKIN LYMPHOMA)
Number of subjects analysed	9	3 ^[17]
Units: Months
median (confidence interval 95%)	2.8 (2.6 to 4.4)	1.4 (1.1 to 999999)

Notes
[17] - Note: 999999=Not estimable.

No statistical analyses for this end point

Primary: PFS as Determined by the Investigator Using RANO Criteria in Participants With ATRT

Top of page

End point title

PFS as Determined by the Investigator Using RANO Criteria in Participants With ATRT ^[18] ^[19]

End point description

End point type

Primary

End point timeframe

Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[18] - 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: No statistical analysis for this end point.
[19] - 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: No statistical analysis for this end point.

End point values	COHORT 12 (ATYPICAL TERATOID RHABDOID TUMOR)
Number of subjects analysed	3
Units: Months
median (confidence interval 95%)	1.4 (1.4 to 1.7)

No statistical analyses for this end point

Primary: Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest

Top of page

End point title

Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest ^[20]

End point description

End point type

Primary

End point timeframe

From baseline up to approximately 7.5 years

Notes
[20] - 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: No statistical analysis for this end point.

End point values	Atezolizumab
Number of subjects analysed	87
Units: Percentage
number (not applicable)
Adverse Events	97.7
Serious Adverse Events	37.9
Adverse Events of Special Interest	44.8

No statistical analyses for this end point

Primary: Maximum Serum Concentration (Cmax) of Atezolizumab

Top of page

End point title

Maximum Serum Concentration (Cmax) of Atezolizumab ^[21]

End point description

Note: 999999=not available.

End point type

Primary

End point timeframe

Predose (PRD; 0 hours [hr]), 0.5 hr post-infusion (P-I; infusion duration=30-60 minutes) on Day (D) 1 of Cycle (Cy) 1 and 4 (1 Cy=21 days)

Notes
[21] - 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: No statistical analysis for this end point.

End point values	<2 Age (Years)	2 to <12 Age (Years)	12 to <18 Age (Years)	>=18 Age (Years)
Number of subjects analysed	2	26 ^[22]	34 ^[23]	18 ^[24]
Units: ug/mL
geometric mean (geometric coefficient of variation)
Cycle 1	105 ± 6.90	312 ± 28.7	337 ± 26.8	424 ± 26.9
Cycle 4	999999 ± 999999	382 ± 16.4	373 ± 78.9	626 ± 29.2

Notes
[22] - For cycle 4, number of subjects analyzed is 11.
[23] - For cycle 4, number of subjects analyzed is 16.
[24] - For cycle 4, number of subjects analyzed is 6.

No statistical analyses for this end point

Primary: Minimum Serum Concentration (Cmin) of Atezolizumab

Top of page

End point title

Minimum Serum Concentration (Cmin) of Atezolizumab ^[25]

End point description

Note: 999999=not available.

End point type

Primary

End point timeframe

PRD (0 hr) on D1 of Cy2,3,4,8, 12, 16 (1 Cy=21 days) and every 8 cycles thereafter; at any time during visit at study drug discontinuation visit, at least 90 days (maximum 150 days) after the last dose of study drug (up to approximately 7.5 years)

Notes
[25] - 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: No statistical analysis for this end point.

End point values	<2 Age (Years)	2 to <12 Age (Years)	12 to <18 Age (Years)	>=18 Age (Years)
Number of subjects analysed	1	25 ^[26]	32 ^[27]	16 ^[28]
Units: ug/mL
geometric mean (geometric coefficient of variation)
Cycle 2	24.1 ± 999999	59.3 ± 31.4	56.5 ± 50.4	79.9 ± 52.7
Cycle 3	999999 ± 999999	58.9 ± 234.4	85.0 ± 47.4	148 ± 48.9
Cycle 4	999999 ± 999999	99.2 ± 36.4	113 ± 41.1	121 ± 80.4
Cycle 8	999999 ± 999999	166 ± 19.8	145 ± 21.9	209 ± 8.10

Notes
[26] - Cycle(C) 2, number(N) analyzed 25. C3, N analyzed is 13. C4, N analyzed 11. C8, N analyzed 4.
[27] - Cycle(C) 2, number(N) analyzed 32. C3, N analyzed 19. C4, N analyzed 6. C8, N analyzed 4.
[28] - Cycle(C) 2, number(N) analyzed 16. C3, N analyzed 8. C4, N analyzed 6. C8, N analyzed 2.

No statistical analyses for this end point

Primary: Atezolizumab Serum Concentration at Washout

Top of page

End point title

Atezolizumab Serum Concentration at Washout ^[29]

End point description

End point type

Primary

End point timeframe

At least 90 days (maximum 150 days) after last dose of study drug (up to approximately 7.5 years)

Notes
[29] - 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: No statistical analysis for this end point.

End point values	Atezolizumab
Number of subjects analysed	17
Units: ug/mL
geometric mean (geometric coefficient of variation)	1.91 ± 2815.1

No statistical analyses for this end point

Primary: Area Under the Concentration-Time Curve (AUC) of Atezolizumab

Top of page

End point title

Area Under the Concentration-Time Curve (AUC) of Atezolizumab ^[30]

End point description

End point type

Primary

End point timeframe

D1 of Cy1 (1 Cy=21 days)

Notes
[30] - 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: No statistical analysis for this end point.

End point values	<2 Age (Years)	2 to <12 Age (Years)	12 to <18 Age (Years)	>=18 Age (Years)
Number of subjects analysed	2	29	38	18
Units: ugxday/mL
geometric mean (geometric coefficient of variation)	1130 ± 5.28	2209 ± 21.3	2816 ± 17.7	3579 ± 28.4

No statistical analyses for this end point

Primary: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab

Top of page

End point title

Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab ^[31]

End point description

End point type

Primary

End point timeframe

PRD (0 hr) on D1 of Cy1,2,3,4,8,12,16 (1 Cy=21 days) & every 8 cycles thereafter; at any time during visit on Cy1D8, study drug discontinuation, at least 90 days (maximum 150 days) after last dose of study drug (up to approximately 7.5 years)

Notes
[31] - 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: No statistical analysis for this end point.

