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Clinical Trial Results:
A Phase 1/2a Dose Escalation and Cohort Expansion Study for Safety, Tolerability, and Efficacy of BMS-986156 Administered Alone and in Combination with Nivolumab (BMS-936558, anti PD-1 Monoclonal Antibody) in Advanced Solid Tumors

Summary
EudraCT number	2015-002505-11
Trial protocol	NL BE ES DE FR IT
Global end of trial date	28 Aug 2019

Results information
Results version number	v1(current)
This version publication date	05 Jan 2023
First version publication date	05 Jan 2023
Other versions
Summary report(s)	Delayed Results Explanation

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

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Trial information

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Sponsor protocol code

CA009-002

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Bristol-Myers Squibb

Sponsor organisation address

Chaussée de la Hulpe 185, Brussels, Belgium, 1170

Public contact

Bristol-Myers Squibb International Corporation, EU Study Start-Up Unit, Clinical.Trials@bms.com

Scientific contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

28 Aug 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Aug 2019

Was the trial ended prematurely?

Main objective of the trial

The primary objective is to determine the safety, tolerability, dose-limiting toxicities (DLTs), and MTD/MAD/alternate dose(s) of BMS-986156 administered alone and in combination with nivolumab in subjects with advanced solid tumors.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

09 Oct 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 4

Country: Number of subjects enrolled

Australia: 61

Country: Number of subjects enrolled

Canada: 35

Country: Number of subjects enrolled

France: 30

Country: Number of subjects enrolled

Germany: 7

Country: Number of subjects enrolled

Italy: 22

Country: Number of subjects enrolled

Netherlands: 38

Country: Number of subjects enrolled

Spain: 25

Country: Number of subjects enrolled

Switzerland: 28

Country: Number of subjects enrolled

United States: 28

Country: Number of subjects enrolled

Belgium: 14

Worldwide total number of subjects

292

EEA total number of subjects

140

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

196

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

292 subjects randomized and treated

Period 1 title

Treatment Period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part A: BMS-986156 10mg

Arm description

BMS-986156 10mg Q2W

Arm type

Experimental

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Part A: BMS-986156 30mg

Arm description

BMS-986156 30mg Q2W

Arm type

Experimental

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Part A: BMS-986156 100mg

Arm description

BMS-986156 100mg Q2W

Arm type

Experimental

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Part A: BMS-986156 240mg

Arm description

BMS-986156 240mg Q2W

Arm type

Experimental

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Part A: BMS-986156 800mg

Arm description

BMS-986156 800mg Q2W

Arm type

Experimental

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Part C: BMS-986156 240mg

Arm description

BMS-986156 240mg Q2W

Arm type

Experimental

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Part C: BMS-986156 800mg

Arm description

BMS-986156 800mg Q2W

Arm type

Experimental

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Part B: BMS-986156 30mg + Nivo 240mg

Arm description

BMS986156 30mg Q2W + Nivo 240mg Q2W

Arm type

Experimental

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Investigational medicinal product name

nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Part B: BMS-986156 100mg + Nivo 240mg

Arm description

BMS986156 100mg Q2W + Nivo 240mg Q2W

Arm type

Experimental

Investigational medicinal product name

nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Part B: BMS-986156 240mg + Nivo 240mg

Arm description

BMS986156 240mg Q2W + Nivo 240mg Q2W

Arm type

Experimental

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Investigational medicinal product name

nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Part B: BMS-986156 800mg + Nivo 240mg

Arm description

BMS986156 800mg Q2W + Nivo 240mg Q2W

Arm type

Experimental

Investigational medicinal product name

nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Part D: BMS-986156 240mg + Nivo 240mg

Arm description

BMS986156 240mg Q2W + Nivo 240mg Q2W

Arm type

Experimental

Investigational medicinal product name

nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Part E: BMS-986156 480mg + Nivo 480mg

Arm description

BMS986156 480mg Q4W + Nivo 480mg Q4W

Arm type

Experimental

Investigational medicinal product name

nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Investigational medicinal product name

BMS-986156

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

100mg/vial (10mg/mL)

Number of subjects in period 1	Part A: BMS-986156 10mg	Part A: BMS-986156 30mg	Part A: BMS-986156 100mg	Part A: BMS-986156 240mg	Part A: BMS-986156 800mg	Part C: BMS-986156 240mg	Part C: BMS-986156 800mg	Part B: BMS-986156 30mg + Nivo 240mg	Part B: BMS-986156 100mg + Nivo 240mg	Part B: BMS-986156 240mg + Nivo 240mg	Part B: BMS-986156 800mg + Nivo 240mg	Part D: BMS-986156 240mg + Nivo 240mg	Part E: BMS-986156 480mg + Nivo 480mg
Started	4	6	4	6	9	3	2	3	9	14	11	188	33
Completed	0	0	0	0	0	1	0	0	2	3	3	23	7
Not completed	4	6	4	6	9	2	2	3	7	11	8	165	26
Adverse Event unrelated to study drug	-	1	-	-	-	-	-	-	-	1	-	11	2
Study drug toxicity	-	-	-	-	-	-	-	-	-	1	-	3	-
Other Reasons	-	-	-	-	-	-	-	-	-	-	-	-	1
No longer meets study criteria	-	-	-	-	-	-	-	-	-	-	-	1	-
Disease Progression	4	4	4	6	8	2	2	3	7	9	7	143	23
participant request to discontinue	-	1	-	-	1	-	-	-	-	-	1	4	-
participant withdrew consent	-	-	-	-	-	-	-	-	-	-	-	3	-

