A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of Atezolizumab (Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) in Pediatric and Young Adult Participants With Solid Tumors

• ClinicalTrials.gov Identifier: NCT02541604
• Recruitment Status: Terminated
• First Posted: September 4, 2015
• Results First Posted: February 25, 2020
• Last Update Posted: February 25, 2020
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor
• Intervention: Drug: Atezolizumab
• Enrollment: 87

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	COHORT 1	COHORT 2	COHORT 3	COHORT 4	COHORT 5	COHORT 6	COHORT 7	COHORT 8	COHORT 9	COHORT 10	COHORT 11	COHORT 12
Arm/Group Description	EWING SARCOMA	HODGKIN LYMPHOMA	NEUROBLASTOMA	NON HODGKIN LYMPHOMA	NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA;	OSTEOSARCOMA	RHABDOMYOSARCOMA	WILMS TUMOR	OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION	OTHER TUMOR TYPES WITHOUT DOCUMENTED PD-L1 EXPRESSION	RHABDOID TUMOR	ATYPICAL TERATOID RHABDOID TUMOR
Period Title: Overall Study
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
Reason Not Completed
Death	6	5	7	2	9	8	9	9	3	4	2	3
Lost to Follow-up	2	0	1	0	0	1	1	0	0	0	0	0
Withdrawal by Subject	2	0	1	0	1	1	0	0	1	0	0	0
Study Terminated by Sponsor	1	4	2	1	0	0	0	0	0	0	0	0
Medical condition may jeopardize safety	0	0	0	0	0	0	0	1	0	0	0	0

Baseline Characteristics

Arm/Group Title		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
Arm/Group Description		EWING SARCOMA	HODGKIN LYMPHOMA	NEUROBLASTOMA	NON HODGKIN LYMPHOMA	NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA;	OSTEOSARCOMA	RHABDOMYOSARCOMA	WILMS TUMOR	OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION	OTHER TUMOR TYPES WITHOUT DOCUMENTED PD-L1 EXPRESSION	RHABDOID TUMOR	ATYPICAL TERATOID RHABDOID TUMOR	Total of all reporting groups
Overall Number of Baseline Participants		11	9	11	3	10	10	10	10	4	4	2	3	87
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	11 participants	9 participants	11 participants	3 participants	10 participants	10 participants	10 participants	10 participants	4 participants	4 participants	2 participants	3 participants	87 participants
		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)	13.5 (6.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants	9 participants	11 participants	3 participants	10 participants	10 participants	10 participants	10 participants	4 participants	4 participants	2 participants	3 participants	87 participants
	Female	5 45.5%	6 66.7%	4 36.4%	0 0.0%	5 50.0%	4 40.0%	4 40.0%	6 60.0%	0 0.0%	4 100.0%	1 50.0%	1 33.3%	40 46.0%
	Male	6 54.5%	3 33.3%	7 63.6%	3 100.0%	5 50.0%	6 60.0%	6 60.0%	4 40.0%	4 100.0%	0 0.0%	1 50.0%	2 66.7%	47 54.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants	9 participants	11 participants	3 participants	10 participants	10 participants	10 participants	10 participants	4 participants	4 participants	2 participants	3 participants	87 participants
	Hispanic or Latino	2 18.2%	1 11.1%	2 18.2%	1 33.3%	1 10.0%	2 20.0%	3 30.0%	1 10.0%	2 50.0%	0 0.0%	0 0.0%	1 33.3%	16 18.4%
	Not Hispanic or Latino	7 63.6%	5 55.6%	7 63.6%	2 66.7%	5 50.0%	6 60.0%	6 60.0%	6 60.0%	2 50.0%	3 75.0%	2 100.0%	0 0.0%	51 58.6%
	Unknown or Not Reported	2 18.2%	3 33.3%	2 18.2%	0 0.0%	4 40.0%	2 20.0%	1 10.0%	3 30.0%	0 0.0%	1 25.0%	0 0.0%	2 66.7%	20 23.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants	9 participants	11 participants	3 participants	10 participants	10 participants	10 participants	10 participants	4 participants	4 participants	2 participants	3 participants	87 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 10.0%	0 0.0%	0 0.0%	1 25.0%	0 0.0%	0 0.0%	1 33.3%	3 3.4%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	1 9.1%	1 33.3%	0 0.0%	1 10.0%	0 0.0%	1 10.0%	1 25.0%	1 25.0%	0 0.0%	0 0.0%	6 6.9%
	White	8 72.7%	5 55.6%	5 45.5%	2 66.7%	6 60.0%	6 60.0%	8 80.0%	5 50.0%	1 25.0%	2 50.0%	2 100.0%	0 0.0%	50 57.5%
	More than one race	1 9.1%	0 0.0%	1 9.1%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 2.3%
	Unknown or Not Reported	2 18.2%	4 44.4%	4 36.4%	0 0.0%	4 40.0%	2 20.0%	2 20.0%	4 40.0%	1 25.0%	1 25.0%	0 0.0%	2 66.7%	26 29.9%

Outcome Measures

1. Primary Outcome

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
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.
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 1	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10	Cohort 11
Arm/Group Description:	Participants with ewing sarcoma	Participants with non-rhabdomyosarcoma soft tissue sarcoma	Participants with osteosarcoma.	Participants with rhabdomyosarcoma	Participants with wilms tumor	Participants with other tumor types with documented PD-L1 expression.	Participants with other tumor types without documented PD-L1 expression.	Participants with rhabdoid tumor.
Overall Number of Participants Analyzed	11	10	10	10	10	4	4	2
Measure Type: Number; Unit of Measure: Percentage
	0	10.0	0	0	0	0	0	0

