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Clinical Trial Results:
A Phase 2b Randomized Study to Assess the Efficacy and Safety of the Combination of Ublituximab + Umbralisib With or Without Bendamustine and Umbralisib Alone in Patients With Previously Treated Non-Hodgkin’s Lymphoma

Summary
EudraCT number	2016-004718-90
Trial protocol	GB PL SK ES IT
Global end of trial date	04 Jul 2022

Results information
Results version number	v1(current)
This version publication date	19 Jul 2023
First version publication date	19 Jul 2023
Other versions

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

UTX-TGR-205

ISRCTN number

-

US NCT number

NCT02793583

WHO universal trial number (UTN)

-

Sponsor organisation name

TG Therapeutics, Inc

Sponsor organisation address

2 Gansevoort St., 9th Floor, New York, NY 10014, United States,

Public contact

Izabela Kozdraś-Urbanek, Brillance Sp. z o.o., +48 668166876, ikozdras@brillance.pl

Scientific contact

Izabela Kozdraś-Urbanek, Brillance Sp. z o.o., +48 668166876, ikozdras@brillance.pl

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

No

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

No

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

No

Analysis stage

Final

Date of interim/final analysis

04 Jul 2022

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

04 Jul 2022

Was the trial ended prematurely?

Yes

Main objective of the trial

Unity NHL - A Phase 2b randomised study to assess the efficacy and safety of the combination of ublituximab + umbralisib with or without bendamustine and umbralisib alone in subjects with previously treated non-hodgkin’s lymphoma. The purpose of this study was to evaluate the efficacy and safety of umbralisib monotherapy and the umbralisib + ublituximab (U2) combination in aggressive and indolent lymphomas and to also explore the U2 regimen in combination with bendamustine in the treatment of non-Hodgkin lymphomas (NHL) (follicular lymphoma (FL), small lymphocytic lymphoma (SLL), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL).

Protection of trial subjects

All study subjects were required to read and sign an informed consent form.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

25 May 2016

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Slovakia: 10

Country: Number of subjects enrolled

Spain: 15

Country: Number of subjects enrolled

United Kingdom: 45

Country: Number of subjects enrolled

Italy: 43

Country: Number of subjects enrolled

Australia: 29

Country: Number of subjects enrolled

Israel: 34

Country: Number of subjects enrolled

Poland: 94

Country: Number of subjects enrolled

United States: 449

Country: Number of subjects enrolled

Korea, Republic of: 16

Worldwide total number of subjects

735

EEA total number of subjects

162

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

277

From 65 to 84 years

418

85 years and over

40

Subject disposition

Top of page

Recruitment details

A total of 735 subjects took part in the study at 141 investigative sites in Australia, Israel, Italy, Poland, Slovakia, South Korea, Spain, the United Kingdom, and the United States from 25 May 2016 to 4 July 2022.

Screening details

After screening, a total of 735 subjects were enrolled in the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Arm A: Ublituximab + Umbralisib (TGR-1202)

Arm description

Subjects with FL, MZL, MCL, and DLBCL received ublituximab, 900 milligrams (mg), intravenous (IV), infusion on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6, and thereafter on Day 1 of every 3 cycles, through Cycle 24 (1 cycle=28 days) in combination with umbralisib, 800 mg, orally, once daily, through Cycles 1-24 or until disease progression, unacceptable toxicity or withdrawal from the study for other reasons.

Arm type

Experimental

Investigational medicinal product name

Ublituximab

Investigational medicinal product code

Other name

TG-1101

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Ublituximab, 900 mg, was administered as IV infusion

Investigational medicinal product name

Umbralisib

Investigational medicinal product code

Other name

TGR-1202

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Umbralisib, 800 mg, tablet was administered orally

Arm B: Umbralisib (TGR-1202) Monotherapy

Arm description

Subjects with FL, SLL, MZL, MCL, and DLBCL received umbralisib 800 mg orally, once daily through Cycles 1-24 (1 cycle=28 days), or until disease progression, unacceptable toxicity, or withdrawal from the study for other reasons.

Arm type

Experimental

Investigational medicinal product name

Umbralisib

Investigational medicinal product code

Other name

TGR-1202

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Umbralisib, 800 mg, tablet was administered orally

Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine

Arm description

Subjects with DLBCL received ublituximab 900 mg, IV infusion, on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 and, thereafter on Day 1 of every 3 cycles, through Cycle 24 (1 cycle=28 days) in combination with umbralisib, 800 mg orally, once daily through Cycles 1-24 and bendamustine 90 milligrams per square meter (mg/m^2), IV infusion, on Days 1 and 2 of Cycles 1-6 or until disease progression, unacceptable toxicity or withdrawal from the study for other reasons.

Arm type

Experimental

Investigational medicinal product name

Ublituximab

Investigational medicinal product code

Other name

TG-1101

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Ublituximab, 900 mg, was administered as IV infusion

Investigational medicinal product name

Umbralisib

Investigational medicinal product code

Other name

TGR-1202

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Umbralisib, 800 mg, tablet was administered orally

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Treanda

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine, 100 mg, was administered as IV infusion

Arm D: Ublituximab Monotherapy

Arm description

Subjects with FL received ublituximab 900 mg, IV infusion, on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 and, thereafter on Day 1 of every 3 cycles, through Cycle 24 (1 cycle=28 days) or until disease progression, unacceptable toxicity, or withdrawal from the study for other reasons.

Arm type

Experimental

Investigational medicinal product name

Ublituximab

Investigational medicinal product code

Other name

TG-1101

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Ublituximab, 900 mg, was administered as IV infusion

Arm E: Ublituximab to Umbralisib (TGR-1202)

Arm description

Subjects in Arm D were crossed over to umbralisib monotherapy upon confirmation of progressive disease (PD) by the independent review committee (IRC) to receive umbralisib, 800 mg orally, once daily, through Cycles 1-24 (1 cycle=28 days) or until disease progression, unacceptable toxicity, or withdrawal from the study for other reasons.

Arm type

Experimental

Investigational medicinal product name

Umbralisib

Investigational medicinal product code

Other name

TGR-1202

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Umbralisib, 800 mg, tablet was administered orally

Number of subjects in period 1	Arm A: Ublituximab + Umbralisib (TGR-1202)	Arm B: Umbralisib (TGR-1202) Monotherapy	Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine	Arm D: Ublituximab Monotherapy	Arm E: Ublituximab to Umbralisib (TGR-1202)
Started	262	307	130	24	12
Completed	0	0	0	0	0
Not completed	262	307	130	24	12
Adverse Event	5	13	7	-	-
Completion of Protocol Specified Regimen	1	-	1	-	-
Investigator Decision	22	32	10	2	5
Study Terminated by Sponsor	56	32	7	1	1
Withdrawal of Consent	15	19	12	2	-
Unknown/Missing	1	1	-	-	-
Non-compliance with Study	1	1	2	-	-
Death	34	18	13	2	1
Progressive Disease	108	173	73	17	4
Lost to follow-up	1	-	1	-	-
Reason not Specified	6	4	3	-	-
Initiation of Non-protocol Anti-cancer Therapy	10	8	1	-	1
Lack of efficacy	2	6	-	-	-

Baseline characteristics

Top of page

Reporting group title

Arm A: Ublituximab + Umbralisib (TGR-1202)

Reporting group description

Subjects with FL, MZL, MCL, and DLBCL received ublituximab, 900 milligrams (mg), intravenous (IV), infusion on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6, and thereafter on Day 1 of every 3 cycles, through Cycle 24 (1 cycle=28 days) in combination with umbralisib, 800 mg, orally, once daily, through Cycles 1-24 or until disease progression, unacceptable toxicity or withdrawal from the study for other reasons.

Reporting group title

Arm B: Umbralisib (TGR-1202) Monotherapy

Reporting group description

Subjects with FL, SLL, MZL, MCL, and DLBCL received umbralisib 800 mg orally, once daily through Cycles 1-24 (1 cycle=28 days), or until disease progression, unacceptable toxicity, or withdrawal from the study for other reasons.

Reporting group title

Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine

Reporting group description

Subjects with DLBCL received ublituximab 900 mg, IV infusion, on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 and, thereafter on Day 1 of every 3 cycles, through Cycle 24 (1 cycle=28 days) in combination with umbralisib, 800 mg orally, once daily through Cycles 1-24 and bendamustine 90 milligrams per square meter (mg/m^2), IV infusion, on Days 1 and 2 of Cycles 1-6 or until disease progression, unacceptable toxicity or withdrawal from the study for other reasons.

Reporting group title

Arm D: Ublituximab Monotherapy

Reporting group description

Subjects with FL received ublituximab 900 mg, IV infusion, on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 and, thereafter on Day 1 of every 3 cycles, through Cycle 24 (1 cycle=28 days) or until disease progression, unacceptable toxicity, or withdrawal from the study for other reasons.

Reporting group title

Arm E: Ublituximab to Umbralisib (TGR-1202)

Reporting group description

Subjects in Arm D were crossed over to umbralisib monotherapy upon confirmation of progressive disease (PD) by the independent review committee (IRC) to receive umbralisib, 800 mg orally, once daily, through Cycles 1-24 (1 cycle=28 days) or until disease progression, unacceptable toxicity, or withdrawal from the study for other reasons.

Reporting group values	Arm A: Ublituximab + Umbralisib (TGR-1202)	Arm B: Umbralisib (TGR-1202) Monotherapy	Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine	Arm D: Ublituximab Monotherapy	Arm E: Ublituximab to Umbralisib (TGR-1202)	Total
Number of subjects	262	307	130	24	12	735
Age categorical
Units: Subjects
Adults (18-64 years)	87	131	40	13	6	277
From 65-84 years	158	164	79	11	6	418
85 years and over	17	12	11	0	0	40
Age continuous
Units: years
arithmetic mean (standard deviation)	68.4 ( 11.15 )	66.0 ( 11.13 )	69.6 ( 11.25 )	62.9 ( 10.63 )	62.8 ( 10.26 )	-
Gender categorical
Units: Subjects
Female	105	139	52	8	4	308
Male	157	168	78	16	8	427
Race
Units: Subjects
White	211	256	114	19	9	609
Black or African American	8	12	5	1	1	27
Asian	12	10	4	0	0	26
American Indian or Alaska Native	0	2	0	0	0	2
Native Hawaiian or Other Pacific Islander	0	2	0	0	0	2
Multiple	2	0	0	0	0	2
Other	3	5	0	0	0	8
Not Reported	26	20	7	4	2	59
Ethnicity
Units: Subjects
Hispanic or Latino	18	15	2	2	1	38
Not Hispanic or Latino	210	268	115	19	11	623
Not Reported	34	24	13	3	0	74

End points

Top of page

Reporting group title

Arm A: Ublituximab + Umbralisib (TGR-1202)

Reporting group description

Subjects with FL, MZL, MCL, and DLBCL received ublituximab, 900 milligrams (mg), intravenous (IV), infusion on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6, and thereafter on Day 1 of every 3 cycles, through Cycle 24 (1 cycle=28 days) in combination with umbralisib, 800 mg, orally, once daily, through Cycles 1-24 or until disease progression, unacceptable toxicity or withdrawal from the study for other reasons.

Reporting group title

Arm B: Umbralisib (TGR-1202) Monotherapy

Reporting group description

Subjects with FL, SLL, MZL, MCL, and DLBCL received umbralisib 800 mg orally, once daily through Cycles 1-24 (1 cycle=28 days), or until disease progression, unacceptable toxicity, or withdrawal from the study for other reasons.

Reporting group title

Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine

Reporting group description

Subjects with DLBCL received ublituximab 900 mg, IV infusion, on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 and, thereafter on Day 1 of every 3 cycles, through Cycle 24 (1 cycle=28 days) in combination with umbralisib, 800 mg orally, once daily through Cycles 1-24 and bendamustine 90 milligrams per square meter (mg/m^2), IV infusion, on Days 1 and 2 of Cycles 1-6 or until disease progression, unacceptable toxicity or withdrawal from the study for other reasons.