Baseline characteristics

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Reporting group title

Part A: BMS-986156 10mg

Reporting group description

BMS-986156 10mg Q2W

Reporting group title

Part A: BMS-986156 30mg

Reporting group description

BMS-986156 30mg Q2W

Reporting group title

Part A: BMS-986156 100mg

Reporting group description

BMS-986156 100mg Q2W

Reporting group title

Part A: BMS-986156 240mg

Reporting group description

BMS-986156 240mg Q2W

Reporting group title

Part A: BMS-986156 800mg

Reporting group description

BMS-986156 800mg Q2W

Reporting group title

Part C: BMS-986156 240mg

Reporting group description

BMS-986156 240mg Q2W

Reporting group title

Part C: BMS-986156 800mg

Reporting group description

BMS-986156 800mg Q2W

Reporting group title

Part B: BMS-986156 30mg + Nivo 240mg

Reporting group description

BMS986156 30mg Q2W + Nivo 240mg Q2W

Reporting group title

Part B: BMS-986156 100mg + Nivo 240mg

Reporting group description

BMS986156 100mg Q2W + Nivo 240mg Q2W

Reporting group title

Part B: BMS-986156 240mg + Nivo 240mg

Reporting group description

BMS986156 240mg Q2W + Nivo 240mg Q2W

Reporting group title

Part B: BMS-986156 800mg + Nivo 240mg

Reporting group description

BMS986156 800mg Q2W + Nivo 240mg Q2W

Reporting group title

Part D: BMS-986156 240mg + Nivo 240mg

Reporting group description

BMS986156 240mg Q2W + Nivo 240mg Q2W

Reporting group title

Part E: BMS-986156 480mg + Nivo 480mg

Reporting group description

BMS986156 480mg Q4W + Nivo 480mg Q4W

Reporting group values	Part A: BMS-986156 10mg	Part A: BMS-986156 30mg	Part A: BMS-986156 100mg	Part A: BMS-986156 240mg	Part A: BMS-986156 800mg	Part C: BMS-986156 240mg	Part C: BMS-986156 800mg	Part B: BMS-986156 30mg + Nivo 240mg	Part B: BMS-986156 100mg + Nivo 240mg	Part B: BMS-986156 240mg + Nivo 240mg	Part B: BMS-986156 800mg + Nivo 240mg	Part D: BMS-986156 240mg + Nivo 240mg	Part E: BMS-986156 480mg + Nivo 480mg	Total
Number of subjects	4	6	4	6	9	3	2	3	9	14	11	188	33	292
Age categorical
Units: Subjects
Adults (18-64 years)	2	5	3	5	7	2	1	3	6	9	9	124	19	195
From 65-84 years	2	1	1	1	2	1	1	0	3	4	2	64	14	96
85 years and over	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Age Continuous
Units: Years
arithmetic mean (standard deviation)	55.3 ± 18.57	59.7 ± 5.82	57.4 ± 10.08	49.5 ± 13.28	51.0 ± 13.82	58.3 ± 19.43	56.5 ± 9.19	50.7 ± 20.50	57.2 ± 12.09	55.6 ± 18.67	57.0 ± 9.30	59.0 ± 11.58	57.2 ± 13.05	-
Sex: Female, Male
Units: Participants
Female	4	1	1	3	5	1	1	2	4	5	7	100	22	156
Male	0	5	3	3	4	2	1	1	5	9	4	88	11	136
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Asian	0	0	1	1	1	0	0	0	1	2	0	13	5	24
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Black or African American	1	0	0	0	0	0	0	0	0	0	0	2	0	3
White	3	6	3	5	8	3	2	3	8	12	11	171	27	262
More than one race	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0	2	1	3
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	0	2	0	0	0	0	0	0	0	0	1	1	4
Not Hispanic or Latino	4	6	1	3	5	1	0	2	6	7	4	51	11	101
Unknown or Not Reported	0	0	1	3	4	2	2	1	3	7	7	136	21	187

End points

Top of page

Reporting group title

Part A: BMS-986156 10mg

Reporting group description

BMS-986156 10mg Q2W

Reporting group title

Part A: BMS-986156 30mg

Reporting group description

BMS-986156 30mg Q2W

Reporting group title

Part A: BMS-986156 100mg

Reporting group description

BMS-986156 100mg Q2W

Reporting group title

Part A: BMS-986156 240mg

Reporting group description

BMS-986156 240mg Q2W

Reporting group title

Part A: BMS-986156 800mg

Reporting group description

BMS-986156 800mg Q2W

Reporting group title

Part C: BMS-986156 240mg

Reporting group description

BMS-986156 240mg Q2W

Reporting group title

Part C: BMS-986156 800mg

Reporting group description

BMS-986156 800mg Q2W

Reporting group title

Part B: BMS-986156 30mg + Nivo 240mg

Reporting group description

BMS986156 30mg Q2W + Nivo 240mg Q2W

Reporting group title

Part B: BMS-986156 100mg + Nivo 240mg

Reporting group description

BMS986156 100mg Q2W + Nivo 240mg Q2W

Reporting group title

Part B: BMS-986156 240mg + Nivo 240mg

Reporting group description

BMS986156 240mg Q2W + Nivo 240mg Q2W

Reporting group title

Part B: BMS-986156 800mg + Nivo 240mg

Reporting group description

BMS986156 800mg Q2W + Nivo 240mg Q2W

Reporting group title

Part D: BMS-986156 240mg + Nivo 240mg

Reporting group description

BMS986156 240mg Q2W + Nivo 240mg Q2W

Reporting group title

Part E: BMS-986156 480mg + Nivo 480mg

Reporting group description

BMS986156 480mg Q4W + Nivo 480mg Q4W

Primary: Number of participants with all cause adverse events (AEs), serious adverse events, AEs leading to discontinuation and deaths.