End point values	Atezolizumab
Number of subjects analysed	78
Units: Percentage
number (not applicable)
Baseline	2.6
Post-baseline	14.3

No statistical analyses for this end point

Secondary: Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 Criteria in Participants With Solid Tumors

Top of page

End point title

Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 Criteria in Participants With Solid Tumors ^[32]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[32] - 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: No statistical analysis for this end point.

End point values	COHORT 1 (EWING SARCOMA)	COHORT 5 (NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA)	COHORT 6 (OSTEOSARCOMA)	COHORT 7 (RHABDOMYOSARCOMA)	COHORT 8 (WILMS TUMOR)	COHORT 9 (OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION)	COHORT 10 (OTHER TUMOR TYPES WITHOUT PD-L1 EXPRESSION)	COHORT 11 (RHABDOID TUMOR)
Number of subjects analysed	0 ^[33]	1 ^[34]	0 ^[35]	0 ^[36]	0 ^[37]	0 ^[38]	0 ^[39]	0 ^[40]
Units: Months
median (confidence interval 95%)	( to )	13.2 (000000 to 999999)	( to )	( to )	( to )	( to )	( to )	( to )

Notes
[33] - There was no objective response.
[34] - Note: 000000=not estimable. 9999999= not estimable. There was only 1 participant.
[35] - There was no objective response.
[36] - There was no objective response.
[37] - There was no objective response.
[38] - There was no objective response.
[39] - There was no objective response.
[40] - There was no objective response.

No statistical analyses for this end point

Secondary: DOR as Determined by the Investigator Using mINRC in Participants With Neuroblastoma

Top of page

End point title

DOR as Determined by the Investigator Using mINRC in Participants With Neuroblastoma ^[41]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[41] - 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: No statistical analysis for this end point.

End point values	COHORT 3 (NEUROBLASTOMA)
Number of subjects analysed	0 ^[42]
Units: Months
median (confidence interval 95%)	( to )

Notes
[42] - No subjects had an objective response.

No statistical analyses for this end point

Secondary: DOR as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Top of page

End point title

DOR as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma ^[43]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[43] - 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: No statistical analysis for this end point.

End point values	COHORT 2 (HODGKIN LYMPHOMA)	COHORT 4 (NON HODGKIN LYMPHOMA)
Number of subjects analysed	2 ^[44]	1 ^[45]
Units: Months
median (confidence interval 95%)	999999 (4.1 to 999999)	999999 (999999 to 999999)

Notes
[44] - Note: 999999= not estimable. Only 1 participants without an event.
[45] - Note: 999999= not estimable. Only 1 participants without an event.

No statistical analyses for this end point

Secondary: DOR as Determined by the Investigator Using RANO Criteria in Participants With ATRT

Top of page

End point title

DOR as Determined by the Investigator Using RANO Criteria in Participants With ATRT ^[46]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[46] - 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: No statistical analysis for this end point.

End point values	COHORT 12 (ATYPICAL TERATOID RHABDOID TUMOR)
Number of subjects analysed	0 ^[47]
Units: Months
median (confidence interval 95%)	( to )

Notes
[47] - No subjects had an objective response.

No statistical analyses for this end point

Secondary: Overall Survival (OS)

Top of page

End point title

Overall Survival (OS)

End point description

End point type

Secondary

End point timeframe

Baseline until death (up to approximately 7.5 years)

End point values	Atezolizumab
Number of subjects analysed	87
Units: Months
median (confidence interval 95%)	7.4 (5.3 to 9.6)

No statistical analyses for this end point

Secondary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors

Top of page

End point title

Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors ^[48]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[48] - 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: No statistical analysis for this end point.

End point values	COHORT 1 (EWING SARCOMA)	COHORT 5 (NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA)	COHORT 6 (OSTEOSARCOMA)	COHORT 7 (RHABDOMYOSARCOMA)	COHORT 8 (WILMS TUMOR)	COHORT 9 (OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION)	COHORT 10 (OTHER TUMOR TYPES WITHOUT PD-L1 EXPRESSION)	COHORT 11 (RHABDOID TUMOR)	COHORT 12 (ATYPICAL TERATOID RHABDOID TUMOR)
Number of subjects analysed	0 ^[49]	0 ^[50]	0 ^[51]	0 ^[52]	0 ^[53]	0 ^[54]	0 ^[55]	0 ^[56]	0 ^[57]
Units: Percentage

Notes
[49] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[50] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[51] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[52] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[53] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[54] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[55] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[56] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[57] - Analysis not conducted due to limited objective responses using primary evaluation criteria.

No statistical analyses for this end point

Secondary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Related Response Criteria (irRC) for Participants With Neuroblastoma

Top of page

End point title

Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Related Response Criteria (irRC) for Participants With Neuroblastoma ^[58]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[58] - 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: No statistical analysis for this end point.

End point values	COHORT 3 (NEUROBLASTOMA)
Number of subjects analysed	0 ^[59]
Units: Percentage

Notes
[59] - Analysis not conducted due to limited objective responses using primary evaluation criteria.

No statistical analyses for this end point

Secondary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using irRC for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Top of page

End point title

Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using irRC for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma ^[60]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[60] - 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: No statistical analysis for this end point.

End point values	COHORT 2 (HODGKIN LYMPHOMA)	COHORT 4 (NON HODGKIN LYMPHOMA)
Number of subjects analysed	0 ^[61]	0 ^[62]
Units: Percentage

Notes
[61] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[62] - Analysis not conducted due to limited objective responses using primary evaluation criteria.

No statistical analyses for this end point

Secondary: PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors

Top of page

End point title

PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors ^[63]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[63] - 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: No statistical analysis for this end point.