Reporting group title

Arm D: Ublituximab Monotherapy

Reporting group description

Subjects with FL received ublituximab 900 mg, IV infusion, on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 and, thereafter on Day 1 of every 3 cycles, through Cycle 24 (1 cycle=28 days) or until disease progression, unacceptable toxicity, or withdrawal from the study for other reasons.

Reporting group title

Arm E: Ublituximab to Umbralisib (TGR-1202)

Reporting group description

Subjects in Arm D were crossed over to umbralisib monotherapy upon confirmation of progressive disease (PD) by the independent review committee (IRC) to receive umbralisib, 800 mg orally, once daily, through Cycles 1-24 (1 cycle=28 days) or until disease progression, unacceptable toxicity, or withdrawal from the study for other reasons.

Primary: Overall Response Rate (ORR)

Top of page

End point title

Overall Response Rate (ORR) ^[1]

End point description

The ORR was defined as the sum of the percentage of subjects who had complete response (CR) and partial response (PR) and was determined according to the Revised Criteria for Malignant Lymphoma (Cheson 2007). CR was defined as the disappearance of all evidence of disease, spleen &/or liver normal in size, disappearance of all nodules of disease, all lymph nodes and nodal masses in fluorodeoxyglucose (FDG) avid lymphomas regressed to normal size. PR was defined as the regression of measurable disease and no new sites of disease. Regression was ≥ 50% decrease in sum of the products of diameters (SPD) of index lesions, with no unequivocal increase in size of other lymph nodes, liver, or spleen. Data for this endpoint was not collected or analysed as the study was terminated due to the sponsor’s business decision.

End point type

Primary

End point timeframe

Up to approximately 6 years

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Data for this endpoint was not collected or analysed as the study was terminated due to the sponsor’s business decision.

End point values	Arm A: Ublituximab + Umbralisib (TGR-1202)	Arm B: Umbralisib (TGR-1202) Monotherapy	Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine	Arm D: Ublituximab Monotherapy	Arm E: Ublituximab to Umbralisib (TGR-1202)
Number of subjects analysed	0 ^[2]	0 ^[3]	0 ^[4]	0 ^[5]	0 ^[6]
Units: percentage of subjects
number (confidence interval 95%)	( to )	( to )	( to )	( to )	( to )

Notes
[2] - Data was not collected or analysed due to the termination of the study by the sponsor.
[3] - Data was not collected or analysed due to the termination of the study by the sponsor.
[4] - Data was not collected or analysed due to the termination of the study by the sponsor.
[5] - Data was not collected or analysed due to the termination of the study by the sponsor.
[6] - Data was not collected or analysed due to the termination of the study by the sponsor.

No statistical analyses for this end point

Secondary: Progression-Free Survival (PFS)

Top of page

End point title

Progression-Free Survival (PFS)

End point description

PFS was defined as the interval from randomisation to the earlier of the first documentation of definitive disease progression or death from any cause. The appearance of any new lesion more than 1.5 centimeters (cm) in any axis, even if other lesions were decreasing in size was considered relapsed or progressive disease. At least a 50% increase from nadir in one of the following: SPD of index lesions, greatest transverse diameter (GTD) of any individual previously involved node, or GTD of any previously involved node provided that the GTD of that node was ≥ 1.5 cm. Data for this endpoint was not collected or analysed as the study was terminated due to the sponsor’s business decision.

End point type

Secondary

End point timeframe

From date of randomisation until the date of first documented progression or death (up to approximately 6 years)

End point values	Arm A: Ublituximab + Umbralisib (TGR-1202)	Arm B: Umbralisib (TGR-1202) Monotherapy	Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine	Arm D: Ublituximab Monotherapy	Arm E: Ublituximab to Umbralisib (TGR-1202)
Number of subjects analysed	0 ^[7]	0 ^[8]	0 ^[9]	0 ^[10]	0 ^[11]
Units: months
number (confidence interval 95%)	( to )	( to )	( to )	( to )	( to )

Notes
[7] - Data was not collected or analysed due to the termination of the study by the sponsor.
[8] - Data was not collected or analysed due to the termination of the study by the sponsor.
[9] - Data was not collected or analysed due to the termination of the study by the sponsor.
[10] - Data was not collected or analysed due to the termination of the study by the sponsor.
[11] - Data was not collected or analysed due to the termination of the study by the sponsor.

No statistical analyses for this end point

Secondary: Progression-Free Survival (PFS) at Month 6

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End point title

Progression-Free Survival (PFS) at Month 6

End point description

PFS was defined as the percentage of subjects not experiencing progression i.e definitive disease progression or death from any cause by Month 6. The appearance of any new lesion more than 1.5 cm in any axis, even if other lesions were decreasing in size was considered relapsed or progressive disease. At least a 50% increase from nadir in one of the following: SPD of index lesions, GTD of any individual previously involved node, or GTD of any previously involved node provided that the GTD of that node was ≥ 1.5 cm. Data for this endpoint was not collected or analysed as the study was terminated due to the sponsor’s business decision.

End point type

Secondary

End point timeframe

At Month 6

End point values	Arm A: Ublituximab + Umbralisib (TGR-1202)	Arm B: Umbralisib (TGR-1202) Monotherapy	Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine	Arm D: Ublituximab Monotherapy	Arm E: Ublituximab to Umbralisib (TGR-1202)
Number of subjects analysed	0 ^[12]	0 ^[13]	0 ^[14]	0 ^[15]	0 ^[16]
Units: percentage of subjects
number (confidence interval 95%)	( to )	( to )	( to )	( to )	( to )

Notes
[12] - Data was not collected or analysed due to the termination of the study by the sponsor.
[13] - Data was not collected or analysed due to the termination of the study by the sponsor.
[14] - Data was not collected or analysed due to the termination of the study by the sponsor.
[15] - Data was not collected or analysed due to the termination of the study by the sponsor.
[16] - Data was not collected or analysed due to the termination of the study by the sponsor.

No statistical analyses for this end point

Secondary: Complete Response (CR) Rate

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End point title

Complete Response (CR) Rate

End point description

CR rate is defined as the percentage of subjects who achieve a CR as determined according to the Revised Criteria for Malignant Lymphoma (Cheson 2007). CR was defined as the disappearance of all evidence of disease, spleen &/or liver normal in size, disappearance of all nodules of disease, all lymph nodes and nodal masses in FDG-avid lymphomas regressed to normal size. Data for this endpoint was not collected or analysed as the study was terminated due to the sponsor’s business decision.

End point type

Secondary

End point timeframe

Up to approximately 6 years

End point values	Arm A: Ublituximab + Umbralisib (TGR-1202)	Arm B: Umbralisib (TGR-1202) Monotherapy	Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine	Arm D: Ublituximab Monotherapy	Arm E: Ublituximab to Umbralisib (TGR-1202)
Number of subjects analysed	0 ^[17]	0 ^[18]	0 ^[19]	0 ^[20]	0 ^[21]
Units: percentage of subjects
number (confidence interval 95%)	( to )	( to )	( to )	( to )	( to )

Notes
[17] - Data was not collected or analysed due to the termination of the study by the sponsor.
[18] - Data was not collected or analysed due to the termination of the study by the sponsor.
[19] - Data was not collected or analysed due to the termination of the study by the sponsor.
[20] - Data was not collected or analysed due to the termination of the study by the sponsor.
[21] - Data was not collected or analysed due to the termination of the study by the sponsor.

No statistical analyses for this end point

Secondary: Overall Survival (OS)

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End point title

Overall Survival (OS)

End point description

OS is defined as the interval from randomisation to death from any cause. Data for this endpoint was not collected or analysed as the study was terminated due to the sponsor’s business decision.

End point type

Secondary

End point timeframe

Up to approximately 6 years

End point values	Arm A: Ublituximab + Umbralisib (TGR-1202)	Arm B: Umbralisib (TGR-1202) Monotherapy	Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine	Arm D: Ublituximab Monotherapy	Arm E: Ublituximab to Umbralisib (TGR-1202)
Number of subjects analysed	0 ^[22]	0 ^[23]	0 ^[24]	0 ^[25]	0 ^[26]
Units: months
number (confidence interval 95%)	( to )	( to )	( to )	( to )	( to )

Notes
[22] - Data was not collected or analysed due to the termination of the study by the sponsor.
[23] - Data was not collected or analysed due to the termination of the study by the sponsor.
[24] - Data was not collected or analysed due to the termination of the study by the sponsor.
[25] - Data was not collected or analysed due to the termination of the study by the sponsor.
[26] - Data was not collected or analysed due to the termination of the study by the sponsor.

No statistical analyses for this end point

Secondary: Duration of Response (DOR)

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End point title

Duration of Response (DOR)

End point description

DOR is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause.CR=disappearance of all evidence of disease, spleen &/or liver normal in size, disappearance of all nodules of disease, all lymph nodes and nodal masses in FDG-avid lymphomas regressed to normal size.PR=regression of measurable disease and no new sites of disease. Regression=≥ 50% decrease in SPD of index lesions, with no unequivocal increase in size of other lymph nodes, liver, or spleen.PD=appearance of any new lesion more than 1.5 cm in any axis, even if other lesions were decreasing in size. At least a 50% increase from nadir in one of the following: SPD of index lesions, GTD of any individual previously involved node, or GTD of any previously involved node provided that the GTD of that node was ≥ 1.5 cm. Data for this endpoint was not collected/analysed as the study was terminated due to the sponsor's decision.

End point type

Secondary

End point timeframe

Up to approximately 6 years

End point values	Arm A: Ublituximab + Umbralisib (TGR-1202)	Arm B: Umbralisib (TGR-1202) Monotherapy	Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine	Arm D: Ublituximab Monotherapy	Arm E: Ublituximab to Umbralisib (TGR-1202)
Number of subjects analysed	0 ^[27]	0 ^[28]	0 ^[29]	0 ^[30]	0 ^[31]
Units: months
median (full range (min-max))	( to )	( to )	( to )	( to )	( to )

Notes
[27] - Data was not collected or analysed due to the termination of the study by the sponsor.
[28] - Data was not collected or analysed due to the termination of the study by the sponsor.
[29] - Data was not collected or analysed due to the termination of the study by the sponsor.
[30] - Data was not collected or analysed due to the termination of the study by the sponsor.
[31] - Data was not collected or analysed due to the termination of the study by the sponsor.

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs)

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End point title

Number of Subjects With Treatment Emergent Adverse Events (TEAEs)

End point description

An adverse event (AE) is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product. An AE does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is any AE that occur after first dosing of study medication and through the end of the study or through 30 days after the last dose of study treatment, or is considered treatment-related regardless of the start date of the event, or is present before first dosing of study medication but worsens in intensity or the investigator subsequently considers treatment-related. Safety Population included all subjects who were enrolled and received at least one dose of the study drug.

End point type

Secondary

End point timeframe

Up to approximately 6 years

End point values	Arm A: Ublituximab + Umbralisib (TGR-1202)	Arm B: Umbralisib (TGR-1202) Monotherapy	Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine	Arm D: Ublituximab Monotherapy	Arm E: Ublituximab to Umbralisib (TGR-1202)
Number of subjects analysed	262	307	130	24	12
Units: Subjects	255	303	127	21	12

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From signing of informed consent until 30 days after last dose of study drug (up to approximately 6 years)

Adverse event reporting additional description

Safety Population included all subjects who were enrolled and received at least one dose of the study drug.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Arm A: Ublituximab + Umbralisib (TGR-1202)

Reporting group description

Subjects with FL, MZL, MCL, and DLBCL received ublituximab, 900 mg, IV, infusion on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6, and thereafter on Day 1 of every 3 cycles, through Cycle 24 (1 cycle=28 days) in combination with umbralisib, 800 mg, orally, once daily, through Cycles 1-24 or until disease progression, unacceptable toxicity or withdrawal from the study for other reasons.