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End point title

Number of participants with all cause adverse events (AEs), serious adverse events, AEs leading to discontinuation and deaths. ^[1]

End point description

Number of participants with all cause adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, and number of participant deaths.

End point type

Primary

End point timeframe

Approximately up to 29 months

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis done for this endpoint

End point values	Part A: BMS-986156 10mg	Part A: BMS-986156 30mg	Part A: BMS-986156 100mg	Part A: BMS-986156 240mg	Part A: BMS-986156 800mg	Part C: BMS-986156 240mg	Part C: BMS-986156 800mg	Part B: BMS-986156 30mg + Nivo 240mg	Part B: BMS-986156 100mg + Nivo 240mg	Part B: BMS-986156 240mg + Nivo 240mg	Part B: BMS-986156 800mg + Nivo 240mg	Part D: BMS-986156 240mg + Nivo 240mg	Part E: BMS-986156 480mg + Nivo 480mg
Number of subjects analysed	4	6	4	6	9	3	2	3	9	14	11	188	33
Units: Participants
Adverse Events (AEs)	4	6	4	6	9	3	2	3	9	14	11	188	33
Serious Adverse Events (SAEs)	3	3	1	5	4	2	2	2	5	10	6	121	22
AEs leading to Discontinuation	1	2	0	2	1	0	0	0	1	2	1	32	5
Deaths	4	5	3	5	6	2	2	3	6	11	8	141	27

No statistical analyses for this end point

Primary: Number of Participants with laboratory abnormalities in specific thyroid tests

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End point title

Number of Participants with laboratory abnormalities in specific thyroid tests ^[2]

End point description

Number of Participants with laboratory abnormalities in specific thyroid tests. TSH = Thyroid stimulating hormone ULN = Upper limit number LLN = Lower limit number

End point type

Primary

End point timeframe

Approximately up to 29 months

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis done for this endpoint

End point values	Part A: BMS-986156 10mg	Part A: BMS-986156 30mg	Part A: BMS-986156 100mg	Part A: BMS-986156 240mg	Part A: BMS-986156 800mg	Part C: BMS-986156 240mg	Part C: BMS-986156 800mg	Part B: BMS-986156 30mg + Nivo 240mg	Part B: BMS-986156 100mg + Nivo 240mg	Part B: BMS-986156 240mg + Nivo 240mg	Part B: BMS-986156 800mg + Nivo 240mg	Part D: BMS-986156 240mg + Nivo 240mg	Part E: BMS-986156 480mg + Nivo 480mg
Number of subjects analysed	4	6	4	6	9	3	2	3	9	14	11	188	33
Units: Participants
TSH > ULN	1	2	0	2	2	0	0	1	1	4	5	72	19
TSH > ULN WITH TSH ≤ ULN AT BASELINE	0	0	0	0	0	0	0	1	0	4	2	42	11
TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN	0	0	0	0	0	0	0	0	0	0	0	37	9
TSH < LLN	0	0	0	0	0	0	0	0	1	4	2	38	10
TSH <LLN WITH TSH ≥ LLN AT BASELINE	0	0	0	0	0	0	0	0	0	3	2	26	8
TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN	0	0	1	0	0	0	0	0	0	1	1	25	5

No statistical analyses for this end point

Primary: Number of Participants with laboratory abnormalities in specific liver tests

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End point title

Number of Participants with laboratory abnormalities in specific liver tests ^[3]

End point description

Number of Participants with laboratory abnormalities in specific liver tests. ALT AST ALP T Bili = Total bilirubin

End point type

Primary

End point timeframe

Approximately up to 29 months

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis done for this endpoint

End point values	Part A: BMS-986156 10mg	Part A: BMS-986156 30mg	Part A: BMS-986156 100mg	Part A: BMS-986156 240mg	Part A: BMS-986156 800mg	Part C: BMS-986156 240mg	Part C: BMS-986156 800mg	Part B: BMS-986156 30mg + Nivo 240mg	Part B: BMS-986156 100mg + Nivo 240mg	Part B: BMS-986156 240mg + Nivo 240mg	Part B: BMS-986156 800mg + Nivo 240mg	Part D: BMS-986156 240mg + Nivo 240mg	Part E: BMS-986156 480mg + Nivo 480mg
Number of subjects analysed	4	6	4	6	9	3	2	3	9	13	11	188	33
Units: Participants
ALT OR AST > 3*ULN	0	1	0	0	1	0	0	0	1	3	2	25	3
ALT OR AST> 5*ULN	0	0	0	0	1	0	1	0	1	2	2	14	1
ALT OR AST> 10*ULN	0	0	0	0	0	0	0	0	0	2	0	6	0
ALT OR AST > 20*ULN	0	0	0	0	0	0	0	0	0	1	0	1	0
TOTAL BILIRUBIN > 2*ULN	0	1	0	0	0	0	0	1	0	1	0	5	1
ALP > 1.5*ULN	1	2	1	2	2	1	1	2	2	7	3	70	11
ALT/AST ELEV>3ULN; T BILI>2ULN IN 1 DAY	0	1	1	0	0	0	0	0	0	0	1	6	1
ALT/AST ELEV>3ULN;T BILI >2ULN IN 30 DAYS	0	1	1	0	0	0	0	0	0	0	1	7	1