End point values	COHORT 1 (EWING SARCOMA)	COHORT 5 (NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA)	COHORT 6 (OSTEOSARCOMA)	COHORT 7 (RHABDOMYOSARCOMA)	COHORT 8 (WILMS TUMOR)	COHORT 9 (OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION)	COHORT 10 (OTHER TUMOR TYPES WITHOUT PD-L1 EXPRESSION)	COHORT 11 (RHABDOID TUMOR)	COHORT 12 (ATYPICAL TERATOID RHABDOID TUMOR)
Number of subjects analysed	0 ^[64]	0 ^[65]	0 ^[66]	0 ^[67]	0 ^[68]	0 ^[69]	0 ^[70]	0 ^[71]	0 ^[72]
Units: Months
median (confidence interval 95%)	( to )	( to )	( to )	( to )	( to )	( to )	( to )	( to )	( to )

Notes
[64] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[65] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[66] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[67] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[68] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[69] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[70] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[71] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[72] - Analysis not conducted due to limited objective responses using primary evaluation criteria.

No statistical analyses for this end point

Secondary: PFS as Determined by the Investigator Using irRC for Participants With Neuroblastoma

Top of page

End point title

PFS as Determined by the Investigator Using irRC for Participants With Neuroblastoma ^[73]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[73] - 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: No statistical analysis for this end point.

End point values	COHORT 3 (NEUROBLASTOMA)
Number of subjects analysed	0 ^[74]
Units: Months
median (confidence interval 95%)	( to )

Notes
[74] - Analysis not conducted due to limited objective responses using primary evaluation criteria.

No statistical analyses for this end point

Secondary: PFS as Determined by the Investigator Using irRC for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Top of page

End point title

PFS as Determined by the Investigator Using irRC for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma ^[75]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[75] - 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: No statistical analysis for this end point.

End point values	COHORT 2 (HODGKIN LYMPHOMA)	COHORT 4 (NON HODGKIN LYMPHOMA)
Number of subjects analysed	0 ^[76]	0 ^[77]
Units: Months
median (confidence interval 95%)	( to )	( to )

Notes
[76] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[77] - Analysis not conducted due to limited objective responses using primary evaluation criteria.

No statistical analyses for this end point

Secondary: DOR as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors

Top of page

End point title

DOR as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors ^[78]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[78] - 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: No statistical analysis for this end point.

End point values	COHORT 1 (EWING SARCOMA)	COHORT 5 (NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA)	COHORT 6 (OSTEOSARCOMA)	COHORT 7 (RHABDOMYOSARCOMA)	COHORT 8 (WILMS TUMOR)	COHORT 9 (OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION)	COHORT 10 (OTHER TUMOR TYPES WITHOUT PD-L1 EXPRESSION)	COHORT 11 (RHABDOID TUMOR)	COHORT 12 (ATYPICAL TERATOID RHABDOID TUMOR)
Number of subjects analysed	0 ^[79]	0 ^[80]	0 ^[81]	0 ^[82]	0 ^[83]	0 ^[84]	0 ^[85]	0 ^[86]	0 ^[87]
Units: Months

Notes
[79] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[80] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[81] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[82] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[83] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[84] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[85] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[86] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[87] - Analysis not conducted due to limited objective responses using primary evaluation criteria.

No statistical analyses for this end point

Secondary: DOR as Determined by the Investigator Using irRC for Participants With Neuroblastoma

Top of page

End point title

DOR as Determined by the Investigator Using irRC for Participants With Neuroblastoma ^[88]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[88] - 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: No statistical analysis for this end point.

End point values	COHORT 3 (NEUROBLASTOMA)
Number of subjects analysed	0 ^[89]
Units: Percentage
median (confidence interval 95%)	( to )

Notes
[89] - Analysis not conducted due to limited objective responses using primary evaluation criteria.

No statistical analyses for this end point

Secondary: DOR as Determined by the Investigator Using irRC for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Top of page

End point title

DOR as Determined by the Investigator Using irRC for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma ^[90]

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 7.5 years)

Notes
[90] - 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: No statistical analysis for this end point.

End point values	COHORT 2 (HODGKIN LYMPHOMA)	COHORT 4 (NON HODGKIN LYMPHOMA)
Number of subjects analysed	0 ^[91]	0 ^[92]
Units: Months
median (confidence interval 95%)	( to )	( to )

Notes
[91] - Analysis not conducted due to limited objective responses using primary evaluation criteria.
[92] - Analysis not conducted due to limited objective responses using primary evaluation criteria.

No statistical analyses for this end point

Secondary: Optimal Dose of Atezolizumab in Pediatric and Young Adult Participants

Top of page

End point title

Optimal Dose of Atezolizumab in Pediatric and Young Adult Participants

End point description

Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.

End point type

Secondary

End point timeframe

From baseline up to approximately 7.5 years

End point values	Atezolizumab
Number of subjects analysed	87
Units: 15mg/kg for <18 age, 1200mg for>=18 age
<18 Age (Years)	15
>=18 Age (Years)	1200

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From baseline up to approximately 7.5 years

Adverse event reporting additional description

Adverse Events reporting is for the Safety Evaluable Population, defined as patients who received any amount of any component of study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

COHORT 1

Reporting group description

EWING SARCOMA

Reporting group title

COHORT 2

Reporting group description

HODGKIN LYMPHOMA

Reporting group title

COHORT 3

Reporting group description

NEUROBLASTOMA

Reporting group title

COHORT 4

Reporting group description

NON HODGKIN LYMPHOMA

Reporting group title

COHORT 5

Reporting group description

NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA;

Reporting group title

COHORT 6

Reporting group description

OSTEOSARCOMA

Reporting group title

COHORT 7

Reporting group description

RHABDOMYOSARCOMA

Reporting group title

COHORT 8

Reporting group description

WILMS TUMOR

Reporting group title

COHORT 9

Reporting group description

OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION

Reporting group title

COHORT 10

Reporting group description

OTHER TUMOR TYPES WITHOUT DOCUMENTED PD-L1 EXPRESSION

Reporting group title

COHORT 11

Reporting group description

RHABDOID TUMOR

Reporting group title

COHORT 12

Reporting group description

ATYPICAL TERATOID RHABDOID TUMOR

COHORT 1

COHORT 2

COHORT 3

COHORT 4

COHORT 5

COHORT 6

COHORT 7

COHORT 8

COHORT 9

COHORT 10

COHORT 11

COHORT 12

Total subjects affected by serious adverse events

subjects affected / exposed

4 / 11 (36.36%)