Reporting group title

Arm B: Umbralisib (TGR-1202) Monotherapy

Reporting group description

Subjects with FL, SLL, MZL, MCL, and DLBCL received umbralisib 800 mg orally, once daily through Cycles 1-24 (1 cycle=28 days), or until disease progression, unacceptable toxicity, or withdrawal from the study for other reasons.

Reporting group title

Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine

Reporting group description

Subjects with DLBCL received ublituximab 900 mg, IV infusion, on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 and, thereafter on Day 1 of every 3 cycles, through Cycle 24 (1 cycle=28 days) in combination with umbralisib, 800 mg orally, once daily through Cycles 1-24 and bendamustine 90 mg/m^2, IV infusion, on Days 1 and 2 of Cycles 1-6 or until disease progression, unacceptable toxicity or withdrawal from the study for other reasons.

Reporting group title

Arm D: Ublituximab Monotherapy

Reporting group description

Subjects with FL received ublituximab 900 mg, IV infusion, on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 and, thereafter on Day 1 of every 3 cycles, through Cycle 24 (1 cycle=28 days) or until disease progression, unacceptable toxicity, or withdrawal from the study for other reasons.

Reporting group title

Arm E: Ublituximab to Umbralisib (TGR-1202)

Reporting group description

Subjects in Arm D were crossed over to umbralisib monotherapy upon confirmation of PD by the IRC to receive umbralisib, 800 mg orally, once daily, through Cycles 1-24 (1 cycle=28 days) or until disease progression, unacceptable toxicity, or withdrawal from the study for other reasons.

Serious adverse events	Arm A: Ublituximab + Umbralisib (TGR-1202)	Arm B: Umbralisib (TGR-1202) Monotherapy	Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine	Arm D: Ublituximab Monotherapy	Arm E: Ublituximab to Umbralisib (TGR-1202)
Total subjects affected by serious adverse events
subjects affected / exposed	108 / 262 (41.22%)	106 / 307 (34.53%)	63 / 130 (48.46%)	5 / 24 (20.83%)	5 / 12 (41.67%)
number of deaths (all causes)	73	54	88	2	2
number of deaths resulting from adverse events	3	2	2	1	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Breast cancer recurrent
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal adenocarcinoma
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infected neoplasm
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intraductal proliferative breast lesion
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Invasive ductal breast carcinoma
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neuroendocrine carcinoma of the skin
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal cancer
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Extranodal marginal zone B-cell lymphoma (MALT type)
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal neoplasm
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Glioma
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lymphoma
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant melanoma in situ
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myelodysplastic syndrome
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of lung
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Superficial spreading melanoma stage unspecified
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypotension
subjects affected / exposed	3 / 262 (1.15%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Embolism
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Circulatory collapse
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Alcohol detoxification
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Catheter placement
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fluid replacement
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hip arthroplasty
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Incarcerated hernia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Multiple organ dysfunction syndrome
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	5 / 130 (3.85%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 4	4 / 8	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthenia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypothermia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Vaginal fistula
subjects affected / exposed ^[1]	1 / 105 (0.95%)	0 / 139 (0.00%)	0 / 52 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Penile pain
subjects affected / exposed ^[2]	0 / 157 (0.00%)	1 / 168 (0.60%)	0 / 78 (0.00%)	0 / 16 (0.00%)	0 / 8 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	4 / 262 (1.53%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 4	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	3 / 262 (1.15%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	1 / 262 (0.38%)	4 / 307 (1.30%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 4	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	1 / 262 (0.38%)	4 / 307 (1.30%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	2 / 4	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary congestion
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute respiratory distress syndrome
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cough
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Confusional state
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bipolar disorder
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood bilirubin increased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	4 / 262 (1.53%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	4 / 4	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arterial injury
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Alcohol poisoning
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthropod bite
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Brain contusion
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Contusion
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic fracture
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal fracture
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Splenic rupture
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac failure
subjects affected / exposed	4 / 262 (1.53%)	2 / 307 (0.65%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	2 / 5	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardio-respiratory arrest
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute left ventricular failure
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aortic valve disease
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiopulmonary failure
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ventricular failure
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute coronary syndrome
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac tamponade
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 262 (0.00%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stress cardiomyopathy
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Supraventricular tachycardia
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Seizure
subjects affected / exposed	3 / 262 (1.15%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	2 / 4	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyporeflexia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lethargy
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dementia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Febrile neutropenia
subjects affected / exposed	5 / 262 (1.91%)	3 / 307 (0.98%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	4 / 5	3 / 3	3 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	2 / 2	3 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anaemia
subjects affected / exposed	1 / 262 (0.38%)	4 / 307 (1.30%)	5 / 130 (3.85%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	2 / 4	3 / 7	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Agranulocytosis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune haemolytic anaemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemolytic anaemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Diplopia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Optic ischaemic neuropathy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Visual impairment
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Colitis
subjects affected / exposed	4 / 262 (1.53%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	4 / 4	1 / 2	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	4 / 262 (1.53%)	10 / 307 (3.26%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	2 / 4	10 / 12	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune colitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bezoar
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastric haemorrhage
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastric perforation
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal obstruction
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastric ulcer
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestinal haemorrhage
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	6 / 130 (4.62%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	4 / 6	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal stenosis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Autoimmune hepatitis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic failure
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
Hepatic vein thrombosis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis acute
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Portal vein occlusion
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis exfoliative generalised
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Photosensitivity reaction
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rash
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rash pruritic
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urticaria
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	4 / 262 (1.53%)	5 / 307 (1.63%)	3 / 130 (2.31%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 4	2 / 5	1 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal colic
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematuria
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Flank pain
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pathological fracture
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neck pain
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Necrotising myositis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	4 / 262 (1.53%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	2 / 4	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19
subjects affected / exposed	13 / 262 (4.96%)	2 / 307 (0.65%)	2 / 130 (1.54%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 13	0 / 2	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	11 / 262 (4.20%)	10 / 307 (3.26%)	4 / 130 (3.08%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	3 / 14	6 / 11	2 / 5	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	9 / 262 (3.44%)	12 / 307 (3.91%)	2 / 130 (1.54%)	1 / 24 (4.17%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	2 / 9	2 / 12	1 / 2	1 / 1	0 / 1
deaths causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0
Sepsis
subjects affected / exposed	7 / 262 (2.67%)	4 / 307 (1.30%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 7	6 / 8	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis perforated
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopulmonary aspergillosis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Campylobacter infection
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis infectious
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal candidiasis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia cytomegaloviral
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia haemophilus
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pseudomonas infection
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 3	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis pneumococcal
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Corneal infection
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cytomegalovirus infection reactivation
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Empyema
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia bacteraemia
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis aseptic
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenic sepsis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumocystis jirovecii pneumonia
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia legionella
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia serratia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Soft tissue infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Streptococcal sepsis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Tumour lysis syndrome
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	1 / 262 (0.38%)	5 / 307 (1.63%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	2 / 5	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fluid overload
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tetany
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cachexia
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypocalcaemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypophosphataemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the male population in this study.