No statistical analyses for this end point

Secondary: Best Overall Response

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End point title

Best Overall Response

End point description

Defined as the best response designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy.

End point type

Secondary

End point timeframe

Approximately 50 Months

End point values	Part A: BMS-986156 10mg	Part A: BMS-986156 30mg	Part A: BMS-986156 100mg	Part A: BMS-986156 240mg	Part A: BMS-986156 800mg	Part C: BMS-986156 240mg	Part C: BMS-986156 800mg	Part B: BMS-986156 30mg + Nivo 240mg	Part B: BMS-986156 100mg + Nivo 240mg	Part B: BMS-986156 240mg + Nivo 240mg	Part B: BMS-986156 800mg + Nivo 240mg	Part D: BMS-986156 240mg + Nivo 240mg	Part E: BMS-986156 480mg + Nivo 480mg
Number of subjects analysed	4	6	4	6	9	3	2	3	9	14	11	188	33
Units: Participants
Complete Response	0	0	0	0	0	0	0	0	0	0	0	4	2
Partial Response	0	0	0	0	0	0	0	1	1	3	1	17	1
Stable Disease	2	1	2	1	4	1	0	2	2	6	6	59	12
Progressive Disease	1	3	2	4	4	2	2	0	4	4	4	91	15
Not Evaluable	1	2	0	1	1	0	0	0	2	1	0	16	3
Not Available	0	0	0	0	0	0	0	0	0	0	0	1	0

No statistical analyses for this end point

Secondary: Overall Response Rate

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End point title

Overall Response Rate

End point description

Defined as the percentage of all treated participants whose BOR is either a complete response(CR) or partial response(PR).

End point type

Secondary

End point timeframe

Approximately 50 Months

Part A: BMS-986156 10mg

Part A: BMS-986156 30mg

Part A: BMS-986156 100mg

Part A: BMS-986156 240mg

Part A: BMS-986156 800mg

Part C: BMS-986156 240mg

Part C: BMS-986156 800mg

Part B: BMS-986156 30mg + Nivo 240mg

Part B: BMS-986156 100mg + Nivo 240mg

Part B: BMS-986156 240mg + Nivo 240mg

Part B: BMS-986156 800mg + Nivo 240mg

Part D: BMS-986156 240mg + Nivo 240mg

Part E: BMS-986156 480mg + Nivo 480mg

Number of subjects analysed

188

Units: Percentage of participants

number (confidence interval 95%)

0 (0.0 to 60.2)

0 (0.0 to 45.9)

0 (0.0 to 60.2)

0 (0.0 to 45.9)

0 (0.0 to 33.6)

0 (0.0 to 70.8)

0 (0.0 to 84.2)

0 (0.0 to 70.8)

11.1 (0.3 to 48.2)

21.4 (4.7 to 50.8)

9.1 (0.2 to 41.3)

11.2 (7.0 to 16.6)

9.1 (1.9 to 24.3)

No statistical analyses for this end point

Secondary: Progression Free Survival (PFS)

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End point title

Progression Free Survival (PFS)

End point description

The time from the first dosing date to the date of first objectively documented disease progression or death due to any cause, whichever occurs first. Here "-9999 and 9999" equals NA

End point type

Secondary

End point timeframe

Approximately 50 Months

Part A: BMS-986156 10mg

Part A: BMS-986156 30mg

Part A: BMS-986156 100mg

Part A: BMS-986156 240mg

Part A: BMS-986156 800mg

Part C: BMS-986156 240mg

Part C: BMS-986156 800mg

Part B: BMS-986156 30mg + Nivo 240mg

Part B: BMS-986156 100mg + Nivo 240mg

Part B: BMS-986156 240mg + Nivo 240mg

Part B: BMS-986156 800mg + Nivo 240mg

Part D: BMS-986156 240mg + Nivo 240mg

Part E: BMS-986156 480mg + Nivo 480mg

Number of subjects analysed

188

Units: Months

median (confidence interval 95%)

3.48 (1.64 to 9999)

1.74 (1.45 to 9999)

2.66 (1.64 to 9999)

1.64 (1.58 to 9999)

1.84 (1.64 to 3.48)

1.64 (1.64 to 9999)

1.71 (-9999 to 9999)

1.81 (1.64 to 9999)

1.64 (0.89 to 22.47)

3.71 (1.64 to 8.97)

3.52 (1.61 to 9999)

1.91 (1.81 to 3.25)

2.92 (1.77 to 3.52)

No statistical analyses for this end point

Secondary: Duration of Response

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End point title

Duration of Response

End point description

All treated participants with a BOR of CR or PR, is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first. Here "0.9999 and 21.9999" indicate values not calculable.