2. Primary Outcome

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
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 3
Arm/Group Description:	Participants with neuroblastoma.
Overall Number of Participants Analyzed	11
Measure Type: Number; Unit of Measure: Percentage
	0

3. Primary Outcome

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
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 2	Cohort 4
Arm/Group Description:	Participants with Hodgkin's lymphoma	Participants with non-Hodgkin's lymphoma
Overall Number of Participants Analyzed	9	3
Measure Type: Number; Unit of Measure: Percentage
	22.2	33.3

4. Primary Outcome

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)
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 12
Arm/Group Description:	Participants with atypical teratoid rhabdoid tumor.
Overall Number of Participants Analyzed	3
Measure Type: Number; Unit of Measure: Percentage
	0

5. Primary Outcome

Title	Percentage of Participants With Clinical Benefit as Determined by the Investigator According to RECIST v1.1 Criteria in Participants With Osteosarcoma
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population (defined as patients who received any amount of study drug), in the Osteosarcoma cohort as per protocol. (Objective response for the other cohorts are measured with different response criteria, and these are described in Outcome Measures 1, 2, 3, and 4).

Arm/Group Title	Cohort 6
Arm/Group Description:	Participants with osteosarcoma.
Overall Number of Participants Analyzed	10
Measure Type: Number; Unit of Measure: Percentage
	0

6. Primary Outcome

Title	Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors
Description	[Not Specified]
Time Frame	Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 1	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10	Cohort 11
Arm/Group Description:	Participants with ewing sarcoma.	Participants with non-rhabdomyosarcoma soft tissue sarcoma	Participants with osteosarcoma.	Participants with rhabdomyosarcoma.	Participants with wilms tumor.	Participants with other tumor types with documented PD-L1 expression.	Participant with other tumor types without documented PD-L1 expression.	Participants with rhabdoid tumor.
Overall Number of Participants Analyzed	11	10	10	10	10	4	4	2
Median (95% Confidence Interval); Unit of Measure: Months
	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)

7. Primary Outcome

Title	PFS as Determined by the Investigator Using mINRC in Participants With Neuroblastoma
Description	[Not Specified]
Time Frame	Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 3
Arm/Group Description:	Participants with neuroblastoma.
Overall Number of Participants Analyzed	11
Median (95% Confidence Interval); Unit of Measure: Months
	2.6; (1.2 to 4.7)

8. Primary Outcome

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
Description	[Not Specified]
Time Frame	Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 2	Cohort 4
Arm/Group Description:	Participants with hodgkin's lymphoma.	Participants with non-hodgkin's lymphoma.
Overall Number of Participants Analyzed	9	3
Median (95% Confidence Interval); Unit of Measure: Months
	2.8; (2.6 to 4.4)	1.4 [1]; (1.1 to NA)

[1]

More than 50% patient was censored.

9. Primary Outcome

Title	PFS as Determined by the Investigator Using RANO Criteria in Participants With ATRT
Description	[Not Specified]
Time Frame	Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 12
Arm/Group Description:	Participants with atypical teratoid rhabdoid tumor.
Overall Number of Participants Analyzed	3
Median (95% Confidence Interval); Unit of Measure: Months
	1.4; (1.4 to 1.7)

10. Primary Outcome

Title	Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest
Description	[Not Specified]
Time Frame	From baseline up to approximately 42 months

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Atezolizumab
Arm/Group Description:	Participants received intravenous (IV) infusion of atezolizumab (maximum 1200 milligrams [mg]) on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed	87
Measure Type: Number; Unit of Measure: Percentage
Adverse Events	97.7
Serious Adverse Events	37.9
Adverse Events of Special Interest	44.8

11. Primary Outcome

Title	Maximum Serum Concentration (Cmax) of Atezolizumab
Description	[Not Specified]
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Included PK population, defined as patients who had received any amount of study drug and had at least one serum concentration result available at clinical data cutoff. In the "<2 Age (Years)" Arm/Group, 1 participant died after study entry with 1 cycle, and the other participant died after two cycles.

Arm/Group Title		<2 Age (Years)	2 to <12 Age (Years)	12 to <18 Age (Years)	>=18 Age (Years)
Arm/Group Description:		Participants <2 Age (Years)	Participants 2 to <12 Age (Years)	Participants 12 to <18 Age (Years)	Participants >=18 Age (Years)
Overall Number of Participants Analyzed		2	26	34	18
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ug/mL
Cycle 1	Number Analyzed	2 participants	26 participants	34 participants	18 participants
		105; (6.90%)	312; (28.7%)	337; (26.8%)	424; (26.9%)
Cycle 4	Number Analyzed	0 participants	11 participants	16 participants	6 participants
			382; (16.4%)	373; (78.9%)	626; (29.2%)

12. Primary Outcome

Title	Minimum Serum Concentration (Cmin) of Atezolizumab
Description	[Not Specified]
Time Frame	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 42 months)

Outcome Measure Data

Analysis Population Description

Included PK population, defined as patients who had received any amount of study drug and had at least one serum concentration result available at clinical data cutoff. In the "<2 Age (Years)" Arm/Group, 1 participant died after study entry with 1 cycle, and the other participant died after two cycles.