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

Non-serious adverse events	Arm A: Ublituximab + Umbralisib (TGR-1202)	Arm B: Umbralisib (TGR-1202) Monotherapy	Arm C: Ublituximab + Umbralisib (TGR-1202) + Bendamustine	Arm D: Ublituximab Monotherapy	Arm E: Ublituximab to Umbralisib (TGR-1202)
Total subjects affected by non serious adverse events
subjects affected / exposed	254 / 262 (96.95%)	303 / 307 (98.70%)	125 / 130 (96.15%)	20 / 24 (83.33%)	12 / 12 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	5 / 262 (1.91%)	1 / 307 (0.33%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	6	1	0	1	0
Lipoma
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	0	0	0
Benign neoplasm of eye
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Bowen's disease
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Central nervous system lymphoma
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Haemangioma of skin
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Meningioma
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Neoplasm skin
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Seborrhoeic keratosis
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Skin cancer
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Squamous cell carcinoma of head and neck
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0
Tumour pain
subjects affected / exposed	1 / 262 (0.38%)	4 / 307 (1.30%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	4	4	0	0
Cancer pain
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	2	0	0
Gastrointestinal tract adenoma
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Haemangioma
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Neoplasm
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Oral neoplasm
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Skin neoplasm bleeding
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	1
Squamous cell carcinoma
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	0	1	0	1	0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Vascular disorders
Hypertension
subjects affected / exposed	20 / 262 (7.63%)	23 / 307 (7.49%)	2 / 130 (1.54%)	3 / 24 (12.50%)	0 / 12 (0.00%)
occurrences all number	29	34	2	5	0
Flushing
subjects affected / exposed	10 / 262 (3.82%)	4 / 307 (1.30%)	2 / 130 (1.54%)	3 / 24 (12.50%)	0 / 12 (0.00%)
occurrences all number	11	4	2	3	0
Hypotension
subjects affected / exposed	7 / 262 (2.67%)	10 / 307 (3.26%)	13 / 130 (10.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	12	19	0	0
Hot flush
subjects affected / exposed	5 / 262 (1.91%)	18 / 307 (5.86%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	19	1	0	0
Deep vein thrombosis
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	2	0	0
Haematoma
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	2	2	0	0	1
Lymphoedema
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Thrombophlebitis superficial
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	2	0	0
Arterial thrombosis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Embolism
subjects affected / exposed	0 / 262 (0.00%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	1	0	0
Embolism venous
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Haemorrhage
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Hyperaemia
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Pallor
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Peripheral coldness
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Peripheral venous disease
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Subgaleal haematoma
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Varicose vein
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Vascular insufficiency
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Vasculitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Surgical and medical procedures
Skin neoplasm excision
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	0	0
Hip arthroplasty
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Tooth extraction
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Cancer surgery
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Cataract operation
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Cerumen removal
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Knee arthroplasty
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	80 / 262 (30.53%)	96 / 307 (31.27%)	49 / 130 (37.69%)	5 / 24 (20.83%)	3 / 12 (25.00%)
occurrences all number	109	133	71	5	3
Oedema peripheral
subjects affected / exposed	35 / 262 (13.36%)	35 / 307 (11.40%)	15 / 130 (11.54%)	4 / 24 (16.67%)	2 / 12 (16.67%)
occurrences all number	43	51	19	5	2
Pyrexia
subjects affected / exposed	32 / 262 (12.21%)	37 / 307 (12.05%)	17 / 130 (13.08%)	3 / 24 (12.50%)	2 / 12 (16.67%)
occurrences all number	37	63	29	3	2
Asthenia
subjects affected / exposed	25 / 262 (9.54%)	29 / 307 (9.45%)	14 / 130 (10.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	30	37	20	0	0
Chills
subjects affected / exposed	23 / 262 (8.78%)	22 / 307 (7.17%)	6 / 130 (4.62%)	2 / 24 (8.33%)	0 / 12 (0.00%)
occurrences all number	32	27	6	3	0
Non-cardiac chest pain
subjects affected / exposed	9 / 262 (3.44%)	5 / 307 (1.63%)	1 / 130 (0.77%)	2 / 24 (8.33%)	0 / 12 (0.00%)
occurrences all number	9	6	1	2	0
Pain
subjects affected / exposed	9 / 262 (3.44%)	7 / 307 (2.28%)	6 / 130 (4.62%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	9	7	6	0	0
Chest discomfort
subjects affected / exposed	6 / 262 (2.29%)	3 / 307 (0.98%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	6	4	3	0	0
Peripheral swelling
subjects affected / exposed	6 / 262 (2.29%)	10 / 307 (3.26%)	4 / 130 (3.08%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	8	11	4	1	0
Feeling abnormal
subjects affected / exposed	4 / 262 (1.53%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	5	0	0	0
Influenza like illness
subjects affected / exposed	4 / 262 (1.53%)	4 / 307 (1.30%)	3 / 130 (2.31%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	5	4	3	1	0
Swelling
subjects affected / exposed	4 / 262 (1.53%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	3	0	0	0
Catheter site pain
subjects affected / exposed	3 / 262 (1.15%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	2	0	0	0
Chest pain
subjects affected / exposed	3 / 262 (1.15%)	8 / 307 (2.61%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	8	3	0	0
Face oedema
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	2	0	0
Feeling hot
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	2	0	0	1	0
Gait disturbance
subjects affected / exposed	2 / 262 (0.76%)	3 / 307 (0.98%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	3	2	0	0
Localised oedema
subjects affected / exposed	2 / 262 (0.76%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	3	1	0	0
Malaise
subjects affected / exposed	2 / 262 (0.76%)	7 / 307 (2.28%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	8	0	0	0
Swelling face
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Administration site extravasation
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Adverse drug reaction
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Axillary pain
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	1	2	0	1	0
Catheter site swelling
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Discomfort
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0
Early satiety
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	1	0	0
Facial pain
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Feeling jittery
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	1	0	0
Illness
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Injection site bruising
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Mucosal inflammation
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	1	0	0
Oedema
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	1	1	0	1	0
Performance status decreased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Disease progression
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Drug intolerance
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Exercise tolerance decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Feeling cold
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
General physical health deterioration
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Generalised oedema
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Mass
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Mucosal hyperaemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Nodule
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Sensation of foreign body
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Temperature intolerance
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Tenderness
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Thirst
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Tissue infiltration
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	5 / 262 (1.91%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	6	0	2	0	0
Seasonal allergy
subjects affected / exposed	3 / 262 (1.15%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	3	0	0	0
Drug hypersensitivity
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	4	0	0	0
Hypogammaglobulinaemia
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	1	0	0
Allergy to animal
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Contrast media allergy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Contrast media reaction
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Immunodeficiency
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Sarcoidosis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Reproductive system and breast disorders
Scrotal oedema
subjects affected / exposed ^[3]	2 / 157 (1.27%)	0 / 168 (0.00%)	0 / 78 (0.00%)	0 / 16 (0.00%)	0 / 8 (0.00%)
occurrences all number	2	0	0	0	0
Oedema genital
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Pelvic pain
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Vulvovaginal pain
subjects affected / exposed ^[4]	1 / 105 (0.95%)	0 / 139 (0.00%)	0 / 52 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	0	0
Benign prostatic hyperplasia
subjects affected / exposed ^[5]	0 / 157 (0.00%)	2 / 168 (1.19%)	1 / 78 (1.28%)	0 / 16 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	2	1	0	0
Breast discolouration
subjects affected / exposed ^[6]	0 / 105 (0.00%)	1 / 139 (0.72%)	0 / 52 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Breast mass
subjects affected / exposed ^[7]	0 / 105 (0.00%)	0 / 139 (0.00%)	1 / 52 (1.92%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Breast oedema
subjects affected / exposed ^[8]	0 / 105 (0.00%)	1 / 139 (0.72%)	0 / 52 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Breast pain
subjects affected / exposed ^[9]	0 / 105 (0.00%)	2 / 139 (1.44%)	1 / 52 (1.92%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	1	0	0
Breast swelling
subjects affected / exposed ^[10]	0 / 105 (0.00%)	1 / 139 (0.72%)	0 / 52 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Genital lesion
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Genital rash
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Gynaecomastia
subjects affected / exposed ^[11]	0 / 105 (0.00%)	1 / 139 (0.72%)	0 / 52 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Menstruation irregular
subjects affected / exposed ^[12]	0 / 105 (0.00%)	0 / 139 (0.00%)	0 / 52 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	1
Orchitis noninfective
subjects affected / exposed ^[13]	0 / 157 (0.00%)	1 / 168 (0.60%)	0 / 78 (0.00%)	0 / 16 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0
Peyronie's disease
subjects affected / exposed ^[14]	0 / 157 (0.00%)	0 / 168 (0.00%)	1 / 78 (1.28%)	0 / 16 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0
Testicular oedema
subjects affected / exposed ^[15]	0 / 157 (0.00%)	1 / 168 (0.60%)	0 / 78 (0.00%)	0 / 16 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0
Testicular pain
subjects affected / exposed ^[16]	0 / 157 (0.00%)	1 / 168 (0.60%)	1 / 78 (1.28%)	0 / 16 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	1	0	0
Vaginal haemorrhage
subjects affected / exposed ^[17]	0 / 105 (0.00%)	0 / 139 (0.00%)	2 / 52 (3.85%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	0
Vulvovaginal dryness
subjects affected / exposed ^[18]	0 / 105 (0.00%)	0 / 139 (0.00%)	1 / 52 (1.92%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Vulvovaginal pruritus
subjects affected / exposed ^[19]	0 / 105 (0.00%)	0 / 139 (0.00%)	1 / 52 (1.92%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	41 / 262 (15.65%)	33 / 307 (10.75%)	18 / 130 (13.85%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	48	37	23	1	0
Cough
subjects affected / exposed	32 / 262 (12.21%)	57 / 307 (18.57%)	17 / 130 (13.08%)	5 / 24 (20.83%)	2 / 12 (16.67%)
occurrences all number	46	78	26	8	2
Oropharyngeal pain
subjects affected / exposed	10 / 262 (3.82%)	13 / 307 (4.23%)	5 / 130 (3.85%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	10	13	5	1	0
Pleural effusion
subjects affected / exposed	7 / 262 (2.67%)	11 / 307 (3.58%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	13	17	0	0
Productive cough
subjects affected / exposed	7 / 262 (2.67%)	9 / 307 (2.93%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	8	11	2	0	0
Dysphonia
subjects affected / exposed	6 / 262 (2.29%)	4 / 307 (1.30%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	6	4	1	0	0
Nasal congestion
subjects affected / exposed	5 / 262 (1.91%)	9 / 307 (2.93%)	3 / 130 (2.31%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	5	11	3	2	0
Chronic obstructive pulmonary disease
subjects affected / exposed	4 / 262 (1.53%)	0 / 307 (0.00%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	3	0	0
Epistaxis
subjects affected / exposed	3 / 262 (1.15%)	7 / 307 (2.28%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	7	3	0	0
Hypoxia
subjects affected / exposed	3 / 262 (1.15%)	6 / 307 (1.95%)	2 / 130 (1.54%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	3	6	2	1	0
Pulmonary oedema
subjects affected / exposed	3 / 262 (1.15%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	1	0	0	0
Respiratory tract congestion
subjects affected / exposed	3 / 262 (1.15%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0
Rhinitis allergic
subjects affected / exposed	3 / 262 (1.15%)	4 / 307 (1.30%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	5	3	0	0
Upper-airway cough syndrome
subjects affected / exposed	3 / 262 (1.15%)	5 / 307 (1.63%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	5	2	0	0
Wheezing
subjects affected / exposed	3 / 262 (1.15%)	4 / 307 (1.30%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	3	4	0	2	0
Dyspnoea exertional
subjects affected / exposed	2 / 262 (0.76%)	6 / 307 (1.95%)	4 / 130 (3.08%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	2	6	6	1	0
Haemoptysis
subjects affected / exposed	2 / 262 (0.76%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	3	1	0	0
Hiccups
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0
Rhinorrhoea
subjects affected / exposed	2 / 262 (0.76%)	5 / 307 (1.63%)	4 / 130 (3.08%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	5	5	0	0
Throat irritation
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	1	0	0
Atelectasis
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Dry throat
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0
Interstitial lung disease
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	4	0	0	0
Nasal obstruction
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0
Nasal pruritus
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Nasal ulcer
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Oropharyngeal swelling
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Paranasal sinus discomfort
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Pleurisy
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Pneumonitis
subjects affected / exposed	1 / 262 (0.38%)	5 / 307 (1.63%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	5	1	0	0
Pulmonary embolism
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	1	1	0	2	0
Pulmonary hypertension
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Pulmonary mass
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Rales
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	4	0	0	0
Sinus congestion
subjects affected / exposed	1 / 262 (0.38%)	7 / 307 (2.28%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	7	1	0	0
Sinus pain
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	1	3	0	1	0
Sleep apnoea syndrome
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	3	0	0	0
Throat tightness
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Acute respiratory failure
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	1	0	0
Aspiration
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0
Asthma
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Bronchial hyperreactivity
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Bronchial obstruction
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Catarrh
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Laryngeal inflammation
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Mediastinal shift
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Nasal dryness
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Nasal mucosal ulcer
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Nasal oedema
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Nasal polyps
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Nasal septum disorder
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Paranasal sinus hypersecretion
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Pharyngeal erythema
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Pharyngeal hypertrophy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Pleuritic pain
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Pneumothorax
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	1	0	0
Respiration abnormal
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	1
Respiratory failure
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Respiratory tract inflammation
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Rhinalgia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Rhonchi
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Snoring
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Sputum increased
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Vasomotor rhinitis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	28 / 262 (10.69%)	40 / 307 (13.03%)	19 / 130 (14.62%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	33	45	25	1	0
Anxiety
subjects affected / exposed	14 / 262 (5.34%)	8 / 307 (2.61%)	7 / 130 (5.38%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	15	9	7	1	0
Agitation
subjects affected / exposed	6 / 262 (2.29%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	6	2	2	0	0
Confusional state
subjects affected / exposed	6 / 262 (2.29%)	16 / 307 (5.21%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	6	16	1	0	0
Depression
subjects affected / exposed	5 / 262 (1.91%)	13 / 307 (4.23%)	4 / 130 (3.08%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	5	13	4	0	1
Restlessness
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	2	0	0
Sleep disorder
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	0	0	0
Delirium
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Depressed mood
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	4	0	0	0
Euphoric mood
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Irritability
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Mood swings
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Nightmare
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	1	0	0
Poor quality sleep
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Abnormal dreams
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Affect lability
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Bruxism
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Disorientation
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Emotional disorder
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Hallucination
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Mania
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Mental status changes
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	1	0	0
Mood altered
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Nervousness
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Panic attack