End point type

Secondary

End point timeframe

Approximately 50 Months

Part A: BMS-986156 10mg

Part A: BMS-986156 30mg

Part A: BMS-986156 100mg

Part A: BMS-986156 240mg

Part A: BMS-986156 800mg

Part C: BMS-986156 240mg

Part C: BMS-986156 800mg

Part B: BMS-986156 30mg + Nivo 240mg

Part B: BMS-986156 100mg + Nivo 240mg

Part B: BMS-986156 240mg + Nivo 240mg

Part B: BMS-986156 800mg + Nivo 240mg

Part D: BMS-986156 240mg + Nivo 240mg

Part E: BMS-986156 480mg + Nivo 480mg

Number of subjects analysed

0 ^[4]

0 ^[5]

0 ^[6]

0 ^[7]

0 ^[8]

0 ^[9]

0 ^[10]

0 ^[11]

1 ^[12]

3 ^[13]

Units: Months

median (full range (min-max))

( to )

20.70 (20.7 to 20.7)

30.10 (7.4 to 31.3)

31.0 (31.0 to 31.0)

0.9999 (0.0 to 31.8)

21.9999 (21.0 to 22.4)

Notes
[4] - No subjects analyzed
[5] - No subjects analyzed
[6] - No subjects analyzed
[7] - No subjects analyzed
[8] - No subjects analyzed
[9] - No subjects analyzed
[10] - No subjects analyzed
[11] - No subjects analyzed
[12] - Median value not calculable
[13] - Median value not calculable

No statistical analyses for this end point

Secondary: Number of Participants with Anti-Drug Antibody Response

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End point title

Number of Participants with Anti-Drug Antibody Response

End point description

Number of participants with a positive Anti-Drug Antibody to BMS-986156 or nivolumab Here "9999" means not available. subjects did not receive nivolumab

End point type

Secondary

End point timeframe

At Cycle 3 Day 1 (Approximately 30 days)

End point values	Part A: BMS-986156 10mg	Part A: BMS-986156 30mg	Part A: BMS-986156 100mg	Part A: BMS-986156 240mg	Part A: BMS-986156 800mg	Part C: BMS-986156 240mg	Part C: BMS-986156 800mg	Part B: BMS-986156 30mg + Nivo 240mg	Part B: BMS-986156 100mg + Nivo 240mg	Part B: BMS-986156 240mg + Nivo 240mg	Part B: BMS-986156 800mg + Nivo 240mg	Part D: BMS-986156 240mg + Nivo 240mg	Part E: BMS-986156 480mg + Nivo 480mg
Number of subjects analysed	4	6	4	6	9	3	2	3	9	14	11	188	33
Units: Participants
BMS-986156	1	0	0	0	0	0	0	1	0	0	0	5	0
Nivolumab	9999	9999	9999	9999	9999	9999	9999	0	0	4	1	32	2

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs/SAEs are collected from the first dose date until the last dose date + 100 days. (Approximately up to 29 months)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Part A: BMS-986156 10mg

Reporting group description

BMS986156 10mg Q2W

Reporting group title

Part A: BMS-986156 30mg

Reporting group description

BMS986156 30mg Q2W

Reporting group title

Part A: BMS-986156 100mg

Reporting group description

BMS-986156 100mg Q2W

Reporting group title

Part A: BMS-986156 240mg

Reporting group description

BMS-986156 240mg Q2W

Reporting group title

Part C: BMS-986156 240mg

Reporting group description

BMS-986156 240mg Q2W

Reporting group title

Part A: BMS-986156 800mg

Reporting group description

BMS-986156 800mg Q2W

Reporting group title

Part C: BMS-986156 800mg

Reporting group description

BMS-986156 240mg Q2W

Reporting group title

Part B: BMS-986156 30mg +Nivo 240mg

Reporting group description

BMS-986156 30mg Q2W +Nivo 240mg Q2W

Reporting group title

Part B: BMS-986156 100mg +Nivo 240mg

Reporting group description

BMS-986156 100mg Q2W +Nivo 240mg Q2W

Reporting group title

Part B: BMS-986156 240mg +Nivo 240mg

Reporting group description

BMS-986156 240mg Q2W +Nivo 240mg Q2W

Reporting group title

Part B: BMS-986156 800mg +Nivo 240mg

Reporting group description

BMS-986156 800mg Q2W +Nivo 240mg Q2W

Reporting group title

Part D: BMS-986156 240mg +Nivo 240mg

Reporting group description

BMS-986156 240mg Q2W +Nivo 240mg Q2W

Reporting group title

Part E: BMS-986156 480mg Q4W +Nivo 480mg Q4W

Reporting group description

BMS-986156 480mg Q4W +Nivo 480mg Q4W

Part A: BMS-986156 10mg

Part A: BMS-986156 30mg

Part A: BMS-986156 100mg

Part A: BMS-986156 240mg

Part C: BMS-986156 240mg

Part A: BMS-986156 800mg

Part C: BMS-986156 800mg

Part B: BMS-986156 30mg +Nivo 240mg

Part B: BMS-986156 100mg +Nivo 240mg

Part B: BMS-986156 240mg +Nivo 240mg

Part B: BMS-986156 800mg +Nivo 240mg

Part D: BMS-986156 240mg +Nivo 240mg

Part E: BMS-986156 480mg Q4W +Nivo 480mg Q4W

Total subjects affected by serious adverse events

subjects affected / exposed

3 / 4 (75.00%)