Arm/Group Title		<2 Age (Years)	2 to <12 Age (Years)	12 to <18 Age (Years)	>=18 Age (Years)
Arm/Group Description:		Participants <2 Age (Years)	Participants 2 to <12 Age (Years)	Participants 12 to <18 Age (Years)	Participants >=18 Age (Years)
Overall Number of Participants Analyzed		1	25	32	16
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ug/mL
Cycle 2	Number Analyzed	1 participants	25 participants	32 participants	16 participants
		24.1 [1]; (NA%)	59.3; (31.4%)	56.5; (50.4%)	79.9; (52.7%)
Cycle 3	Number Analyzed	0 participants	13 participants	19 participants	8 participants
			58.9; (234.4%)	85.0; (47.4%)	148; (48.9%)
Cycle 4	Number Analyzed	0 participants	11 participants	16 participants	6 participants
			99.2; (36.4%)	113; (41.1%)	121; (80.4%)
Cycle 8	Number Analyzed	0 participants	4 participants	4 participants	2 participants
			166; (19.8%)	145; (21.9%)	209; (8.10%)

[1]

Later cycles are NA because 1 participant died after study entry with 1 cycle, and the other participant died after two cycles.

13. Primary Outcome

Title	Atezolizumab Serum Concentration at Washout
Description	[Not Specified]
Time Frame	At least 90 days (maximum 150 days) after last dose of study drug (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included PK population, defined as patients who had received any amount of study drug and had at least one serum concentration result available at clinical data cutoff.

Arm/Group Title	Atezolizumab
Arm/Group Description:	Participants received intravenous (IV) infusion of atezolizumab (maximum 1200 milligrams [mg]) on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed	17
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ug/mL
	1.91; (2815.1%)

14. Primary Outcome

Title	Area Under the Concentration-Time Curve (AUC) of Atezolizumab
Description	[Not Specified]
Time Frame	PRD (0 hr), 0.5 hr P-I (infusion duration=30-60 minutes) on D1 of Cy1; at any time during visit on Cy1D8 (1 Cy=21 days)

Outcome Measure Data

Analysis Population Description

Included PK population, defined as patients who had received any amount of study drug and had at least one serum concentration result available at clinical data cutoff.

Arm/Group Title	<2 Age (Years)	2 to <12 Age (Years)	12 to <18 Age (Years)	>=18 Age (Years)
Arm/Group Description:	Participants <2 Age (Years)	Participants 2 to <12 Age (Years)	Participants 12 to <18 Age (Years)	Participants >=18 Age (Years)
Overall Number of Participants Analyzed	2	29	38	18
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ugxday/mL
	1130; (5.28%)	2209; (21.3%)	2816; (17.7%)	3579; (28.4%)

15. Primary Outcome

Title	Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Description	[Not Specified]
Time Frame	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 42 months)

Outcome Measure Data

Analysis Population Description

The baseline ADA-evaluable population included patients who had a baseline ADA result. The post-baseline ADA-evaluable population included patients who had at least one post-baseline ADA result and had received at least one dose of that study treatment. Patients never dosed and patients without valid ADA records were not included in the analysis.

Arm/Group Title		Atezolizumab
Arm/Group Description:		Participants received intravenous (IV) infusion of atezolizumab (maximum 1200 milligrams [mg]) on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed		78
Measure Type: Number; Unit of Measure: Percentage
Baseline	Number Analyzed	78 participants
		2.6
Post-baseline	Number Analyzed	77 participants
		14.3

16. Secondary Outcome

Title	Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 Criteria in Participants With Solid Tumors
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 1	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10	Cohort 11
Arm/Group Description:	Participants with ewing sarcoma	Participants with non-rhabdomyosarcoma soft tissue sarcoma.	Participants with osteosarcoma.	Participants with rhabdomyosarcoma	Participants with wilms tumor.	Participants with other tumor types with documented PD-L1 expression.	Participants with other tumor types without documented PD-L1 expression.	Participants with rhabdoid tumor.
Overall Number of Participants Analyzed	0	1	0	0	0	0	0	0
Median (95% Confidence Interval); Unit of Measure: Months
		13.2 [1]; (NA to NA)

[1]

There was only 1 participant.

17. Secondary Outcome

Title	DOR as Determined by the Investigator Using mINRC in Participants With Neuroblastoma
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 3
Arm/Group Description:	Participants with neuroblastoma.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

18. Secondary Outcome

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
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 2	Cohort 4
Arm/Group Description:	Participants with hodgkin lymphoma.	Participants with non-hodgkin's lymphoma
Overall Number of Participants Analyzed	2	1
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (4.1 to NA)	NA [1]; (NA to NA)

[1]

Kaplan-Meier median estimate not reached.

19. Secondary Outcome

Title	DOR as Determined by the Investigator Using RANO Criteria in Participants With ATRT
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug. No participants had an objective response in this cohort.

Arm/Group Title	Cohort 12
Arm/Group Description:	Participants with atypical teratoid rhabdoid tumor.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

20. Secondary Outcome

Title	Overall Survival (OS)
Description	[Not Specified]
Time Frame	Baseline until death (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Atezolizumab
Arm/Group Description:	Participants received intravenous (IV) infusion of atezolizumab (maximum 1200 milligrams [mg]) on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed	87
Median (95% Confidence Interval); Unit of Measure: Months
	7.4; (5.3 to 9.6)

21. Secondary Outcome

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
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 1	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10	Cohort 11	Cohort 12
Arm/Group Description:	Participants with ewing sarcoma.	Participants with non-rhabdomyosarcoma.	Participants with osteosarcoma.	Participants with rhabdomyosarcoma.	Participants with wilms tumor.	Participants with other tumor types with documented PD-L1 expression.	Participants with other tumor types without documented PD-L1 expression.	Participants with rhabdoid tumor.	Participants with atypical teratoid rhabdoid tumor.
Overall Number of Participants Analyzed	11	10	10	10	10	4	4	2	3
Measure Type: Number; Unit of Measure: Percentage
	0	10	0	0	0	0	0	0	0