3 / 9 (33.33%)

2 / 11 (18.18%)

0 / 3 (0.00%)

3 / 10 (30.00%)

6 / 10 (60.00%)

3 / 10 (30.00%)

5 / 10 (50.00%)

2 / 4 (50.00%)

3 / 4 (75.00%)

1 / 2 (50.00%)

1 / 3 (33.33%)

number of deaths (all causes)

number of deaths resulting from adverse events

Vascular disorders

SHOCK HAEMORRHAGIC

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SUPERIOR VENA CAVA SYNDROME

subjects affected / exposed

1 / 11 (9.09%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

CHEST PAIN

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

2 / 10 (20.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

FATIGUE

subjects affected / exposed

1 / 11 (9.09%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PAIN

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PYREXIA

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

1 / 11 (9.09%)

0 / 3 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

2 / 10 (20.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

GRAFT VERSUS HOST DISEASE

subjects affected / exposed

0 / 11 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Respiratory, thoracic and mediastinal disorders

DYSPNOEA

subjects affected / exposed

0 / 11 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PLEURAL EFFUSION

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

PNEUMOTHORAX

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

AGITATION

subjects affected / exposed

0 / 11 (0.00%)

1 / 9 (11.11%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

POSTOPERATIVE HYPOTENSION

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

TOXICITY TO VARIOUS AGENTS

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

HEADACHE

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HYDROCEPHALUS

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 3 (33.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

PARAESTHESIA

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

VITH NERVE DISORDER

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

ANAEMIA

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FEBRILE NEUTROPENIA

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

PAPILLOEDEMA

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

ABDOMINAL DISTENSION

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CONSTIPATION

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LARGE INTESTINAL OBSTRUCTION

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PANCREATITIS

subjects affected / exposed

1 / 11 (9.09%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

UPPER GASTROINTESTINAL HAEMORRHAGE

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

CHOLESTASIS

subjects affected / exposed

1 / 11 (9.09%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

PRURITUS

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RASH MACULO-PAPULAR

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

TOXIC SKIN ERUPTION

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

HYDRONEPHROSIS

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

URINARY TRACT OBSTRUCTION

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

BONE PAIN

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

FLANK PAIN

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

ABDOMINAL ABSCESS

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DEVICE RELATED INFECTION

subjects affected / exposed

1 / 11 (9.09%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

INCISION SITE ABSCESS

subjects affected / exposed

1 / 11 (9.09%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

LUNG INFECTION

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

1 / 2 (50.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

POSTOPERATIVE ABSCESS

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

PYELONEPHRITIS

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

RESPIRATORY TRACT INFECTION

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SEPTIC SHOCK

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

1 / 11 (9.09%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

STAPHYLOCOCCAL SEPSIS

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

URINARY TRACT INFECTION

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

DEHYDRATION

subjects affected / exposed

1 / 11 (9.09%)

0 / 9 (0.00%)

1 / 11 (9.09%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

DIABETIC KETOACIDOSIS

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HYPONATRAEMIA

subjects affected / exposed

0 / 11 (0.00%)