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Self-induced vomiting
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	0	0	0
Product issues
Device leakage
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Device breakage
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Device occlusion
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	2	0	0
Thrombosis in device
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	1
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Hepatic necrosis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Hepatitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Hepatocellular injury
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0
Bile duct obstruction
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Cholecystitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Gallbladder polyp
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Hepatic cirrhosis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Hepatic steatosis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Hepatitis acute
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Hyperbilirubinaemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Liver disorder
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	40 / 262 (15.27%)	51 / 307 (16.61%)	14 / 130 (10.77%)	1 / 24 (4.17%)	1 / 12 (8.33%)
occurrences all number	80	81	23	1	4
Alanine aminotransferase increased
subjects affected / exposed	38 / 262 (14.50%)	53 / 307 (17.26%)	13 / 130 (10.00%)	1 / 24 (4.17%)	1 / 12 (8.33%)
occurrences all number	96	107	20	1	7
Neutrophil count decreased
subjects affected / exposed	23 / 262 (8.78%)	21 / 307 (6.84%)	17 / 130 (13.08%)	1 / 24 (4.17%)	2 / 12 (16.67%)
occurrences all number	76	33	31	2	6
Blood creatinine increased
subjects affected / exposed	17 / 262 (6.49%)	38 / 307 (12.38%)	5 / 130 (3.85%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	29	52	6	0	1
Blood lactate dehydrogenase increased
subjects affected / exposed	14 / 262 (5.34%)	5 / 307 (1.63%)	6 / 130 (4.62%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	14	5	7	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	12 / 262 (4.58%)	14 / 307 (4.56%)	9 / 130 (6.92%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	14	20	14	0	0
Weight decreased
subjects affected / exposed	12 / 262 (4.58%)	24 / 307 (7.82%)	14 / 130 (10.77%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	15	32	19	1	0
Blood bilirubin increased
subjects affected / exposed	9 / 262 (3.44%)	8 / 307 (2.61%)	5 / 130 (3.85%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	16	14	9	0	0
Platelet count decreased
subjects affected / exposed	9 / 262 (3.44%)	16 / 307 (5.21%)	12 / 130 (9.23%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	17	28	27	1	0
White blood cell count decreased
subjects affected / exposed	9 / 262 (3.44%)	7 / 307 (2.28%)	9 / 130 (6.92%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	16	10	25	0	0
Weight increased
subjects affected / exposed	7 / 262 (2.67%)	5 / 307 (1.63%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	9	7	0	0
Lymphocyte count decreased
subjects affected / exposed	4 / 262 (1.53%)	6 / 307 (1.95%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	9	8	5	0	0
Blood magnesium decreased
subjects affected / exposed	3 / 262 (1.15%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	1	0	0	0
Blood pressure increased
subjects affected / exposed	3 / 262 (1.15%)	4 / 307 (1.30%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	5	3	0	0
C-reactive protein increased
subjects affected / exposed	3 / 262 (1.15%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	2	0	0	0
Hepatic enzyme increased
subjects affected / exposed	3 / 262 (1.15%)	0 / 307 (0.00%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	5	0	0	1	0
Blood uric acid increased
subjects affected / exposed	2 / 262 (0.76%)	4 / 307 (1.30%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	4	0	0	0
Ejection fraction decreased
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	1	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	2	0	0	0
Glomerular filtration rate
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	1	0	0
Ammonia increased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Blood albumin decreased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Blood bicarbonate decreased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Blood calcium increased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Blood cholesterol increased
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	3	1	0	0
Blood glucose increased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Blood immunoglobulin G decreased
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Blood urea increased
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Blood urine present
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Cardiac murmur
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	3	1	0	0
Clostridium test positive
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Coronavirus test positive
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Cytomegalovirus test positive
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
ECG signs of myocardial ischaemia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Electrocardiogram QT prolonged
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Haemoglobin decreased
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Hepatic enzyme abnormal
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Immunoglobulins decreased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Liver function test increased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Magnetic resonance imaging brain abnormal
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Prostatic specific antigen increased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Prothrombin time prolonged
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Red blood cell sedimentation rate increased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Transaminases increased
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	4	1	0	0
Troponin increased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Urinary sediment present
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Vitamin B12 decreased
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Beta globulin decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	2	0	0
Blood immunoglobulin A decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Blood immunoglobulin M increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Blood iron decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Blood potassium decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Blood prolactin increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Blood testosterone decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Blood viscosity increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Body temperature decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	4	0	0	0
Body temperature increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Bone density decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Breath sounds abnormal
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Eastern Cooperative Oncology Group performance status worsened
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Faecal calprotectin increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Haemoglobin increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Haemophilus test positive
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Heart rate increased
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Human rhinovirus positive
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Immature granulocyte count increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Immunoglobulins increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
International normalised ratio increased
subjects affected / exposed	0 / 262 (0.00%)	4 / 307 (1.30%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	7	0	0	0
Light chain analysis decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Light chain analysis increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Lipase increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	3	0	0
Low density lipoprotein increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Lymphocyte count abnormal
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Lymphocyte count increased
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	0	0	0
Monocyte count decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Neutrophil count increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Pedal pulse decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Platelet count increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Protein total decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Protein urine present
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Red cell distribution width increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
SARS-CoV-2 test positive
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	2	0	0	1
Serum ferritin decreased
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Troponin I increased
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Vitamin D decreased
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	2	0	0
White blood cell count increased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	30 / 262 (11.45%)	2 / 307 (0.65%)	4 / 130 (3.08%)	3 / 24 (12.50%)	0 / 12 (0.00%)
occurrences all number	35	2	5	5	0
Fall
subjects affected / exposed	15 / 262 (5.73%)	17 / 307 (5.54%)	11 / 130 (8.46%)	1 / 24 (4.17%)	1 / 12 (8.33%)
occurrences all number	16	19	12	1	1
Skin laceration
subjects affected / exposed	3 / 262 (1.15%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	2	0	0
Limb injury
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Procedural pain
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	0	0	0
Accidental overdose
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Arthropod bite
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	0 / 130 (0.00%)	1 / 24 (4.17%)	1 / 12 (8.33%)
occurrences all number	1	3	0	1	1
Arthropod sting
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Lumbar vertebral fracture
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Radius fracture
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Rib fracture
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Skin abrasion
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	2	0	0
Thoracic vertebral fracture
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Traumatic intracranial haematoma
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Wound secretion
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Ankle fracture
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Compression fracture
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Concussion
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	1
Foreign body in ear
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Hand fracture
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Head injury
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Hip fracture
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	2	0	0
Joint injury
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Lip injury
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Meniscus injury
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Muscle strain
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Overdose
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Periorbital haematoma
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Procedural hypotension
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Product administration error
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Skin injury
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0
Spinal compression fracture
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Spinal fracture
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Splenic injury
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Stress fracture
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Subdural haematoma
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Tendon rupture
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Thermal burn
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Tibia fracture
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Wound complication
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Congenital, familial and genetic disorders
Phimosis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Cardiac disorders
Tachycardia
subjects affected / exposed	9 / 262 (3.44%)	8 / 307 (2.61%)	7 / 130 (5.38%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	10	8	7	0	0
Atrial fibrillation
subjects affected / exposed	4 / 262 (1.53%)	5 / 307 (1.63%)	5 / 130 (3.85%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	6	5	0	0
Palpitations
subjects affected / exposed	4 / 262 (1.53%)	4 / 307 (1.30%)	5 / 130 (3.85%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	9	4	5	0	0
Angina pectoris
subjects affected / exposed	3 / 262 (1.15%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	3	0	0	0
Cardiac failure
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Pericardial effusion
subjects affected / exposed	2 / 262 (0.76%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	3	1	0	0
Sinus tachycardia
subjects affected / exposed	2 / 262 (0.76%)	5 / 307 (1.63%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	6	2	0	0
Atrial tachycardia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Atrioventricular block complete
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Atrioventricular block second degree
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Cardiac failure congestive
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Cardiomyopathy
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Coronary artery disease
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Sinus bradycardia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Ventricular extrasystoles
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Aortic valve incompetence
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Arrhythmia
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	2	0	0
Bradycardia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Cardiovascular insufficiency
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Extrasystoles
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Mitral valve incompetence
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Pericarditis constrictive
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Supraventricular tachycardia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Nervous system disorders
Headache
subjects affected / exposed	49 / 262 (18.70%)	50 / 307 (16.29%)	15 / 130 (11.54%)	2 / 24 (8.33%)	0 / 12 (0.00%)
occurrences all number	67	81	18	2	0
Dizziness
subjects affected / exposed	44 / 262 (16.79%)	51 / 307 (16.61%)	16 / 130 (12.31%)	4 / 24 (16.67%)	3 / 12 (25.00%)
occurrences all number	50	63	21	4	3
Dysgeusia
subjects affected / exposed	19 / 262 (7.25%)	27 / 307 (8.79%)	8 / 130 (6.15%)	1 / 24 (4.17%)	1 / 12 (8.33%)
occurrences all number	19	29	10	1	1
Paraesthesia
subjects affected / exposed	14 / 262 (5.34%)	10 / 307 (3.26%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	20	15	0	0	0
Tremor
subjects affected / exposed	13 / 262 (4.96%)	14 / 307 (4.56%)	9 / 130 (6.92%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	15	16	16	0	1
Neuropathy peripheral
subjects affected / exposed	7 / 262 (2.67%)	7 / 307 (2.28%)	3 / 130 (2.31%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	7	7	3	1	0
Somnolence
subjects affected / exposed	6 / 262 (2.29%)	8 / 307 (2.61%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	6	10	1	0	0
Memory impairment
subjects affected / exposed	5 / 262 (1.91%)	7 / 307 (2.28%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	8	2	0	0
Peripheral sensory neuropathy
subjects affected / exposed	5 / 262 (1.91%)	6 / 307 (1.95%)	6 / 130 (4.62%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	5	6	8	1	0
Syncope
subjects affected / exposed	3 / 262 (1.15%)	5 / 307 (1.63%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	5	4	0	0
Dysarthria
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Dyskinesia
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0
Hypoaesthesia
subjects affected / exposed	2 / 262 (0.76%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	3	1	0	0
Lethargy
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	2	0	0
Taste disorder
subjects affected / exposed	2 / 262 (0.76%)	7 / 307 (2.28%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	7	2	0	0
Amnesia
subjects affected / exposed	1 / 262 (0.38%)	5 / 307 (1.63%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	6	1	0	0
Aphasia
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Balance disorder
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	3	0	0
Burning feet syndrome
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Carotid artery dissection
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Disturbance in attention
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	1	2	0	1	0
Dizziness postural
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Extrapyramidal disorder
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Facial paralysis
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Loss of consciousness
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Muscle contractions involuntary
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Neuralgia
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	5	1	0	0
Notalgia paraesthetica
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Presyncope
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0
Restless legs syndrome
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Seizure
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Ageusia
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Anosmia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Burning sensation
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Carpal tunnel syndrome
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Cervical radiculopathy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	1	0	0
Cognitive disorder
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	2	1	0	1
Coordination abnormal
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Depressed level of consciousness
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Encephalopathy
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0
Haemorrhage intracranial
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Head discomfort
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Hemiparesis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Hypogeusia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Intracranial aneurysm
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Lumbar radiculopathy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Metabolic encephalopathy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Nerve compression
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Parosmia
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Peripheral motor neuropathy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Polyneuropathy
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Post herpetic neuralgia
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	2	0	0
Psychomotor hyperactivity
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Sciatica
subjects affected / exposed	0 / 262 (0.00%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	4	0	0	0
Sensory loss
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Sinus headache
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Spinal cord compression
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Trigeminal neuralgia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Vascular headache
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	48 / 262 (18.32%)	28 / 307 (9.12%)	42 / 130 (32.31%)	3 / 24 (12.50%)	3 / 12 (25.00%)
occurrences all number	88	70	113	4	7
Anaemia
subjects affected / exposed	33 / 262 (12.60%)	33 / 307 (10.75%)	30 / 130 (23.08%)	1 / 24 (4.17%)	2 / 12 (16.67%)
occurrences all number	46	59	71	2	6
Thrombocytopenia
subjects affected / exposed	9 / 262 (3.44%)	16 / 307 (5.21%)	17 / 130 (13.08%)	1 / 24 (4.17%)	4 / 12 (33.33%)
occurrences all number	24	39	39	1	5
Lymph node pain
subjects affected / exposed	6 / 262 (2.29%)	1 / 307 (0.33%)	0 / 130 (0.00%)	1 / 24 (4.17%)	1 / 12 (8.33%)