22. Secondary Outcome

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
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 3
Arm/Group Description:	Participants with neuroblastoma.
Overall Number of Participants Analyzed	11
Measure Type: Number; Unit of Measure: Percentage
	0

23. Secondary Outcome

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
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 2	Cohort 4
Arm/Group Description:	Participants with hodgkin's lymphoma.	Participants with non-hodgkin lymphoma.
Overall Number of Participants Analyzed	9	3
Measure Type: Number; Unit of Measure: Percentage
	33.3	33.3

24. Secondary Outcome

Title	PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 1	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10	Cohort 11	Cohort 12
Arm/Group Description:	Participants with ewing sarcoma.	Participants with non-rhabdomyosarcoma soft tissue sarcoma.	Participants with osteosarcoma.	Participants with rhabdomyosarcoma.	Participants with wilms tumor.	Participants with other tumor types with documented PD-L1 expression.	Participants with other tumor types without documented PD-L1 expression.	Participants with rhabdoid tumor.	Participants with atypical teratoid rhabdoid tumor.
Overall Number of Participants Analyzed	11	10	10	10	10	4	4	2	3
Median (95% Confidence Interval); Unit of Measure: Months
	1.3; (0.6 to 1.4)	1.4; (1.3 to 3.7)	1.2; (0.9 to 1.8)	1.3; (1.1 to 1.8)	1.4; (1.1 to 2.8)	1.2; (0.7 to 1.3)	1.2; (1.1 to 10.1)	0.7; (0.3 to 1.1)	6.9; (1.7 to 9.3)

25. Secondary Outcome

Title	PFS as Determined by the Investigator Using irRC for Participants With Neuroblastoma
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 3
Arm/Group Description:	Participants with neuroblastoma
Overall Number of Participants Analyzed	11
Median (95% Confidence Interval); Unit of Measure: Months
	6.9; (2.6 to 14.7)

26. Secondary Outcome

Title	PFS as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 2	Cohort 4
Arm/Group Description:	Participants with hodgkin lymphoma	Participants with non-hodgkin's lymphoma
Overall Number of Participants Analyzed	9	3
Median (95% Confidence Interval); Unit of Measure: Months
	6.5 [1]; (2.6 to NA)	3.7 [1]; (1.4 to NA)

[1]

More than 50% patient was censored.

27. Secondary Outcome

Title	DOR as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 1	Cohort 5	Cohort 6	Cohort 7	Cohort 8	Cohort 9	Cohort 10	Cohort 11	Cohort 12
Arm/Group Description:	Participants with ewing sarcoma.	Participants with non-rhabdomyosarcoma soft tissue sarcoma.	Participants with osteosarcoma.	Participants with rhabdomyosarcoma.	Participants with wilms tumor.	Participants with other tumor types with documented PD-L1 expression.	Participants with other tumor types without documented PD-L1 expression.	Participants with rhabdoid tumor.	Participants with atypical teratoid rhabdoid tumor.
Overall Number of Participants Analyzed	0	1	0	0	0	0	0	0	0
Median (95% Confidence Interval); Unit of Measure: Months
		13.2 [1]; (NA to NA)

[1]

There was only 1 participant with response.

28. Secondary Outcome

Title	DOR as Determined by the Investigator Using irRC for Participants With Neuroblastoma
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug. No participants had response therefore no participants analyzed.

Arm/Group Title	Cohort 3
Arm/Group Description:	Participants with neuroblastoma
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

29. Secondary Outcome

Title	DOR as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
Description	[Not Specified]
Time Frame	Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Included safety-evaluable population, defined as patients who received any amount of study drug.

Arm/Group Title	Cohort 2	Cohort 4
Arm/Group Description:	Participants with Hodgkin lymphoma.	Participants with non-hodgkin's lymphoma
Overall Number of Participants Analyzed	3	1
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (7.3 to NA)	NA [1]; (NA to NA)

[1]

Kaplan-Meier median estimate not reached.

30. Secondary Outcome

Title	Optimal Dose of Atezolizumab in Pediatric Adult Participants
Description	Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.
Time Frame	From baseline up to approximately 42 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	<18 Age (Years)
Arm/Group Description:	Participants <18 Age (Years)
Overall Number of Participants Analyzed	69
Measure Type: Number; Unit of Measure: mg/kg
	15

31. Secondary Outcome

Title	Optimal Dose of Atezolizumab in Young Adult Participants
Description	Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.
Time Frame	From baseline up to approximately 42 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	>=18 Age (Years)
Arm/Group Description:	Participants >=18 Age (Years)
Overall Number of Participants Analyzed	18
Measure Type: Number; Unit of Measure: mg
	1200