3 / 6 (50.00%)

1 / 4 (25.00%)

5 / 6 (83.33%)

2 / 3 (66.67%)

4 / 9 (44.44%)

2 / 2 (100.00%)

2 / 3 (66.67%)

5 / 9 (55.56%)

10 / 14 (71.43%)

6 / 11 (54.55%)

121 / 188 (64.36%)

22 / 33 (66.67%)

number of deaths (all causes)

141

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Cancer pain

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

3 / 188 (1.60%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant ascites

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Malignant neoplasm progression

subjects affected / exposed

3 / 4 (75.00%)

2 / 6 (33.33%)

1 / 4 (25.00%)

2 / 6 (33.33%)

1 / 3 (33.33%)

3 / 9 (33.33%)

2 / 2 (100.00%)

2 / 3 (66.67%)

3 / 9 (33.33%)

4 / 14 (28.57%)

2 / 11 (18.18%)

72 / 188 (38.30%)

13 / 33 (39.39%)

occurrences causally related to treatment / all

0 / 3

0 / 2

0 / 1

0 / 2

0 / 1

0 / 3

0 / 2

0 / 3

0 / 4

0 / 2

0 / 74

0 / 13

deaths causally related to treatment / all

0 / 3

0 / 2

0 / 1

0 / 2

0 / 1

0 / 3

0 / 2

0 / 3

0 / 4

0 / 2

0 / 63

0 / 12

Metastases to central nervous system

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Metastases to pancreas

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neoplasm malignant

subjects affected / exposed

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Tumour haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour pain

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

6 / 188 (3.19%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 6

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Arterial occlusive disease

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Deep vein thrombosis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

General disorders and administration site conditions

Disease progression

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Fatigue

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General physical health deterioration

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

2 / 188 (1.06%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 1

deaths causally related to treatment / all

0 / 0

Inflammation

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Non-cardiac chest pain

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

7 / 188 (3.72%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 8

0 / 0

deaths causally related to treatment / all

0 / 0

Performance status decreased

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

2 / 14 (14.29%)

0 / 11 (0.00%)

2 / 188 (1.06%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

Perineal pain

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Uterine haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Chronic obstructive pulmonary disease

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (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

Dyspnoea

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

2 / 14 (14.29%)

0 / 11 (0.00%)

5 / 188 (2.66%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 5

0 / 1

deaths causally related to treatment / all

0 / 0

Haemoptysis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Obstructive airways disorder

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Pleural effusion

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

5 / 188 (2.66%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 7

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia aspiration

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Pneumonitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 9 (11.11%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumothorax

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

1 / 11 (9.09%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

0 / 11 (0.00%)

6 / 188 (3.19%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 6

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory failure

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Confusional state

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

1 / 11 (9.09%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Blood creatine phosphokinase increased

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

1 / 11 (9.09%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood creatinine increased

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

General physical condition abnormal

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic enzyme increased

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

1 / 11 (9.09%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Femur fracture

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

1 / 11 (9.09%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infusion related reaction

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

5 / 188 (2.66%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

5 / 5

0 / 0

deaths causally related to treatment / all

0 / 0

Lower limb fracture

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Spinal fracture

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

2 / 188 (1.06%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Stoma obstruction

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Stoma site extravasation

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Stoma site pain

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Atrial fibrillation

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial flutter

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrioventricular block complete

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardio-respiratory arrest

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Endocarditis noninfective

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Myocardial infarction

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pericardial effusion

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Ataxia

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

1 / 9 (11.11%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebral haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebrovascular accident

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 2 (50.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dizziness

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

2 / 188 (1.06%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Encephalopathy

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Facial paralysis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemorrhage intracranial

subjects affected / exposed

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Paraesthesia

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 9 (11.11%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Seizure

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Spinal cord compression

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Syncope

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Thalamus haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Transient ischaemic attack

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

2 / 188 (1.06%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

2 / 188 (1.06%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 1

deaths causally related to treatment / all

0 / 0

Bone marrow failure

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Febrile neutropenia

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

1 / 11 (9.09%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Gastrointestinal disorders

Abdominal distension

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal pain

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

0 / 11 (0.00%)

6 / 188 (3.19%)

2 / 33 (6.06%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 6

0 / 2

deaths causally related to treatment / all

0 / 0

Abdominal pain upper

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ascites

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

2 / 188 (1.06%)

3 / 33 (9.09%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 6

0 / 4

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

0 / 11 (0.00%)

2 / 188 (1.06%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Diarrhoea

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 9 (11.11%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

1 / 11 (9.09%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dysphagia

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

3 / 188 (1.60%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 1

deaths causally related to treatment / all

0 / 0

Haematochezia

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ileus

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

2 / 188 (1.06%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 1

deaths causally related to treatment / all

0 / 0

Intestinal obstruction

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

5 / 188 (2.66%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 6

0 / 1

deaths causally related to treatment / all

0 / 0

Large intestinal obstruction

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

1 / 9 (11.11%)

0 / 14 (0.00%)

1 / 11 (9.09%)

2 / 188 (1.06%)

2 / 33 (6.06%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

deaths causally related to treatment / all

0 / 0

Pancreatitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Rectal haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rectal perforation