occurrences all number	6	1	0	1	1
Lymphopenia
subjects affected / exposed	4 / 262 (1.53%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	0	3	0	0
Leukopenia
subjects affected / exposed	3 / 262 (1.15%)	6 / 307 (1.95%)	9 / 130 (6.92%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	4	10	24	1	0
Febrile neutropenia
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	2	0	0
Lymphadenopathy
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	4 / 130 (3.08%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	2	1	4	1	0
Haemorrhagic diathesis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Normochromic anaemia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Blood loss anaemia
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	2	0	0
Bone marrow failure
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	1
Eosinophilia
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Iron deficiency anaemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	2 / 130 (1.54%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	1	2	0	1
Leukocytosis
subjects affected / exposed	0 / 262 (0.00%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	1	0	0
Lymphocytosis
subjects affected / exposed	0 / 262 (0.00%)	4 / 307 (1.30%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	8	0	0	0
Macrocytosis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Microcytic anaemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Pancytopenia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Paratracheal lymphadenopathy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Splenic infarction
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	7 / 262 (2.67%)	9 / 307 (2.93%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	10	2	0	0
Ear pain
subjects affected / exposed	6 / 262 (2.29%)	5 / 307 (1.63%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	5	1	0	0
Vertigo
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	1	1	0	0
Deafness
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	3	0	0	0
Ear congestion
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0
Ear pruritus
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Ear swelling
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
External ear inflammation
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Hypoacusis
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	3	1	0	0
Otorrhoea
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Vertigo positional
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Deafness unilateral
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Ear discomfort
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Ear disorder
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Excessive cerumen production
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Presbyacusis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Eye disorders
Vision blurred
subjects affected / exposed	14 / 262 (5.34%)	12 / 307 (3.91%)	4 / 130 (3.08%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	15	15	5	0	0
Dry eye
subjects affected / exposed	5 / 262 (1.91%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	6	0	0	0	1
Diplopia
subjects affected / exposed	3 / 262 (1.15%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0
Lacrimation increased
subjects affected / exposed	3 / 262 (1.15%)	5 / 307 (1.63%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	6	1	0	0
Eyelid ptosis
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	1	0	0	0
Vitreous floaters
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	1	0	0
Cataract
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	1	0	0
Conjunctival haemorrhage
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	1	0	0
Conjunctival hyperaemia
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Conjunctival oedema
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Erythema of eyelid
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Eye discharge
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Eye disorder
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Eye inflammation
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Eye pain
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	2	0	0
Eye pruritus
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Eyelid oedema
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Ocular discomfort
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Periorbital oedema
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	1	0	0
Retinal haemorrhage
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Visual acuity reduced
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0
Asthenopia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Blepharitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Conjunctivitis allergic
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Eye haemorrhage
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Eye irritation
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Eye swelling
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Glaucoma
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Hypermetropia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Mydriasis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Ocular hyperaemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Photopsia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Retinal detachment
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Retinal tear
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Scleral hyperaemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Visual impairment
subjects affected / exposed	0 / 262 (0.00%)	3 / 307 (0.98%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	4	0	0
Xerophthalmia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	114 / 262 (43.51%)	163 / 307 (53.09%)	62 / 130 (47.69%)	3 / 24 (12.50%)	7 / 12 (58.33%)
occurrences all number	252	372	96	5	16
Nausea
subjects affected / exposed	104 / 262 (39.69%)	120 / 307 (39.09%)	56 / 130 (43.08%)	2 / 24 (8.33%)	4 / 12 (33.33%)
occurrences all number	144	177	79	3	4
Vomiting
subjects affected / exposed	39 / 262 (14.89%)	65 / 307 (21.17%)	35 / 130 (26.92%)	1 / 24 (4.17%)	3 / 12 (25.00%)
occurrences all number	58	86	56	1	3
Constipation
subjects affected / exposed	30 / 262 (11.45%)	29 / 307 (9.45%)	19 / 130 (14.62%)	1 / 24 (4.17%)	1 / 12 (8.33%)
occurrences all number	32	37	21	1	1
Abdominal pain
subjects affected / exposed	28 / 262 (10.69%)	37 / 307 (12.05%)	17 / 130 (13.08%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	37	51	18	1	0
Gastrooesophageal reflux disease
subjects affected / exposed	17 / 262 (6.49%)	15 / 307 (4.89%)	4 / 130 (3.08%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	17	16	4	0	1
Dyspepsia
subjects affected / exposed	12 / 262 (4.58%)	26 / 307 (8.47%)	15 / 130 (11.54%)	2 / 24 (8.33%)	0 / 12 (0.00%)
occurrences all number	12	30	18	2	0
Abdominal pain upper
subjects affected / exposed	10 / 262 (3.82%)	18 / 307 (5.86%)	1 / 130 (0.77%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	11	30	1	1	0
Colitis
subjects affected / exposed	10 / 262 (3.82%)	5 / 307 (1.63%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	14	6	1	0	0
Abdominal distension
subjects affected / exposed	9 / 262 (3.44%)	20 / 307 (6.51%)	7 / 130 (5.38%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	10	21	8	1	0
Abdominal discomfort
subjects affected / exposed	8 / 262 (3.05%)	7 / 307 (2.28%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	9	7	3	0	0
Flatulence
subjects affected / exposed	8 / 262 (3.05%)	14 / 307 (4.56%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	9	15	3	0	0
Dry mouth
subjects affected / exposed	6 / 262 (2.29%)	5 / 307 (1.63%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	6	5	1	0	0
Dysphagia
subjects affected / exposed	6 / 262 (2.29%)	7 / 307 (2.28%)	5 / 130 (3.85%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	8	5	0	0
Stomatitis
subjects affected / exposed	6 / 262 (2.29%)	15 / 307 (4.89%)	7 / 130 (5.38%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	16	9	0	0
Anal incontinence
subjects affected / exposed	5 / 262 (1.91%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	2	0	0	0
Haemorrhoids
subjects affected / exposed	5 / 262 (1.91%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	5	2	2	0	1
Inguinal hernia
subjects affected / exposed	4 / 262 (1.53%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	2	0	0	0
Oral pain
subjects affected / exposed	4 / 262 (1.53%)	6 / 307 (1.95%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	7	2	0	0
Abdominal pain lower
subjects affected / exposed	3 / 262 (1.15%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	4	1	0	0
Ascites
subjects affected / exposed	3 / 262 (1.15%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	2	3	0	0
Gastritis
subjects affected / exposed	3 / 262 (1.15%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	3	0	0	0
Toothache
subjects affected / exposed	3 / 262 (1.15%)	4 / 307 (1.30%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	4	0	0	0
Eructation
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	0	0	0
Haemorrhoidal haemorrhage
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	2	0	0
Mouth ulceration
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	3	0	0
Proctalgia
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	1	0	0
Salivary hypersecretion
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Abdominal hernia
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Abdominal rigidity
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Anal polyp
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Barrett's oesophagus
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0
Chapped lips
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Diverticulum
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Duodenitis
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Enterocolitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0
Epigastric discomfort
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	3	0	0
Faeces discoloured
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Gastrointestinal pain
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	1	0	0
Gastrointestinal sounds abnormal
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Haematochezia
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	1	0	0
Hiatus hernia
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	3	0	0	0
Large intestine polyp
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Leukoplakia oral
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Lip blister
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Mouth haemorrhage
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Oesophagitis
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Oral dysaesthesia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Oral mucosal eruption
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Pancreatitis
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Parotid gland enlargement
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Proctitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Rectal haemorrhage
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Salivary gland pain
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Tongue coated
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Tongue disorder
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Umbilical hernia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Abdominal adhesions
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Abdominal mass
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Abdominal tenderness
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Abnormal faeces
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Aphthous ulcer
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Apical granuloma
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Autoimmune enteropathy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Breath odour
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Chronic gastritis
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	2	0	0	1
Colitis microscopic
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Defaecation urgency
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Diverticulum intestinal
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	0	0	0
Faecal vomiting
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Faeces soft
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	1
Frequent bowel movements
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Gastric disorder
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Gastric mucosa erythema
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Gastric ulcer
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Gastritis haemorrhagic
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Gastrooesophageal sphincter insufficiency
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Gingival bleeding
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	1	0	0	1
Gingival pain
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Haematemesis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Hypoaesthesia oral
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Ileus
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Impaired gastric emptying
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	1	0	0	1
Intra-abdominal haematoma
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Irritable bowel syndrome
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Large intestinal ulcer
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Lip exfoliation
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Melaena
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Mesenteric vein thrombosis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Neutropenic colitis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	4	0	0
Odynophagia
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Oedematous pancreatitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Oesophageal stenosis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Oral disorder
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Oral mucosal blistering
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Palatal disorder
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Pancreatitis acute
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Paraesthesia oral
subjects affected / exposed	0 / 262 (0.00%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	4	0	0	0
Periodontal disease
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Poor dental condition
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Reflux gastritis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Stomatitis necrotising
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Tongue ulceration
subjects affected / exposed	0 / 262 (0.00%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	4	0	0	0
Varices oesophageal
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	23 / 262 (8.78%)	27 / 307 (8.79%)	16 / 130 (12.31%)	3 / 24 (12.50%)	3 / 12 (25.00%)
occurrences all number	24	30	21	3	6
Pruritus
subjects affected / exposed	20 / 262 (7.63%)	14 / 307 (4.56%)	12 / 130 (9.23%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	24	19	16	1	0
Erythema
subjects affected / exposed	9 / 262 (3.44%)	8 / 307 (2.61%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	15	12	3	0	0
Alopecia
subjects affected / exposed	8 / 262 (3.05%)	10 / 307 (3.26%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	8	10	0	1	0
Hyperhidrosis
subjects affected / exposed	8 / 262 (3.05%)	13 / 307 (4.23%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	8	14	2	0	0
Night sweats
subjects affected / exposed	8 / 262 (3.05%)	22 / 307 (7.17%)	5 / 130 (3.85%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	9	25	5	1	0
Rash maculo-papular
subjects affected / exposed	8 / 262 (3.05%)	11 / 307 (3.58%)	9 / 130 (6.92%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	12	13	13	1	0
Dry skin
subjects affected / exposed	7 / 262 (2.67%)	10 / 307 (3.26%)	5 / 130 (3.85%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	8	11	6	0	0
Rash pruritic
subjects affected / exposed	4 / 262 (1.53%)	2 / 307 (0.65%)	4 / 130 (3.08%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	2	4	0	0
Skin mass
subjects affected / exposed	4 / 262 (1.53%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	3	0	0	0
Ecchymosis
subjects affected / exposed	3 / 262 (1.15%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	1	0	0
Skin ulcer
subjects affected / exposed	3 / 262 (1.15%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	3	2	0	0
Actinic keratosis
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	1	0	0
Dermatitis
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0
Pain of skin
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	1	0	0
Urticaria
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	3	4	0	1	0
Angioedema
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Blister
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Decubitus ulcer
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Dermatitis atopic
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Eczema asteatotic
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Exfoliative rash
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Hyperkeratosis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Hypersensitivity vasculitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Onychoclasis
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Psoriasis
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	1	8	0	1	0
Purpura
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Rash macular
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Rosacea
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Skin burning sensation
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Skin discolouration
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	2	0	0
Skin fissures
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Skin irritation
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	0	0
Skin lesion
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	2	0	0
Skin tightness
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Stasis dermatitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Cold sweat
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Dermal cyst
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Dermatitis acneiform
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Dermatitis bullous
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Dermatitis exfoliative generalised
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	0	0	0
Drug eruption
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Eczema
subjects affected / exposed	0 / 262 (0.00%)	4 / 307 (1.30%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	7	0	0	0
Erythema multiforme
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Nail discolouration
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Papule
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Photosensitivity reaction
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Purpura senile
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Rash erythematous
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Scab
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Scar pain
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Skin atrophy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Skin discomfort
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Skin exfoliation
subjects affected / exposed	0 / 262 (0.00%)	4 / 307 (1.30%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	6	0	0	0
Skin hypopigmentation
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Skin necrosis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Skin plaque
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Skin reaction
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Telangiectasia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Renal and urinary disorders
Pollakiuria
subjects affected / exposed	5 / 262 (1.91%)	5 / 307 (1.63%)	4 / 130 (3.08%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	5	4	0	0
Acute kidney injury
subjects affected / exposed	4 / 262 (1.53%)	3 / 307 (0.98%)	7 / 130 (5.38%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	6	3	9	0	0
Haematuria
subjects affected / exposed	4 / 262 (1.53%)	3 / 307 (0.98%)	1 / 130 (0.77%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	5	3	1	0	1
Dysuria