Adverse Events

Time Frame	From baseline up to approximately 42 months
Adverse Event Reporting Description	Adverse Events reporting is for the Safety Evaluable Population, defined as patients who received any amount of any component of study treatment.
Arm/Group Title	COHORT 1		COHORT 2		COHORT 3		COHORT 4		COHORT 5		COHORT 6		COHORT 7		COHORT 8		COHORT 9		COHORT 10		COHORT 11		COHORT 12
Arm/Group Description	EWING SARCOMA		HODGKIN LYMPHOMA		NEUROBLASTOMA		NON HODGKIN LYMPHOMA		NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMA;		OSTEOSARCOMA		RHABDOMYOSARCOMA		WILMS TUMOR		OTHER TUMOR TYPES WITH DOCUMENTED PD-L1 EXPRESSION		OTHER TUMOR TYPES WITHOUT DOCUMENTED PD-L1 EXPRESSION		RHABDOID TUMOR		ATYPICAL TERATOID RHABDOID TUMOR
All-Cause Mortality
	COHORT 1		COHORT 2		COHORT 3		COHORT 4		COHORT 5		COHORT 6		COHORT 7		COHORT 8		COHORT 9		COHORT 10		COHORT 11		COHORT 12
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	6/11 (54.55%)		5/9 (55.56%)		7/11 (63.64%)		2/3 (66.67%)		9/10 (90.00%)		8/10 (80.00%)		9/10 (90.00%)		9/10 (90.00%)		3/4 (75.00%)		4/4 (100.00%)		2/2 (100.00%)		3/3 (100.00%)
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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	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%)
Blood and lymphatic system disorders
ANAEMIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
FEBRILE NEUTROPENIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Eye disorders
PAPILLOEDEMA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
Gastrointestinal disorders
ABDOMINAL DISTENSION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
CONSTIPATION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
LARGE INTESTINAL OBSTRUCTION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PANCREATITIS † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
UPPER GASTROINTESTINAL HAEMORRHAGE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
General disorders
CHEST PAIN † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	2/10 (20.00%)	2	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
FATIGUE † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PAIN † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PYREXIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	2/10 (20.00%)	3	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Hepatobiliary disorders
CHOLESTASIS † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Immune system disorders
GRAFT VERSUS HOST DISEASE † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Infections and infestations
ABDOMINAL ABSCESS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DEVICE RELATED INFECTION † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
INCISION SITE ABSCESS † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
LUNG INFECTION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/2 (50.00%)	1	0/3 (0.00%)	0
POSTOPERATIVE ABSCESS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PYELONEPHRITIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
RESPIRATORY TRACT INFECTION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
SEPTIC SHOCK † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
STAPHYLOCOCCAL SEPSIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	2	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
URINARY TRACT INFECTION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Injury, poisoning and procedural complications
POSTOPERATIVE HYPOTENSION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
TOXICITY TO VARIOUS AGENTS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Metabolism and nutrition disorders
DEHYDRATION † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DIABETIC KETOACIDOSIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPONATRAEMIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Musculoskeletal and connective tissue disorders
BONE PAIN † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
FLANK PAIN † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Nervous system disorders
HEADACHE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
HYDROCEPHALUS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	1/3 (33.33%)	1
PARAESTHESIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
VITH NERVE DISORDER † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
Psychiatric disorders
AGITATION † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Renal and urinary disorders
HYDRONEPHROSIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
URINARY TRACT OBSTRUCTION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
DYSPNOEA † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PLEURAL EFFUSION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	1/4 (25.00%)	4	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PNEUMOTHORAX † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
Skin and subcutaneous tissue disorders
PRURITUS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
RASH MACULO-PAPULAR † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
TOXIC SKIN ERUPTION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Vascular disorders
SHOCK HAEMORRHAGIC † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
SUPERIOR VENA CAVA SYNDROME † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
1 Term from vocabulary, MedDRA version 22.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	COHORT 1		COHORT 2		COHORT 3		COHORT 4		COHORT 5		COHORT 6		COHORT 7		COHORT 8		COHORT 9		COHORT 10		COHORT 11		COHORT 12
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	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%)
Blood and lymphatic system disorders
ANAEMIA † 1	3/11 (27.27%)	4	1/9 (11.11%)	1	3/11 (27.27%)	6	1/3 (33.33%)	1	5/10 (50.00%)	12	2/10 (20.00%)	2	3/10 (30.00%)	3	2/10 (20.00%)	2	1/4 (25.00%)	1	1/4 (25.00%)	1	1/2 (50.00%)	1	1/3 (33.33%)	1
FEBRILE NEUTROPENIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	2/10 (20.00%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
LEUKOPENIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
LYMPHADENOPATHY † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	2	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
LYMPHOPENIA † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	2	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
NEUTROPENIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
THROMBOCYTOPENIA † 1	2/11 (18.18%)	3	2/9 (22.22%)	2	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	2/10 (20.00%)	2	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
THROMBOCYTOSIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Cardiac disorders
PERICARDIAL EFFUSION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
SINUS TACHYCARDIA † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	2/10 (20.00%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
TACHYCARDIA † 1	1/11 (9.09%)	1	1/9 (11.11%)	1	0/11 (0.00%)	0	1/3 (33.33%)	1	1/10 (10.00%)	1	1/10 (10.00%)	1	2/10 (20.00%)	2	1/10 (10.00%)	1	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Congenital, familial and genetic disorders
FANCONI SYNDROME † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
Ear and labyrinth disorders
EAR PAIN † 1	1/11 (9.09%)	1	2/9 (22.22%)	3	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
VERTIGO † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Endocrine disorders
HYPERTHYROIDISM † 1	0/11 (0.00%)	0	2/9 (22.22%)	3	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPOTHYROIDISM † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	1/3 (33.33%)	1
Eye disorders
ECZEMA EYELIDS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
EYELID PTOSIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