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

3 / 188 (1.60%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 1

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 9 (11.11%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

0 / 11 (0.00%)

0 / 188 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Bile duct obstruction

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholangitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic pain

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperbilirubinaemia

subjects affected / exposed

0 / 4 (0.00%)

1 / 6 (16.67%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

Skin lesion

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

0 / 11 (0.00%)

2 / 188 (1.06%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Haematuria

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hydronephrosis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nephritis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

1 / 9 (11.11%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ureteric haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract obstruction

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

3 / 188 (1.60%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Urogenital fistula

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endocrine disorders

Ectopic antidiuretic hormone secretion

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Thyroid mass

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Back pain

subjects affected / exposed

1 / 4 (25.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

1 / 11 (9.09%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Bone pain

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

1 / 6 (16.67%)

1 / 3 (33.33%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neck pain

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

1 / 11 (9.09%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain in extremity

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pathological fracture

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Abdominal infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

1 / 9 (11.11%)

0 / 14 (0.00%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Biliary tract infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Clostridium difficile infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Extradural abscess

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Kidney infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

2 / 33 (6.06%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 3

deaths causally related to treatment / all

0 / 0

Neutropenic sepsis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Osteomyelitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pharyngitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

6 / 188 (3.19%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 8

0 / 1

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory tract infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

1 / 14 (7.14%)

0 / 11 (0.00%)

0 / 188 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

3 / 188 (1.60%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Septic shock

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Soft tissue infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal cord infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Streptococcal infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper respiratory tract infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

5 / 188 (2.66%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 6

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Dehydration

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

1 / 3 (33.33%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypocalcaemia

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Hypokalaemia

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyponatraemia

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

2 / 188 (1.06%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Type 1 diabetes mellitus

subjects affected / exposed

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 4 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 9 (0.00%)

0 / 14 (0.00%)

0 / 11 (0.00%)