0 / 9 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	COHORT 1	COHORT 2	COHORT 3	COHORT 4	COHORT 5	COHORT 6	COHORT 7	COHORT 8	COHORT 9	COHORT 10	COHORT 11	COHORT 12
Total subjects affected by non serious adverse events
subjects affected / exposed	11 / 11 (100.00%)	8 / 9 (88.89%)	11 / 11 (100.00%)	3 / 3 (100.00%)	10 / 10 (100.00%)	10 / 10 (100.00%)	10 / 10 (100.00%)	10 / 10 (100.00%)	4 / 4 (100.00%)	3 / 4 (75.00%)	2 / 2 (100.00%)	2 / 3 (66.67%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR INFLAMMATION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0
TUMOUR PAIN
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	0	1	0	2	0	0	0	0	0
Vascular disorders
EMBOLISM
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
HOT FLUSH
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
HYPERTENSION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	1	1	0	0	1	0	0	0
HYPOTENSION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	0	0
HYPOVOLAEMIC SHOCK
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0
VENOUS THROMBOSIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
Surgical and medical procedures
CENTRAL VENOUS CATHETERISATION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
General disorders and administration site conditions
ASTHENIA
subjects affected / exposed	1 / 11 (9.09%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0	1	2	1	0	0	0	0	0
AXILLARY PAIN
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0
CATHETER SITE ERYTHEMA
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0
CHEST DISCOMFORT
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0
CHEST PAIN
subjects affected / exposed	1 / 11 (9.09%)	1 / 9 (11.11%)	1 / 11 (9.09%)	0 / 3 (0.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	1	0	1	5	0	2	0	0	0	0
CHILLS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0
FACE OEDEMA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	0	0
FATIGUE
subjects affected / exposed	2 / 11 (18.18%)	2 / 9 (22.22%)	3 / 11 (27.27%)	0 / 3 (0.00%)	4 / 10 (40.00%)	6 / 10 (60.00%)	3 / 10 (30.00%)	6 / 10 (60.00%)	1 / 4 (25.00%)	2 / 4 (50.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)
occurrences all number	3	2	3	0	13	6	3	7	1	2	0	1
GENERALISED OEDEMA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
INFLUENZA LIKE ILLNESS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	2	0	0	2	1	0	0	0	0	0
MALAISE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0
NON-CARDIAC CHEST PAIN
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0	0
OEDEMA
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0
OEDEMA PERIPHERAL
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	1	0	1	0	1	0	0
PAIN
subjects affected / exposed	2 / 11 (18.18%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	2	1	0	0	2	0	0	2	0	0	0	0
PERIPHERAL SWELLING
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0
PYREXIA
subjects affected / exposed	3 / 11 (27.27%)	3 / 9 (33.33%)	4 / 11 (36.36%)	2 / 3 (66.67%)	2 / 10 (20.00%)	8 / 10 (80.00%)	5 / 10 (50.00%)	4 / 10 (40.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	5	9	5	2	5	14	6	5	2	1	0	0
THIRST
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0
VACCINATION SITE OEDEMA
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
Reproductive system and breast disorders
PELVIC PAIN
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0
VAGINAL DISCHARGE
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
VAGINAL HAEMORRHAGE
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
CATARRH
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
COUGH
subjects affected / exposed	3 / 11 (27.27%)	4 / 9 (44.44%)	2 / 11 (18.18%)	1 / 3 (33.33%)	1 / 10 (10.00%)	5 / 10 (50.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	2 / 4 (50.00%)	1 / 4 (25.00%)	1 / 2 (50.00%)	1 / 3 (33.33%)
occurrences all number	4	14	2	1	1	8	0	1	2	1	1	1
DYSPHONIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	1	0	0
DYSPNOEA
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	1	0	2	0	1	0	0	0	0
DYSPNOEA EXERTIONAL
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
EPISTAXIS
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	0	0	0
HYPOXIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0
IRREGULAR BREATHING
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
LARYNGEAL INFLAMMATION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0
NASAL CONGESTION
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	2 / 11 (18.18%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	2	0	0	2	0	0	0	0	0	0
DISORDER OROPHARYNGEAL PAIN
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
PHARYNGEAL INFLAMMATION
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
PLEURAL EFFUSION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	0
PNEUMONITIS
subjects affected / exposed	0 / 11 (0.00%)	2 / 9 (22.22%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0
RHINITIS ALLERGIC
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0
STRIDOR
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
TACHYPNOEA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0
ATELECTASIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
OBSTRUCTIVE AIRWAYS DISORDER
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
OROPHARYNGEAL PAIN
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0
RHINORRHOEA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0	0
Psychiatric disorders
AGITATION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
ANXIETY
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	0	1	1	0	0	1	0	0	0
BRUXISM
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0
CONFUSIONAL STATE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0
DELIRIUM
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
DEPRESSION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
INSOMNIA
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	1	1	0	1	1	1	0	0
IRRITABILITY
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	4	0	0	0	0	0	0	0
SLEEP DISORDER
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
ABNORMAL BEHAVIOUR
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0
Product issues
DEVICE BREAKAGE
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	1 / 11 (9.09%)	1 / 9 (11.11%)	3 / 11 (27.27%)	0 / 3 (0.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	3	3	0	1	3	0	1	1	0	0	0
AMYLASE INCREASED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	2	0	1	0	0	0	0	0
ANTITHROMBIN III DECREASED
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	4 / 11 (36.36%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	3	4	0	0	2	0	4	1	0	0	0
BLOOD ALKALINE PHOSPHATASE INCREASED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
BLOOD BILIRUBIN INCREASED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	0
BLOOD CHLORIDE DECREASED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
BLOOD CREATININE INCREASED
subjects affected / exposed	2 / 11 (18.18%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	3 / 10 (30.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	2	0	0	0	1	0	0	3	0	1	0	0
BLOOD LACTATE DEHYDROGENASE INCREASED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0
BLOOD POTASSIUM DECREASED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
BLOOD THYROID STIMULATING HORMONE INCREASED
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	2	0	0	0	0	0	0	0
BLOOD URINE PRESENT
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
C-REACTIVE PROTEIN INCREASED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	0	0
CANDIDA TEST POSITIVE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
CARDIAC MURMUR
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0
GAMMA-GLUTAMYLTRANSFERASE INCREASED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
INTERNATIONAL NORMALISED RATIO INCREASED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
LIPASE INCREASED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	0	0
LYMPHOCYTE COUNT DECREASED
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	2 / 10 (20.00%)	3 / 10 (30.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	0	4	6	0	5	1	0	0	0
NEUTROPHIL COUNT DECREASED
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	0	0	0	4	3	0	5	0	0	0	1
NOROVIRUS TEST POSITIVE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
OXYGEN SATURATION DECREASED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0
PLATELET COUNT DECREASED
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	3	3	0	4	1	0	0	0
PROTHROMBIN LEVEL DECREASED
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0
VITAMIN K DECREASED
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
WEIGHT DECREASED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	1 / 3 (33.33%)	2 / 10 (20.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	1	2	1	1	2	0	0	0	0
WHITE BLOOD CELL COUNT DECREASED
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	2 / 11 (18.18%)	0 / 3 (0.00%)	2 / 10 (20.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)
occurrences all number	2	0	2	0	3	4	0	4	1	0	0	1
Injury, poisoning and procedural complications
ARTHROPOD BITE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0
FALL
subjects affected / exposed	1 / 11 (9.09%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0	2	0	0	1	0	0	0	0
LIMB INJURY
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0
POST PROCEDURAL SWELLING
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0
PROCEDURAL PAIN
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0
THERMAL BURN
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0
UROSTOMY COMPLICATION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0
WOUND DEHISCENCE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
CONTUSION
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	0	0	0
Congenital, familial and genetic disorders
FANCONI SYNDROME
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
Cardiac disorders
PERICARDIAL EFFUSION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0
SINUS TACHYCARDIA
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	2	0	0	0	0
TACHYCARDIA
subjects affected / exposed	1 / 11 (9.09%)	1 / 9 (11.11%)	0 / 11 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	1	1	1	2	1	1	0	0	0
Nervous system disorders
AMPUTATION STUMP PAIN
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
DYSGEUSIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0
HEADACHE
subjects affected / exposed	2 / 11 (18.18%)	1 / 9 (11.11%)	3 / 11 (27.27%)	1 / 3 (33.33%)	2 / 10 (20.00%)	2 / 10 (20.00%)	2 / 10 (20.00%)	3 / 10 (30.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)
occurrences all number	2	8	3	1	3	8	2	5	0	0	0	2
HYPOAESTHESIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	2	0	0	0	0	0
MIGRAINE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
MIGRAINE WITH AURA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
NEURALGIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	2	1	0	0	0	0
PARAESTHESIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0
PHANTOM LIMB SYNDROME
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
SEIZURE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0
SOMNOLENCE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
TREMOR
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
DIZZINESS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 4 (50.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0	2	0	0	0
PARAPARESIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	3 / 11 (27.27%)	1 / 9 (11.11%)	3 / 11 (27.27%)	1 / 3 (33.33%)	5 / 10 (50.00%)	2 / 10 (20.00%)	3 / 10 (30.00%)	2 / 10 (20.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 2 (50.00%)	1 / 3 (33.33%)
occurrences all number	4	1	6	1	12	2	3	2	1	1	1	1