OPSOCLONUS MYOCLONUS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PERIORBITAL OEDEMA † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PHOTOPHOBIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	3	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PHOTOPSIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
VISION BLURRED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	1/3 (33.33%)	1
Gastrointestinal disorders
ABDOMINAL PAIN † 1	3/11 (27.27%)	3	2/9 (22.22%)	2	2/11 (18.18%)	2	0/3 (0.00%)	0	2/10 (20.00%)	4	3/10 (30.00%)	3	1/10 (10.00%)	1	3/10 (30.00%)	5	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	1/3 (33.33%)	1
ABDOMINAL PAIN LOWER † 1	0/11 (0.00%)	0	1/9 (11.11%)	2	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ABDOMINAL PAIN UPPER † 1	1/11 (9.09%)	1	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ANAL INCONTINENCE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ASCITES † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
COLITIS † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
CONSTIPATION † 1	3/11 (27.27%)	6	1/9 (11.11%)	1	2/11 (18.18%)	2	1/3 (33.33%)	1	6/10 (60.00%)	6	6/10 (60.00%)	7	2/10 (20.00%)	2	6/10 (60.00%)	7	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DENTAL CARIES † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DIARRHOEA † 1	0/11 (0.00%)	0	2/9 (22.22%)	3	4/11 (36.36%)	5	0/3 (0.00%)	0	4/10 (40.00%)	6	4/10 (40.00%)	5	2/10 (20.00%)	3	2/10 (20.00%)	2	1/4 (25.00%)	1	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
DYSPEPSIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DYSPHAGIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ENTEROCOLITIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HAEMATOCHEZIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
LIP ULCERATION † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
NAUSEA † 1	4/11 (36.36%)	4	1/9 (11.11%)	3	1/11 (9.09%)	2	0/3 (0.00%)	0	2/10 (20.00%)	2	4/10 (40.00%)	7	0/10 (0.00%)	0	2/10 (20.00%)	2	1/4 (25.00%)	2	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
NONINFECTIVE GINGIVITIS † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ODYNOPHAGIA † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ORAL PAIN † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PROCTALGIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	2	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
RECTAL DISCHARGE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
STOMATITIS † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
SUBILEUS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
SWOLLEN TONGUE † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
UPPER GASTROINTESTINAL HAEMORRHAGE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
VOMITING † 1	3/11 (27.27%)	4	3/9 (33.33%)	6	2/11 (18.18%)	2	0/3 (0.00%)	0	3/10 (30.00%)	5	3/10 (30.00%)	4	1/10 (10.00%)	2	4/10 (40.00%)	5	1/4 (25.00%)	2	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
General disorders
ASTHENIA † 1	1/11 (9.09%)	1	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	2	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
AXILLARY PAIN † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
CATHETER SITE ERYTHEMA † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
CHEST DISCOMFORT † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
CHEST PAIN † 1	1/11 (9.09%)	1	1/9 (11.11%)	1	1/11 (9.09%)	1	0/3 (0.00%)	0	1/10 (10.00%)	1	2/10 (20.00%)	5	0/10 (0.00%)	0	2/10 (20.00%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
CHILLS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
FACE OEDEMA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
FATIGUE † 1	2/11 (18.18%)	3	2/9 (22.22%)	2	3/11 (27.27%)	3	0/3 (0.00%)	0	4/10 (40.00%)	13	6/10 (60.00%)	6	3/10 (30.00%)	3	6/10 (60.00%)	7	1/4 (25.00%)	1	2/4 (50.00%)	2	0/2 (0.00%)	0	1/3 (33.33%)	1
GENERALISED OEDEMA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
INFLUENZA LIKE ILLNESS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	2	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	2	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
MALAISE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
NON-CARDIAC CHEST PAIN † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
OEDEMA † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
OEDEMA PERIPHERAL † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
PAIN † 1	2/11 (18.18%)	2	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	2	0/10 (0.00%)	0	0/10 (0.00%)	0	2/10 (20.00%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PERIPHERAL SWELLING † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
PYREXIA † 1	3/11 (27.27%)	5	3/9 (33.33%)	9	4/11 (36.36%)	5	2/3 (66.67%)	2	2/10 (20.00%)	5	8/10 (80.00%)	14	5/10 (50.00%)	6	4/10 (40.00%)	5	1/4 (25.00%)	2	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
THIRST † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
VACCINATION SITE OEDEMA † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Hepatobiliary disorders
HYPERBILIRUBINAEMIA † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	1/3 (33.33%)	1	1/10 (10.00%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Infections and infestations
BACTERAEMIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
BRONCHITIS † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
CANDIDA URETHRITIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
CONJUNCTIVITIS † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DERMATOPHYTOSIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DEVICE RELATED INFECTION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
FUNGAL SKIN INFECTION † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
GENITAL HERPES † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HERPES VIRUS INFECTION † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
INFLUENZA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	2/10 (20.00%)	3	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
LARYNGITIS † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
LUNG INFECTION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
NASOPHARYNGITIS † 1	1/11 (9.09%)	1	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ORAL CANDIDIASIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
ORAL HERPES † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PARONYCHIA † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PHARYNGITIS † 1	0/11 (0.00%)	0	2/9 (22.22%)	2	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	2/10 (20.00%)	2	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
PYELONEPHRITIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
RHINITIS † 1	0/11 (0.00%)	0	4/9 (44.44%)	16	2/11 (18.18%)	2	1/3 (33.33%)	1	1/10 (10.00%)	1	1/10 (10.00%)	2	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
SKIN INFECTION † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
STAPHYLOCOCCAL † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
TONSILLITIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
UPPER RESPIRATORY TRACT INFECTION † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
URINARY TRACT INFECTION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
VASCULAR DEVICE INFECTION † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
VULVITIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Injury, poisoning and procedural complications
ARTHROPOD BITE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
FALL † 1	1/11 (9.09%)	1	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	2	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
LIMB INJURY † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
POST PROCEDURAL SWELLING † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PROCEDURAL PAIN † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
THERMAL BURN † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	2	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