subjects affected / exposed	3 / 262 (1.15%)	0 / 307 (0.00%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	2	0	0
Chronic kidney disease
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	3	1	0	0
Proteinuria
subjects affected / exposed	2 / 262 (0.76%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	3	0	0	0
Calculus urinary
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Micturition urgency
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	1	0	0
Polyuria
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	0	0	0
Renal failure
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Strangury
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Ureteric stenosis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Urinary hesitation
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Urinary retention
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	2	0	0
Urinary tract obstruction
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Urine odour abnormal
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Azotaemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Bladder discomfort
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Haemorrhage urinary tract
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Hydronephrosis
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Hypertonic bladder
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Nephrolithiasis
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	1	0	0
Nephropathy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	0	0	0
Nocturia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Renal pain
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Ureterolithiasis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Urinary incontinence
subjects affected / exposed	0 / 262 (0.00%)	4 / 307 (1.30%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	5	1	0	0
Urinary tract pain
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Adrenal insufficiency
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Hyperparathyroidism
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Hypercalcaemia of malignancy
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Hyperthyroidism
subjects affected / exposed	0 / 262 (0.00%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	0	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	32 / 262 (12.21%)	32 / 307 (10.42%)	11 / 130 (8.46%)	4 / 24 (16.67%)	1 / 12 (8.33%)
occurrences all number	42	42	14	6	1
Arthralgia
subjects affected / exposed	21 / 262 (8.02%)	34 / 307 (11.07%)	17 / 130 (13.08%)	3 / 24 (12.50%)	0 / 12 (0.00%)
occurrences all number	48	47	18	3	0
Pain in extremity
subjects affected / exposed	12 / 262 (4.58%)	25 / 307 (8.14%)	9 / 130 (6.92%)	3 / 24 (12.50%)	1 / 12 (8.33%)
occurrences all number	12	32	10	4	1
Muscle spasms
subjects affected / exposed	9 / 262 (3.44%)	19 / 307 (6.19%)	8 / 130 (6.15%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	14	23	8	1	0
Muscular weakness
subjects affected / exposed	8 / 262 (3.05%)	16 / 307 (5.21%)	8 / 130 (6.15%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	8	20	9	1	0
Flank pain
subjects affected / exposed	6 / 262 (2.29%)	11 / 307 (3.58%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	8	12	2	0	0
Groin pain
subjects affected / exposed	5 / 262 (1.91%)	10 / 307 (3.26%)	3 / 130 (2.31%)	2 / 24 (8.33%)	1 / 12 (8.33%)
occurrences all number	5	10	3	2	1
Musculoskeletal pain
subjects affected / exposed	5 / 262 (1.91%)	13 / 307 (4.23%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	19	4	0	0
Joint swelling
subjects affected / exposed	4 / 262 (1.53%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	2	0	0	0
Bone pain
subjects affected / exposed	3 / 262 (1.15%)	4 / 307 (1.30%)	8 / 130 (6.15%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	4	7	8	1	0
Musculoskeletal discomfort
subjects affected / exposed	3 / 262 (1.15%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	1	0	0	0
Arthritis
subjects affected / exposed	2 / 262 (0.76%)	3 / 307 (0.98%)	1 / 130 (0.77%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	2	4	1	1	0
Muscle tightness
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	2 / 262 (0.76%)	4 / 307 (1.30%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	5	2	0	0
Osteoporosis
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Pain in jaw
subjects affected / exposed	2 / 262 (0.76%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	3	0	0	0
Axillary mass
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Intervertebral disc protrusion
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Joint stiffness
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	1	0	0	0	1
Osteoarthritis
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	1	0	0
Periarthritis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Psoriatic arthropathy
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Rheumatoid arthritis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Rotator cuff syndrome
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Spinal osteoarthritis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Spinal pain
subjects affected / exposed	1 / 262 (0.38%)	6 / 307 (1.95%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	12	0	0	0
Trigger finger
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Bursitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Coccydynia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Gouty arthritis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Joint range of motion decreased
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Limb discomfort
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Muscle fatigue
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Muscle twitching
subjects affected / exposed	0 / 262 (0.00%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	0	0	0
Musculoskeletal stiffness
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Rhabdomyolysis
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Synovial cyst
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Tendon pain
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Tendonitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Infections and infestations
Urinary tract infection
subjects affected / exposed	17 / 262 (6.49%)	22 / 307 (7.17%)	11 / 130 (8.46%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	24	27	14	1	0
Pneumonia
subjects affected / exposed	12 / 262 (4.58%)	10 / 307 (3.26%)	5 / 130 (3.85%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	19	11	5	0	0
Upper respiratory tract infection
subjects affected / exposed	12 / 262 (4.58%)	42 / 307 (13.68%)	7 / 130 (5.38%)	4 / 24 (16.67%)	1 / 12 (8.33%)
occurrences all number	15	49	10	4	1
COVID-19
subjects affected / exposed	8 / 262 (3.05%)	9 / 307 (2.93%)	1 / 130 (0.77%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	8	11	1	1	0
Sinusitis
subjects affected / exposed	8 / 262 (3.05%)	8 / 307 (2.61%)	4 / 130 (3.08%)	2 / 24 (8.33%)	2 / 12 (16.67%)
occurrences all number	8	13	5	2	3
Oral candidiasis
subjects affected / exposed	7 / 262 (2.67%)	2 / 307 (0.65%)	5 / 130 (3.85%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	10	2	5	0	0
Bronchitis
subjects affected / exposed	5 / 262 (1.91%)	5 / 307 (1.63%)	5 / 130 (3.85%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	6	7	10	1	0
Candida infection
subjects affected / exposed	5 / 262 (1.91%)	4 / 307 (1.30%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	4	1	0	0
Nasopharyngitis
subjects affected / exposed	5 / 262 (1.91%)	7 / 307 (2.28%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	11	2	0	0
Respiratory tract infection
subjects affected / exposed	5 / 262 (1.91%)	5 / 307 (1.63%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	8	5	0	0	0
Cytomegalovirus infection reactivation
subjects affected / exposed	4 / 262 (1.53%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	8	0	2	0	0
Cytomegalovirus infection
subjects affected / exposed	3 / 262 (1.15%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	1	0	0
Folliculitis
subjects affected / exposed	3 / 262 (1.15%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	0	0	0	0
Gastroenteritis
subjects affected / exposed	3 / 262 (1.15%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	3	0	0	0
Influenza
subjects affected / exposed	3 / 262 (1.15%)	5 / 307 (1.63%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	7	1	0	0
Lower respiratory tract infection
subjects affected / exposed	3 / 262 (1.15%)	8 / 307 (2.61%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	9	0	0	0
Rhinitis
subjects affected / exposed	3 / 262 (1.15%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	7	3	0	0	0
Sepsis
subjects affected / exposed	3 / 262 (1.15%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	1	0	0
Cellulitis
subjects affected / exposed	2 / 262 (0.76%)	4 / 307 (1.30%)	2 / 130 (1.54%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	2	7	3	0	1
Chronic sinusitis
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0
Conjunctivitis
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	1	0	0
Cystitis
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	1	1	0	0
Diverticulitis
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	1 / 130 (0.77%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	3	0	1	1	0
Escherichia infection
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Herpes zoster
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	1	0	0
Oral herpes
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	2	1	0	0
Oral infection
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Pharyngitis
subjects affected / exposed	2 / 262 (0.76%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	2	0	0	0
Skin infection
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	2	1	0	1	0
Acute sinusitis
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	2	1	0	0
Asymptomatic bacteriuria
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Bacteraemia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0
Bronchiolitis
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Cellulitis of male external genital organ
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Clostridium difficile colitis
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	3	4	0	0
Clostridium difficile infection
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	1	0	0
Cytomegalovirus viraemia
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Ear infection
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Enterocolitis infectious
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Epididymitis
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Fungal infection
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Gastric infection
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Hordeolum
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Gastrointestinal infection
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Infection
subjects affected / exposed	1 / 262 (0.38%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	3	0	0	0
Latent tuberculosis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Molluscum contagiosum
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Nail infection
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Nasal herpes
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Oesophageal candidiasis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	1	0	1	0	1
Post procedural infection
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Proctitis herpes
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Pulpitis dental
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Scrotal infection
subjects affected / exposed ^[20]	1 / 157 (0.64%)	0 / 168 (0.00%)	0 / 78 (0.00%)	0 / 16 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0
Sialoadenitis
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0	0	0
Tinea cruris
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Tooth infection
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	4	0	0	0
Vaginal infection
subjects affected / exposed ^[21]	1 / 105 (0.95%)	1 / 139 (0.72%)	0 / 52 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)
occurrences all number	1	1	0	1	0
Viral infection
subjects affected / exposed	1 / 262 (0.38%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	3	0	0	0
Alpha haemolytic streptococcal infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
COVID-19 pneumonia
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	0	0	0
Campylobacter infection
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Enterocolitis viral
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Erysipelas
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Eye infection
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Fungal skin infection
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	2	0	0
Gastroenteritis norovirus
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	1	0	0
Gastrointestinal viral infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Gingivitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Helicobacter gastritis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Helicobacter infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Herpes simplex
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Herpes virus infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Infected cyst
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Kidney infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Localised infection
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Measles
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Moraxella infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Neutropenic sepsis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Onychomycosis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Ophthalmic herpes simplex
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Oral fungal infection
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Periorbital cellulitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Pneumonia haemophilus
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Pulmonary mycosis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Septic shock
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Skin bacterial infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Splenic infection
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Staphylococcal sepsis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Streptococcal bacteraemia
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Tinea pedis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Tinea versicolour
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Urinary tract infection enterococcal
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Viral pharyngitis
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 262 (0.00%)	4 / 307 (1.30%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	4	1	0	0
Vulvovaginal mycotic infection
subjects affected / exposed ^[22]	0 / 105 (0.00%)	0 / 139 (0.00%)	1 / 52 (1.92%)	0 / 8 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Wound infection
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Contusion
subjects affected / exposed	10 / 262 (3.82%)	10 / 307 (3.26%)	5 / 130 (3.85%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	15	11	6	0	0
Ligament sprain
subjects affected / exposed	4 / 262 (1.53%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	4	2	0	0	0
Humerus fracture
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	2	0	0	0	1
Metabolism and nutrition disorders
Hypokalaemia
subjects affected / exposed	38 / 262 (14.50%)	37 / 307 (12.05%)	25 / 130 (19.23%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	57	62	38	0	0
Decreased appetite
subjects affected / exposed	37 / 262 (14.12%)	59 / 307 (19.22%)	32 / 130 (24.62%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	45	83	35	1	0
Hypomagnesaemia
subjects affected / exposed	22 / 262 (8.40%)	20 / 307 (6.51%)	15 / 130 (11.54%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	31	26	22	1	0
Dehydration
subjects affected / exposed	11 / 262 (4.20%)	18 / 307 (5.86%)	16 / 130 (12.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	13	20	20	0	0
Hypophosphataemia
subjects affected / exposed	11 / 262 (4.20%)	12 / 307 (3.91%)	6 / 130 (4.62%)	0 / 24 (0.00%)	1 / 12 (8.33%)
occurrences all number	13	22	15	0	2
Hyponatraemia
subjects affected / exposed	8 / 262 (3.05%)	6 / 307 (1.95%)	7 / 130 (5.38%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	10	10	11	0	0
Hypercalcaemia
subjects affected / exposed	5 / 262 (1.91%)	7 / 307 (2.28%)	3 / 130 (2.31%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	5	10	3	0	0
Hyperglycaemia
subjects affected / exposed	5 / 262 (1.91%)	8 / 307 (2.61%)	4 / 130 (3.08%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	5	10	6	1	0
Hyperuricaemia
subjects affected / exposed	5 / 262 (1.91%)	11 / 307 (3.58%)	7 / 130 (5.38%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	6	14	7	2	0
Hypocalcaemia
subjects affected / exposed	4 / 262 (1.53%)	11 / 307 (3.58%)	5 / 130 (3.85%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	6	18	5	0	0
Hypercholesterolaemia
subjects affected / exposed	3 / 262 (1.15%)	4 / 307 (1.30%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	8	2	0	0
Hyperkalaemia
subjects affected / exposed	3 / 262 (1.15%)	9 / 307 (2.93%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	10	0	0	0
Tumour lysis syndrome
subjects affected / exposed	3 / 262 (1.15%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0	0	0
Vitamin D deficiency
subjects affected / exposed	3 / 262 (1.15%)	5 / 307 (1.63%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	5	0	0	0
Gout
subjects affected / exposed	2 / 262 (0.76%)	5 / 307 (1.63%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	5	1	0	0
Hyperlipidaemia
subjects affected / exposed	2 / 262 (0.76%)	0 / 307 (0.00%)	0 / 130 (0.00%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	2	0	0	1	0
Hypertriglyceridaemia
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0
Hypoalbuminaemia
subjects affected / exposed	2 / 262 (0.76%)	5 / 307 (1.63%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	5	4	0	0
Hypoglycaemia
subjects affected / exposed	2 / 262 (0.76%)	5 / 307 (1.63%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	5	0	0	0
Increased appetite
subjects affected / exposed	2 / 262 (0.76%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	1	0	0	0
Acidosis
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	1	0	0
Diabetes mellitus
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0
Fluid overload
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Fluid retention
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	1	0	0
Iron deficiency
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	1	0	0
Magnesium deficiency
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Malnutrition
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	2 / 130 (1.54%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	2	0	0
Metabolic acidosis
subjects affected / exposed	1 / 262 (0.38%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	1	0	0	0
Type 2 diabetes mellitus
subjects affected / exposed	1 / 262 (0.38%)	0 / 307 (0.00%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0
Abnormal loss of weight
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Cachexia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Failure to thrive
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Hypermagnesaemia
subjects affected / exposed	0 / 262 (0.00%)	2 / 307 (0.65%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0
Hypernatraemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Hyperphosphataemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	1	0	0
Hypochloraemia
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Hypoproteinaemia
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Obesity
subjects affected / exposed	0 / 262 (0.00%)	0 / 307 (0.00%)	1 / 130 (0.77%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0
Vitamin B12 deficiency
subjects affected / exposed	0 / 262 (0.00%)	3 / 307 (0.98%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	3	0	0	0
Zinc deficiency
subjects affected / exposed	0 / 262 (0.00%)	1 / 307 (0.33%)	0 / 130 (0.00%)	0 / 24 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0
Myalgia
subjects affected / exposed	14 / 262 (5.34%)	24 / 307 (7.82%)	4 / 130 (3.08%)	2 / 24 (8.33%)	1 / 12 (8.33%)
occurrences all number	15	29	6	3	1
Neck pain
subjects affected / exposed	12 / 262 (4.58%)	5 / 307 (1.63%)	5 / 130 (3.85%)	1 / 24 (4.17%)	0 / 12 (0.00%)
occurrences all number	13	5	5	1	0