FEBRILE NEUTROPENIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0
LEUKOPENIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
LYMPHADENOPATHY
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	2	0	0	0	0	0	0	0
LYMPHOPENIA
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	2	0	0	1	0	0	0	0
NEUTROPENIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0
THROMBOCYTOPENIA
subjects affected / exposed	2 / 11 (18.18%)	2 / 9 (22.22%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	3	2	1	0	0	0	0	2	0	1	0	0
THROMBOCYTOSIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0
Ear and labyrinth disorders
EAR PAIN
subjects affected / exposed	1 / 11 (9.09%)	2 / 9 (22.22%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	3	0	0	0	0	0	0	0	0	0	0
VERTIGO
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
Eye disorders
ECZEMA EYELIDS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
EYELID PTOSIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0
OPSOCLONUS MYOCLONUS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0
PERIORBITAL OEDEMA
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
PHOTOPHOBIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	3	0	0	0	0	0	0	0
PHOTOPSIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
VISION BLURRED
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1
Gastrointestinal disorders
ABDOMINAL PAIN
subjects affected / exposed	3 / 11 (27.27%)	2 / 9 (22.22%)	2 / 11 (18.18%)	0 / 3 (0.00%)	2 / 10 (20.00%)	3 / 10 (30.00%)	1 / 10 (10.00%)	3 / 10 (30.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)
occurrences all number	3	2	2	0	4	3	1	5	0	0	0	1
ABDOMINAL PAIN LOWER
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	2	0	0	0	0	0	1	0	0	0	0
ABDOMINAL PAIN UPPER
subjects affected / exposed	1 / 11 (9.09%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0
ANAL INCONTINENCE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
ASCITES
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
COLITIS
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0
CONSTIPATION
subjects affected / exposed	3 / 11 (27.27%)	1 / 9 (11.11%)	2 / 11 (18.18%)	1 / 3 (33.33%)	6 / 10 (60.00%)	6 / 10 (60.00%)	2 / 10 (20.00%)	6 / 10 (60.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	6	1	2	1	6	7	2	7	1	0	0	0
DENTAL CARIES
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0	0
DIARRHOEA
subjects affected / exposed	0 / 11 (0.00%)	2 / 9 (22.22%)	4 / 11 (36.36%)	0 / 3 (0.00%)	4 / 10 (40.00%)	4 / 10 (40.00%)	2 / 10 (20.00%)	2 / 10 (20.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	3	5	0	6	5	3	2	1	1	0	0
DYSPEPSIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
DYSPHAGIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
ENTEROCOLITIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
HAEMATOCHEZIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	0	0
LIP ULCERATION
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
NAUSEA
subjects affected / exposed	4 / 11 (36.36%)	1 / 9 (11.11%)	1 / 11 (9.09%)	0 / 3 (0.00%)	2 / 10 (20.00%)	4 / 10 (40.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	4	3	2	0	2	7	0	2	2	0	0	0
NONINFECTIVE GINGIVITIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
ODYNOPHAGIA
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0
ORAL PAIN
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
PROCTALGIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	0
RECTAL DISCHARGE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0
STOMATITIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	1	0	1	0	0	0	0
SUBILEUS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
SWOLLEN TONGUE
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0
UPPER GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
VOMITING
subjects affected / exposed	3 / 11 (27.27%)	3 / 9 (33.33%)	2 / 11 (18.18%)	0 / 3 (0.00%)	3 / 10 (30.00%)	3 / 10 (30.00%)	1 / 10 (10.00%)	4 / 10 (40.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	4	6	2	0	5	4	2	5	2	1	0	0
Hepatobiliary disorders
HYPERBILIRUBINAEMIA
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	1	1	1	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
ALOPECIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
BLISTER
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
DERMATITIS
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0
DERMATITIS CONTACT
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0
DRY SKIN
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	1 / 11 (9.09%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	2	1	2	0	0	0	0	0	0	0	0
ECZEMA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	0
ERYTHEMA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0
HYPERHIDROSIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	3	1	0	0	0	0	0
PALMAR-PLANTAR
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
ERYTHRODYSAESTHESIA SYNDROME
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0
PERIORAL DERMATITIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0
PETECHIAE
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
PITYRIASIS ROSEA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
PRURITUS
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	2 / 10 (20.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	1	2	1	1	1	0	0	0	0
RASH
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	0	0
RASH MACULO-PAPULAR
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	1	1	0	0	0	0	0	0
RASH PRURITIC
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0
SKIN DISCOLOURATION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
URTICARIA
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0
Renal and urinary disorders
ACUTE KIDNEY INJURY
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
DYSURIA
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	2	0	0	0	0
GLYCOSURIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
HAEMATURIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	0	0
HYDRONEPHROSIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0
NEPHROLITHIASIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
OLIGURIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
PROTEINURIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0
URINARY INCONTINENCE
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0
URINARY RETENTION
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	0	0	1	0	1	0	0	0	0
Endocrine disorders
HYPERTHYROIDISM
subjects affected / exposed	0 / 11 (0.00%)	2 / 9 (22.22%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	3	0	0	0	0	0	0	0	0	0	0
HYPOTHYROIDISM
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	1 / 11 (9.09%)	1 / 9 (11.11%)	2 / 11 (18.18%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	2	0	1	1	1	1	0	2	0	0
BACK PAIN
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	2 / 11 (18.18%)	0 / 3 (0.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	0	3	0	2	4	1	2	0	1	0	2
FLANK PAIN
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	1	0	0	1	0	0	0	0
HAEMARTHROSIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
MUSCLE SPASMS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0
MUSCULOSKELETAL PAIN
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	2	1	0	0	0	0	0	0
MYALGIA
subjects affected / exposed	1 / 11 (9.09%)	1 / 9 (11.11%)	1 / 11 (9.09%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	1	0	1	0	1	0	0	0	0	0
NECK PAIN
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	2 / 11 (18.18%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	2	0	1	0	0	1	0	2	0	0
PAIN IN EXTREMITY
subjects affected / exposed	2 / 11 (18.18%)	1 / 9 (11.11%)	2 / 11 (18.18%)	0 / 3 (0.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	2 / 4 (50.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	4	2	2	0	2	3	0	0	1	3	0	0
PAIN IN JAW
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	2	0	0	0	0	0
JOINT SWELLING
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0
Infections and infestations
BACTERAEMIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
BRONCHITIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
CANDIDA URETHRITIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
CONJUNCTIVITIS
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0	0
DERMATOPHYTOSIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0
DEVICE RELATED INFECTION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0
FUNGAL SKIN INFECTION
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
GENITAL HERPES
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
HERPES VIRUS INFECTION
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0	0	0	0	0
INFLUENZA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	3	0	0	0	0	0	0	0
LARYNGITIS
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0
LUNG INFECTION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0
NASOPHARYNGITIS
subjects affected / exposed	1 / 11 (9.09%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0	0	0	1	2	0	0	0	0
ORAL CANDIDIASIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0
ORAL HERPES
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0
PARONYCHIA
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
PHARYNGITIS
subjects affected / exposed	0 / 11 (0.00%)	2 / 9 (22.22%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	2	0	1	0	2	0	0	0	1	0	0
PYELONEPHRITIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0
RHINITIS
subjects affected / exposed	0 / 11 (0.00%)	4 / 9 (44.44%)	2 / 11 (18.18%)	1 / 3 (33.33%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	16	2	1	1	2	0	1	0	0	0	0
SKIN INFECTION
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0	0
STAPHYLOCOCCAL
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0
TONSILLITIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0	0	1	0	0	1	0	0	0
URINARY TRACT INFECTION
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0
VASCULAR DEVICE INFECTION
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0
VULVITIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
DECREASED APPETITE
subjects affected / exposed	4 / 11 (36.36%)	1 / 9 (11.11%)	2 / 11 (18.18%)	0 / 3 (0.00%)	2 / 10 (20.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	4 / 10 (40.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 3 (0.00%)
occurrences all number	4	1	2	0	4	2	1	5	1	0	1	0
DEHYDRATION
subjects affected / exposed	2 / 11 (18.18%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	1	0	0
HYPERGLYCAEMIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0
HYPERKALAEMIA
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	0	1	0	0	0	1	0	0	0
HYPERNATRAEMIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0
HYPERTRIGLYCERIDAEMIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0
HYPERURICAEMIA
subjects affected / exposed	0 / 11 (0.00%)	1 / 9 (11.11%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0
HYPOALBUMINAEMIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0
HYPOCALCAEMIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0
HYPOKALAEMIA
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	0	1	3	0	0	0	2	0	0
HYPOMAGNESAEMIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	1	4	0	0	0	0
HYPONATRAEMIA
subjects affected / exposed	1 / 11 (9.09%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	3 / 10 (30.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	0	0	1	0	3	1	0	0	0
HYPOPHOSPHATAEMIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	2	0	0	0
METABOLIC ACIDOSIS
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0
HYPERMAGNESAEMIA
subjects affected / exposed	0 / 11 (0.00%)	0 / 9 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	3	0	0	0	1	4	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