UROSTOMY COMPLICATION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
WOUND DEHISCENCE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
CONTUSION † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED † 1	1/11 (9.09%)	1	1/9 (11.11%)	3	3/11 (27.27%)	3	0/3 (0.00%)	0	1/10 (10.00%)	1	2/10 (20.00%)	3	0/10 (0.00%)	0	1/10 (10.00%)	1	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
AMYLASE INCREASED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	2/10 (20.00%)	2	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ANTITHROMBIN III DECREASED † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ASPARTATE AMINOTRANSFERASE INCREASED † 1	0/11 (0.00%)	0	1/9 (11.11%)	3	4/11 (36.36%)	4	0/3 (0.00%)	0	0/10 (0.00%)	0	2/10 (20.00%)	2	0/10 (0.00%)	0	2/10 (20.00%)	4	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
BLOOD ALKALINE PHOSPHATASE INCREASED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
BLOOD BILIRUBIN INCREASED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
BLOOD CHLORIDE DECREASED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
BLOOD CREATININE INCREASED † 1	2/11 (18.18%)	2	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	3/10 (30.00%)	3	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
BLOOD LACTATE DEHYDROGENASE INCREASED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
BLOOD POTASSIUM DECREASED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
BLOOD THYROID STIMULATING HORMONE INCREASED † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	2/10 (20.00%)	2	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
BLOOD URINE PRESENT † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
C-REACTIVE PROTEIN INCREASED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
CANDIDA TEST POSITIVE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
CARDIAC MURMUR † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
GAMMA-GLUTAMYLTRANSFERASE INCREASED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
INTERNATIONAL NORMALISED RATIO INCREASED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
LIPASE INCREASED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
LYMPHOCYTE COUNT DECREASED † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	2/10 (20.00%)	4	3/10 (30.00%)	6	0/10 (0.00%)	0	2/10 (20.00%)	5	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
NEUTROPHIL COUNT DECREASED † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	2/10 (20.00%)	4	1/10 (10.00%)	3	0/10 (0.00%)	0	2/10 (20.00%)	5	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	1/3 (33.33%)	1
NOROVIRUS TEST POSITIVE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
OXYGEN SATURATION DECREASED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PLATELET COUNT DECREASED † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	2/10 (20.00%)	3	2/10 (20.00%)	3	0/10 (0.00%)	0	2/10 (20.00%)	4	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PROTHROMBIN LEVEL DECREASED † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
VITAMIN K DECREASED † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
WEIGHT DECREASED † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	1/3 (33.33%)	1	2/10 (20.00%)	2	1/10 (10.00%)	1	1/10 (10.00%)	1	2/10 (20.00%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
WHITE BLOOD CELL COUNT DECREASED † 1	1/11 (9.09%)	2	0/9 (0.00%)	0	2/11 (18.18%)	2	0/3 (0.00%)	0	2/10 (20.00%)	3	2/10 (20.00%)	4	0/10 (0.00%)	0	1/10 (10.00%)	4	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	1/3 (33.33%)	1
Metabolism and nutrition disorders
DECREASED APPETITE † 1	4/11 (36.36%)	4	1/9 (11.11%)	1	2/11 (18.18%)	2	0/3 (0.00%)	0	2/10 (20.00%)	4	2/10 (20.00%)	2	1/10 (10.00%)	1	4/10 (40.00%)	5	1/4 (25.00%)	1	0/4 (0.00%)	0	1/2 (50.00%)	1	0/3 (0.00%)	0
DEHYDRATION † 1	2/11 (18.18%)	2	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPERGLYCAEMIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPERKALAEMIA † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPERNATRAEMIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPERTRIGLYCERIDAEMIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPERURICAEMIA † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPOALBUMINAEMIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPOCALCAEMIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPOKALAEMIA † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	1/10 (10.00%)	1	2/10 (20.00%)	3	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	2/4 (50.00%)	2	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPOMAGNESAEMIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	4	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPONATRAEMIA † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	3/10 (30.00%)	3	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPOPHOSPHATAEMIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	2	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
METABOLIC ACIDOSIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPERMAGNESAEMIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	3	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	4	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	1/11 (9.09%)	1	1/9 (11.11%)	1	2/11 (18.18%)	2	0/3 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	1/10 (10.00%)	1	1/10 (10.00%)	1	0/4 (0.00%)	0	1/4 (25.00%)	2	0/2 (0.00%)	0	0/3 (0.00%)	0
BACK PAIN † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	2/11 (18.18%)	3	0/3 (0.00%)	0	2/10 (20.00%)	2	1/10 (10.00%)	4	1/10 (10.00%)	1	2/10 (20.00%)	2	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	1/3 (33.33%)	2
FLANK PAIN † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HAEMARTHROSIS † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
MUSCLE SPASMS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
MUSCULOSKELETAL PAIN † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	2/10 (20.00%)	2	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
MYALGIA † 1	1/11 (9.09%)	1	1/9 (11.11%)	1	1/11 (9.09%)	1	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
NECK PAIN † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	2/11 (18.18%)	2	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	2/4 (50.00%)	2	0/2 (0.00%)	0	0/3 (0.00%)	0
PAIN IN EXTREMITY † 1	2/11 (18.18%)	4	1/9 (11.11%)	2	2/11 (18.18%)	2	0/3 (0.00%)	0	1/10 (10.00%)	2	2/10 (20.00%)	3	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	2/4 (50.00%)	3	0/2 (0.00%)	0	0/3 (0.00%)	0
PAIN IN JAW † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	2	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
JOINT SWELLING † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR INFLAMMATION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
TUMOUR PAIN † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	2/10 (20.00%)	2	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Nervous system disorders
AMPUTATION STUMP PAIN † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DYSGEUSIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HEADACHE † 1	2/11 (18.18%)	2	1/9 (11.11%)	8	3/11 (27.27%)	3	1/3 (33.33%)	1	2/10 (20.00%)	3	2/10 (20.00%)	8	2/10 (20.00%)	2	3/10 (30.00%)	5	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	1/3 (33.33%)	2
HYPOAESTHESIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	2/10 (20.00%)	2	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
MIGRAINE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
MIGRAINE WITH AURA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
NEURALGIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	2	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PARAESTHESIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PHANTOM LIMB SYNDROME † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
SEIZURE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
SOMNOLENCE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