Notes
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the male population in this study.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the male population in this study.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the male population in this study.
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the male population in this study.
[14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the male population in this study.
[15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the male population in this study.
[16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the male population in this study.
[17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.
[18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.
[19] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.
[20] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the male population in this study.
[21] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.
[22] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Number of subjects exposed to this adverse event term is based on the female population in this study.

More information

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Were there any global substantial amendments to the protocol? Yes

25 Aug 2016

All subjects are now required to start prophylaxis treatment with pneumocystis jiroveci pneumonia (PCP) and antiviral therapy within 7 days prior to randomisation, whereas this was previously at investigator discretion. The phrasing of response assessment intervals has been revised for clarity from “on weeks 8,16, and 24, and then every 12 weeks thereafter,” to “at the end of Cycles 2, 4, and 6, and then every 3 cycles thereafter”. The shelf life of ublituximab has been increased to 36 months from 24 months when stored between +2 ͦC / +8 ͦC to reflect newly available stability data on ublituximab drug product. The tissue sample requirements at screening were revised for subjects with previous documentation of DLBCL subtype. For these subjects, tissue can now be submitted within +/-30 days of Day 1 of Cycle 1. If no documentation of DLBCL subtype is available prior to screening, a tissue sample must be submitted during the screening period to allow for central determination of DLBCL subtype prior to randomisation. Updated to include the most recent AE information related to ublituximab and TGR-1202 corresponding to the latest Investigator’s Brochures.

15 Jan 2017

Women of childbearing potential were required to undergo monthly urine pregnancy testing beginning in Cycle 2.

12 Apr 2017

Additional cohorts were added, and eligibility criteria were expanded to allow enrolment of subjects with the following indolent types of NHL: FL, SLL, and MZL. Arm C was added to evaluate the combination of TGR-1202, ublituximab, and bendamustine in subjects with DLBCL and those with FL or SLL.Stratification by DLBCL subtype prior to randomisation was removed, however archived tissue for central determination of DLBCL subtype is still required within 30 days of Day 1 of Cycle 1. Number of subjects was expanded- up to approximately 400 subjects with DLBCL, up to approximately 400 subjects with FL or SLL, and up to approximately 60 subjects with MZL, provided no arms are closed for futility or at planned interim analyses. The number of potential study centres was expanded from up to 100 to up to 150, and the timeframe for enrolment was expanded from up to 14 months to up to 36 months. The window for use of medically acceptable methods of contraception for female subjects of child-bearing potential and male partners was expanded from throughout the study period and for 30 days after the last dose of either study drug to throughout the study period and for 4 months after the last dose of either study drug. Exclusion criteria 1, 3, 4,5, and 9 were updated. The response assessment schedule was revised from at the end of Cycles 2, 4, and 6 and then every 3 cycles thereafter, to during Cycles 3 and 6, and then every 3 cycles thereafter. The window for tumour evaluations was expanded from +/- 7 days to +/- 14 days. The screening period was expanded from 21 days to 28 days. Unilateral bone marrow aspirate and/or biopsy was only needed postbaseline to confirm a CR in subjects with marrow involvement at baseline and without FDG-avid disease. PET scans were previously required at baseline and routinely in subjects with FDG-avid disease. Study Assessment Table was amended and a second assessment table for subjects on the ublituximab+TGR-1202+bendamustine regimen added.

01 Oct 2017

Provided additional justification for the study of TGR-1202 monotherapy in subjects with MZL. Inclusion criterion 1(d), 2(a), 4(d) and exclusion criterion 9(c) were modified. The FL/SLL cohort was modified to include a Stage 1 to evaluate TGR-1202 monotherapy in up to 150 subjects prior to proceeding to Stage 2 which will randomise subjects to either TGR-1202 alone or in combination with ublituximab. The schedule for response evaluation previously stated to evaluate response “during” Cycles 3 and 6 and then every 3 cycles thereafter and was clarified to evaluate response “at the end of Cycle 3 and then within 14 days prior to Cycle 6, Day 1, and every 3 cycles thereafter (9, 12, etc.)”. The study assessment tables were updated to specify that bone marrow aspirate and/or biopsy was optional only for subjects with DLBCL and required for subjects with FL, SLL, and MZL. Updated to include sparse sampling for population pharmacokinetics from all enrolled subjects, not just subjects in the DLBCL cohort, and the sparse sampling instructions were clarified. Updated to include information regarding a new vial size for ublituximab. Updated to clarify that pre-medications for bendamustine are recommended but optional and per institutional standard of care, which should at least include use of a corticosteroid, and that use of prophylactic growth factor support is allowed. Provided more specific instructions around dose-modifications in the event of diarrhoea and/or colitis. Reference to an interim analysis in the FL/SLL cohort was removed. Futility-stopping rules were added for the MZL cohort and the FL/SLL cohort based on Simon’s 2-stage design.

15 Feb 2018

The number of trial sites was expanded from 150 to 200 sites. A cohort of subjects with MCL was added to the study, affecting the following sections: Primary objectives: amended to include efficacy objectives for MCL subjects; inclusion criteria 1, 2 and exclusion criteria 7, 8 were amended. Enrolment to Arm A of the DLBCL Cohort was suspended following accrual of a sufficient number of subjects. The schedule for response evaluation previously stated to evaluate response “at the end of Cycle 3 and then within 14 days prior to Cycle 6, Day 1, and every 3 cycles thereafter (9, 12, etc.)” and was amended to evaluated response, “at the end of Cycle 3 and then within 14 days prior to day 1 of Cycles 6, 9, and 12. After Cycle 12, response assessments should occur every 6 cycles or more frequently.”. Amended to include background information and rationale for the addition of MCL subjects to this study. Modified to provide dose delay and/or modification guidelines for bendamustine for subjects experiencing occurrence of neutropenic fever or infection. The risk profile of ublituximab and TGR-1202 was updated to reflect the most recent safety data available from each agent. Other minor clarifications and administrative updates were made.

20 Aug 2018

The primary objectives of the study were re-written to reflect ORR as the primary endpoint for all cohorts. The key secondary objectives of CR rate for subjects with FL or SLL and PFS for subjects with DLBCL were revised to be Secondary Objectives. Inclusion Criterion 2 was amended. Stage 2 of the FL and SLL cohort was revised as follows: Stage 2 will only enrol subjects with FL, and no longer will enrol SLL, subjects will be randomised in a 3:1:1 ratio to receive ublituximab + TGR-1202 (Arm A), TGR-1202 monotherapy (Arm B), or ublituximab monotherapy (Arm D), subjects randomised to Arm D with documented progression will be eligible to cross-over to receive TGR-1202 monotherapy. Stage 2 of the MZL cohort was added to enrol an additional 60 subjects to receive the combination of ublituximab + TGR-1202. The duration of ublituximab therapy was truncated to stop at the end of Cycle 24 for any ublituximab-containing arm. Guidelines for holding anti-hypertensive medications during ublituximab infusions were updated. Eligibility for subjects with DLBCL was removed based on completion of target enrolment in the DLBCL cohorts. Statistical assumptions for the MZL, FL/SLL, and DLBCL cohorts were revised in accordance with recent Statistical Analysis Plans. Updated to provide further information on preferred PCP prophylactic agents. Updated to include the most recent AE information related to ublituximab and TGR-1202 corresponding to the latest Investigator’s Brochures. Minor administrative updates and typographical errors were corrected throughout.

20 Sep 2018

Inclusion Criterion 2C for subjects with MCL was clarified to state that the prior BTK inhibitor requirement is limited to only ibrutinib or acalabrutinib. Exclusion Criterion 1 was updated to allow palliative radiation therapy during the 21-day period prior to Day 1 of Cycle 1. Updated to include cytomegalovirus (CMV) surveillance for all subjects. Amended to provide additional guidance for ublituximab pre-medications. Revised to allow dose delays of any study medication for durations longer than 28 days to recover from toxicity. All dose modifications should now be reported in the Interactive Web Response System (IWRS), with questions regarding dose modifications referred to TG Therapeutics. Updated to provide clarification on the liver toxicity dose modification guidelines. Updated to include a cut-off date for the safety information for ublituximab and umbralisib. The latest safety information for each study drug is contained in the most recent investigator’s brochures. Administrative updates and typographical errors were corrected throughout, including the changing of terminology from “patient” to “subject” and the inclusion of the generic name for “umbralisib” for TGR-1202.

19 Nov 2020

Cover page updated to add medical monitor and update study chair information. Eligibility criteria inclusion 1 updated to note that DLBCL is no longer enrolling, however subjects with SLL are eligible for enrolment. Eligibility criteria inclusion 2 updated to include FL, SLL, and MZL subjects that are treatment naïve or previously treated are now eligible. FL subjects are no longer required to be relapsed or refractory after ≥ 2 prior lines of systemic therapy, nor does the requirement to have received an anti-CD20 monoclonal antibody (mAb) and an alkylating agent apply. MZL subjects are no longer required to have prior treatment with one or more lines of prior treatment including at least one CD20-directed regimen (either as monotherapy or as chemoimmunotherapy) with documented failure to achieve at least PR or documented PD after the most recent systemic treatment regimen. Exclusion criteria 3 updated to clarify evidence of chronic active HBV is a detectable hepatitis b surface antigen. Updated to include a Stage 3 to include new dosing cohorts for subjects with FL, SLL or MZL. Ublituximab 36 milliliter per 900 mg vials are now available, protocol updated throughout to reflect the updated vials size, stability information, and dilution instructions. The storage of ublituximab if diluted in polyolefin (PO) infusion bags and lines can be extended to 48 hours refrigerated. Stage 3 enrolment and sample size added. Sparse Sampling PK added for subjects enrolled to Stage 3. Added to clarify umbralisib dosing cohorts in Stage 3. Updated to add details on crossover from Arm D to Arm B. Information on scheduling of ublituximab pre-medications for potential infusion related reactions (IRR) updated to be more clear, information on prophylaxis with antiviral agents for hepatitis B added for subjects with a prior history of hepatitis B and for those with a positive anti-HBc with negative HBsAg at screening. Updated contact information for any product quality complaint.

Were there any global interruptions to the trial? No

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

Sponsor opted to terminate the study due to business decision.

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