08 May 2015

Protocol was amended to include the following updates and clarification: There was an update to acceptable methods of contraception. Inclusion criteria were modified to include only children or young adults with tumor types that are known or expected to have PD-L1 pathway involvement. Patients being treated beyond radiologic progression were allowed to continue study drug treatment for 2 years. If a patient continued to experience clinical benefit beyond 2 years, the Sponsor could apply for additional approval from health authorities. The safety follow-up period was extended to 90 days. The initial dose of atezolizumab was changed to 15 mg/kg for all patients <18 years of age. Study drug treatment duration was changed to a maximum of 8 months. Patients continuing to experience clinical benefit at 8 months could continue study drug treatment with approval of the Medical Monitor. Pharmacokinetic outcome measures were modified to include blood draws during Cycle 4. Clarification made included: the first 5 patients had to be >= 2 years of age to ensure the safety and tolerability of children <2 years. There had to be at least 24 hours between the initial study drug doses of the first 5 patients. There had to also be at least 24 hours between study drug doses for the first 3 patients in each tumor type. Dosage information was modified to include patients <6 years. Clarifications regarding the timing of scheduled visits and assessments (every 6 weeks after Cycle 8) and thyroid testing (every 6 weeks throughout study). The endpoint for osteosarcoma was changed to CBRR, which was defined as percentage of patients who had an objective response or stable disease for at least 6 months. The exclusion criteria for lymphoma patients were modified to exclude patients with CNS lymphoma or leptomeningeal disease. The inclusion/exclusion criteria pertaining to CNS metastases were clarified.