TREMOR † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DIZZINESS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	2/10 (20.00%)	3	0/10 (0.00%)	0	0/10 (0.00%)	0	2/4 (50.00%)	2	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PARAPARESIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Product Issues
DEVICE BREAKAGE † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Psychiatric disorders
AGITATION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ANXIETY † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
BRUXISM † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
CONFUSIONAL STATE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DELIRIUM † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DEPRESSION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
INSOMNIA † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	1/4 (25.00%)	1	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
IRRITABILITY † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	4	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
SLEEP DISORDER † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ABNORMAL BEHAVIOUR † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Renal and urinary disorders
ACUTE KIDNEY INJURY † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DYSURIA † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	2/10 (20.00%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
GLYCOSURIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HAEMATURIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYDRONEPHROSIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
NEPHROLITHIASIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
OLIGURIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PROTEINURIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	2/10 (20.00%)	2	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
URINARY INCONTINENCE † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
URINARY RETENTION † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Reproductive system and breast disorders
PELVIC PAIN † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
VAGINAL DISCHARGE † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
VAGINAL HAEMORRHAGE † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
CATARRH † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
COUGH † 1	3/11 (27.27%)	4	4/9 (44.44%)	14	2/11 (18.18%)	2	1/3 (33.33%)	1	1/10 (10.00%)	1	5/10 (50.00%)	8	0/10 (0.00%)	0	1/10 (10.00%)	1	2/4 (50.00%)	2	1/4 (25.00%)	1	1/2 (50.00%)	1	1/3 (33.33%)	1
DYSPHONIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0	0/3 (0.00%)	0
DYSPNOEA † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	2/10 (20.00%)	2	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DYSPNOEA EXERTIONAL † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
EPISTAXIS † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPOXIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
IRREGULAR BREATHING † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
LARYNGEAL INFLAMMATION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
NASAL CONGESTION † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	2/11 (18.18%)	2	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	2	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DISORDER OROPHARYNGEAL PAIN † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PHARYNGEAL INFLAMMATION † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PLEURAL EFFUSION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PNEUMONITIS † 1	0/11 (0.00%)	0	2/9 (22.22%)	2	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
RHINITIS ALLERGIC † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
STRIDOR † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
TACHYPNOEA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ATELECTASIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
OBSTRUCTIVE AIRWAYS DISORDER † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
OROPHARYNGEAL PAIN † 1	0/11 (0.00%)	0	1/9 (11.11%)	2	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
RHINORRHOEA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Skin and subcutaneous tissue disorders
ALOPECIA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
BLISTER † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DERMATITIS † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DERMATITIS CONTACT † 1	0/11 (0.00%)	0	1/9 (11.11%)	2	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
DRY SKIN † 1	0/11 (0.00%)	0	1/9 (11.11%)	2	1/11 (9.09%)	1	1/3 (33.33%)	2	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ECZEMA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ERYTHEMA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPERHIDROSIS † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	2/10 (20.00%)	3	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PALMAR-PLANTAR † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
ERYTHRODYSAESTHESIA SYNDROME † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PERIORAL DERMATITIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PETECHIAE † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PITYRIASIS ROSEA † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
PRURITUS † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	1/3 (33.33%)	1	2/10 (20.00%)	2	1/10 (10.00%)	1	1/10 (10.00%)	1	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
RASH † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
RASH MACULO-PAPULAR † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
RASH PRURITIC † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
SKIN DISCOLOURATION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
URTICARIA † 1	1/11 (9.09%)	1	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Surgical and medical procedures
CENTRAL VENOUS CATHETERISATION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
Vascular disorders
EMBOLISM † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HOT FLUSH † 1	0/11 (0.00%)	0	1/9 (11.11%)	1	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPERTENSION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	1/10 (10.00%)	1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPOTENSION † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	1/11 (9.09%)	1	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
HYPOVOLAEMIC SHOCK † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
VENOUS THROMBOSIS † 1	0/11 (0.00%)	0	0/9 (0.00%)	0	0/11 (0.00%)	0	0/3 (0.00%)	0	1/10 (10.00%)	1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/10 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/2 (0.00%)	0	0/3 (0.00%)	0
1 Term from vocabulary, MedDRA version 22.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800-821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Geoerger B, Zwaan CM, Marshall LV, Michon J, Bourdeaut F, Casanova M, Corradini N, Rossato G, Farid-Kapadia M, Shemesh CS, Hutchinson KE, Donaldson F, Liao M, Caron H, Trippett T. Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Lancet Oncol. 2020 Jan;21(1):134-144. doi: 10.1016/S1470-2045(19)30693-X. Epub 2019 Nov 25.

Shemesh CS, Chanu P, Jamsen K, Wada R, Rossato G, Donaldson F, Garg A, Winter H, Ruppel J, Wang X, Bruno R, Jin J, Girish S. Population pharmacokinetics, exposure-safety, and immunogenicity of atezolizumab in pediatric and young adult patients with cancer. J Immunother Cancer. 2019 Nov 21;7(1):314. doi: 10.1186/s40425-019-0791-x.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02541604
• Other Study ID Numbers: GO29664; 2014-004697-41 ( EudraCT Number )
• First Submitted: August 18, 2015
• First Posted: September 4, 2015
• Results First Submitted: November 11, 2019
• Results First Posted: February 25, 2020
• Last Update Posted: February 25, 2020