15 Oct 2015

Protocol was amended to include the following clarifications: Management of gastrointestinal, dermatologic, pulmonary toxicity, hepatotoxicity, potential pancreatic or eye toxicity, and other immune-mediated adverse events was updated. Recommendations for early identification and management of systemic immune activation were updated. Clarification was added to specify that patients should not receive a live or live attenuated vaccine during study drug treatment and for 90 days following the last dose of atezolizumab. Clarification was added regarding the total amount of blood draw volume. Guidance was amended to specify that atezolizumab could continue while receiving radiation and the selection of lesions for radiation was clarified. Pregnancy testing was revised to be mandatory prior to every cycle for all female patients who have reached menarche. The number of patients to be enrolled in a tumor type cohort was set at a maximum of 40 patients in order to limit exposure to drugs with unclear efficacy.

21 Oct 2016

Protocol was amended to include the following key changes: INRC used in this study was modified from the original INRC publications; notations were added to the protocol to clarify the definition of measurable (evaluable) disease on CT and MRI scans for malignant lymph nodes. The protocol was modified to include patients with ATRT and RT based on significant clinical response seen in a patient in the non-rhabdomyosarcoma soft tissue sarcoma cohort. The safety monitoring and reporting period was clarified for SAEs, AESIs, and all other AEs in order to better focus on the most relevant safety information and to be consistent with the atezolizumab program in adult studies. The criterion excluding patients under treatment with investigational therapy (except specific cancer therapies) within 4 weeks prior to initiation of study drug was modified as the duration could be considered extensive in this impaired patient population. If required, patients could be evaluated on the basis of their grade of recovery of toxicity. The exclusion criterion referring to non-hematologic toxicity was modified to specify that long-term sequelae of prior treatment were not to be considered non-hematologic toxicity, but instead were required to be considered chronic medical conditions. The timing of various treatments prior to initiation of study drug treatment as specified in the exclusion criteria were amended. In addition, the study eligibility criteria were amended to allow enrollment of patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and patients with controlled Type 1 diabetes mellitus on stable insulin regimen.

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: An Early-Phase, Multicenter, Open-Label Study of the Safety and Pharmacokinetics of Atezolizumab (MPDL3280A) In Pediatric and Young Adult Patients With Previously Treated Solid Tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Participants With Solid Tumors

Primary: Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Participants With Solid Tumors

Primary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Primary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Primary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Modified International Neuroblastoma Response Criteria (mINRC) in Participants With Neuroblastoma

Primary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Modified International Neuroblastoma Response Criteria (mINRC) in Participants With Neuroblastoma

Primary: Percentage of Participants With Clinical Benefit as Determined by the Investigator According to RECIST v1.1 Criteria in Participants With Osteosarcoma

Primary: Percentage of Participants With Clinical Benefit as Determined by the Investigator According to RECIST v1.1 Criteria in Participants With Osteosarcoma

Primary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Response Assessment in Neuro-Oncology (RANO) Criteria in Participants With Atypical Teratoid Rhabdoid Tumor (ATRT)

Primary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Response Assessment in Neuro-Oncology (RANO) Criteria in Participants With Atypical Teratoid Rhabdoid Tumor (ATRT)

Primary: Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors

Primary: Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors

Primary: PFS as Determined by the Investigator Using mINRC in Participants With Neuroblastoma

Primary: PFS as Determined by the Investigator Using mINRC in Participants With Neuroblastoma

Primary: PFS as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Primary: PFS as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Primary: PFS as Determined by the Investigator Using RANO Criteria in Participants With ATRT

Primary: PFS as Determined by the Investigator Using RANO Criteria in Participants With ATRT

Primary: Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest

Primary: Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest

Primary: Maximum Serum Concentration (Cmax) of Atezolizumab

Primary: Maximum Serum Concentration (Cmax) of Atezolizumab

Primary: Minimum Serum Concentration (Cmin) of Atezolizumab

Primary: Minimum Serum Concentration (Cmin) of Atezolizumab

Primary: Atezolizumab Serum Concentration at Washout

Primary: Atezolizumab Serum Concentration at Washout

Primary: Area Under the Concentration-Time Curve (AUC) of Atezolizumab

Primary: Area Under the Concentration-Time Curve (AUC) of Atezolizumab

Primary: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab

Primary: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab

Secondary: Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 Criteria in Participants With Solid Tumors

Secondary: Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 Criteria in Participants With Solid Tumors

Secondary: DOR as Determined by the Investigator Using mINRC in Participants With Neuroblastoma

Secondary: DOR as Determined by the Investigator Using mINRC in Participants With Neuroblastoma

Secondary: DOR as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Secondary: DOR as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Secondary: DOR as Determined by the Investigator Using RANO Criteria in Participants With ATRT

Secondary: DOR as Determined by the Investigator Using RANO Criteria in Participants With ATRT

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors

Secondary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors

Secondary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Related Response Criteria (irRC) for Participants With Neuroblastoma

Secondary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Related Response Criteria (irRC) for Participants With Neuroblastoma

Secondary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using irRC for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Secondary: Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using irRC for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Secondary: PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors

Secondary: PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors

Secondary: PFS as Determined by the Investigator Using irRC for Participants With Neuroblastoma

Secondary: PFS as Determined by the Investigator Using irRC for Participants With Neuroblastoma

Secondary: PFS as Determined by the Investigator Using irRC for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Secondary: PFS as Determined by the Investigator Using irRC for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Secondary: DOR as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors

Secondary: DOR as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors

Secondary: DOR as Determined by the Investigator Using irRC for Participants With Neuroblastoma

Secondary: DOR as Determined by the Investigator Using irRC for Participants With Neuroblastoma

Secondary: DOR as Determined by the Investigator Using irRC for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Secondary: DOR as Determined by the Investigator Using irRC for Participants With Hodgkin’s Lymphoma or Non-Hodgkin’s Lymphoma

Secondary: Optimal Dose of Atezolizumab in Pediatric and Young Adult Participants

Secondary: Optimal Dose of Atezolizumab in Pediatric and Young Adult Participants

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An Early-Phase, Multicenter, Open-Label Study of the Safety and Pharmacokinetics of Atezolizumab (MPDL3280A) In Pediatric and Young Adult Patients With Previously Treated Solid Tumors