1 / 188 (0.53%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Part A: BMS-986156 10mg	Part A: BMS-986156 30mg	Part A: BMS-986156 100mg	Part A: BMS-986156 240mg	Part C: BMS-986156 240mg	Part A: BMS-986156 800mg	Part C: BMS-986156 800mg	Part B: BMS-986156 30mg +Nivo 240mg	Part B: BMS-986156 100mg +Nivo 240mg	Part B: BMS-986156 240mg +Nivo 240mg	Part B: BMS-986156 800mg +Nivo 240mg	Part D: BMS-986156 240mg +Nivo 240mg	Part E: BMS-986156 480mg Q4W +Nivo 480mg Q4W
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 4 (100.00%)	5 / 6 (83.33%)	4 / 4 (100.00%)	6 / 6 (100.00%)	3 / 3 (100.00%)	9 / 9 (100.00%)	1 / 2 (50.00%)	2 / 3 (66.67%)	8 / 9 (88.89%)	14 / 14 (100.00%)	11 / 11 (100.00%)	185 / 188 (98.40%)	31 / 33 (93.94%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	1 / 11 (9.09%)	11 / 188 (5.85%)	2 / 33 (6.06%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	1	11	2
Tumour pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	11 / 188 (5.85%)	2 / 33 (6.06%)
occurrences all number	0	0	0	1	0	0	1	0	0	0	0	12	2
Vascular disorders
Embolism
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	2
Hot flush
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	2 / 188 (1.06%)	3 / 33 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	2	3
Hypertension
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	1 / 11 (9.09%)	6 / 188 (3.19%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	7	0
Hypotension
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	5 / 188 (2.66%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	5	1
Orthostatic hypotension
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1
Vascular compression
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	27 / 188 (14.36%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	29	0
Catheter site erythema
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0
Chest discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	4 / 188 (2.13%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	8	0
Chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	11 / 188 (5.85%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	11	0
Chills
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	4 / 14 (28.57%)	2 / 11 (18.18%)	15 / 188 (7.98%)	2 / 33 (6.06%)
occurrences all number	0	0	1	1	0	1	0	0	2	4	2	16	3
Early satiety
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0
Fatigue
subjects affected / exposed	2 / 4 (50.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	2 / 6 (33.33%)	2 / 3 (66.67%)	3 / 9 (33.33%)	1 / 2 (50.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	5 / 14 (35.71%)	7 / 11 (63.64%)	57 / 188 (30.32%)	15 / 33 (45.45%)
occurrences all number	3	2	1	2	2	3	1	1	1	5	7	64	16
Feeling abnormal
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Feeling hot
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	1	0
Gait disturbance
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	1 / 11 (9.09%)	1 / 188 (0.53%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	2	1
Influenza like illness
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 14 (14.29%)	1 / 11 (9.09%)	11 / 188 (5.85%)	1 / 33 (3.03%)
occurrences all number	1	0	0	0	0	1	0	0	0	3	1	13	1
Malaise
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	2 / 11 (18.18%)	5 / 188 (2.66%)	0 / 33 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0	3	5	0
Non-cardiac chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	4 / 188 (2.13%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	4	0
Oedema peripheral
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	2 / 9 (22.22%)	1 / 2 (50.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	1 / 14 (7.14%)	3 / 11 (27.27%)	25 / 188 (13.30%)	6 / 33 (18.18%)
occurrences all number	0	0	0	2	0	2	1	1	1	1	3	25	9
Pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	17 / 188 (9.04%)	0 / 33 (0.00%)
occurrences all number	0	0	1	0	2	1	0	0	0	0	1	17	0
Pyrexia
subjects affected / exposed	2 / 4 (50.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	3 / 6 (50.00%)	0 / 3 (0.00%)	3 / 9 (33.33%)	0 / 2 (0.00%)	2 / 3 (66.67%)	3 / 9 (33.33%)	5 / 14 (35.71%)	5 / 11 (45.45%)	34 / 188 (18.09%)	3 / 33 (9.09%)
occurrences all number	2	0	0	3	0	3	0	3	3	6	6	41	3
Reproductive system and breast disorders
Breast tenderness
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0	0	0
Dysmenorrhoea
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0
Scrotal oedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Testicular pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0
Vaginal discharge
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1
Vaginal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	4 / 188 (2.13%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	9	2
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	1 / 3 (33.33%)	2 / 9 (22.22%)	5 / 14 (35.71%)	1 / 11 (9.09%)	31 / 188 (16.49%)	7 / 33 (21.21%)
occurrences all number	1	0	0	0	0	1	0	1	2	5	1	38	7
Dry throat
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0
Dysphonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	6 / 188 (3.19%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	7	0
Dyspnoea
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	2 / 9 (22.22%)	1 / 2 (50.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	1 / 14 (7.14%)	2 / 11 (18.18%)	29 / 188 (15.43%)	6 / 33 (18.18%)
occurrences all number	0	0	0	1	1	2	1	1	0	1	2	31	6
Dyspnoea exertional
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	5 / 188 (2.66%)	3 / 33 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	5	3
Epistaxis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	5 / 188 (2.66%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	5	1
Nasal congestion
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	4 / 188 (2.13%)	3 / 33 (9.09%)
occurrences all number	0	1	0	0	0	0	0	1	0	1	0	4	3
Nasal discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	7 / 188 (3.72%)	3 / 33 (9.09%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	7	3
Pleural effusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	6 / 188 (3.19%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	11	1
Pneumonitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2
Productive cough
subjects affected / exposed	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	7 / 188 (3.72%)	4 / 33 (12.12%)
occurrences all number	1	1	0	0	0	1	0	0	0	0	0	7	4
Rhinorrhoea
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 14 (7.14%)	0 / 11 (0.00%)	3 / 188 (1.60%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	3	0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	3 / 14 (21.43%)	1 / 11 (9.09%)	7 / 188 (3.72%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	1	4	1	7	1
Confusional state
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0
Depressed mood
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1
Depression
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 14 (7.14%)	0 / 11 (0.00%)	6 / 188 (3.19%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	6	0
Insomnia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	3 / 14 (21.43%)	0 / 11 (0.00%)	12 / 188 (6.38%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	1	0	0	0	1	7	0	12	1
Mood altered
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Sleep disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 14 (14.29%)	1 / 11 (9.09%)	8 / 188 (4.26%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	4	1	10	1
Amylase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	7 / 188 (3.72%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	7	1
Aspartate aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	1 / 11 (9.09%)	11 / 188 (5.85%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	2	14	2
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	3 / 188 (1.60%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	3	0	3	0
Blood bilirubin increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	1 / 11 (9.09%)	4 / 188 (2.13%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	6	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	4 / 188 (2.13%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	4	0
Blood creatinine increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	1 / 9 (11.11%)	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	2 / 14 (14.29%)	0 / 11 (0.00%)	11 / 188 (5.85%)	1 / 33 (3.03%)
occurrences all number	0	0	0	1	1	1	0	1	0	2	0	17	1
Blood potassium decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0
Lipase increased
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	7 / 188 (3.72%)	1 / 33 (3.03%)
occurrences all number	1	0	0	1	0	0	0	0	8	0	0	9	1
Neutrophil count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	1	0
Platelet count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	2 / 188 (1.06%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	2	1
Weight decreased
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 14 (7.14%)	0 / 11 (0.00%)	9 / 188 (4.79%)	2 / 33 (6.06%)
occurrences all number	0	1	0	0	0	2	0	0	1	1	0	9	2
Weight increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	2 / 188 (1.06%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	2	1
Injury, poisoning and procedural complications
Abdominal injury
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0
Fall
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	1 / 188 (0.53%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	2
Infusion related reaction
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 2 (50.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 14 (7.14%)	2 / 11 (18.18%)	20 / 188 (10.64%)	6 / 33 (18.18%)
occurrences all number	0	0	0	0	0	2	1	0	1	1	3	24	6
Post procedural haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2
Procedural pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	4 / 188 (2.13%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	4	1
Rib fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Stoma site pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	10 / 188 (5.32%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	1	0	0	0	0	3	0	12	4
Dysgeusia
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 188 (0.53%)	1 / 33 (3.03%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	1	1
Headache
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	5 / 14 (35.71%)	3 / 11 (27.27%)	22 / 188 (11.70%)	3 / 33 (9.09%)
occurrences all number	1	0	1	3	0	2	0	0	0	10	6	33	3
Lethargy
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Migraine
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0
Myoclonus
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Neuralgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0
Neuropathy peripheral
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 14 (14.29%)	1 / 11 (9.09%)	6 / 188 (3.19%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	1	7	0
Paraesthesia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	4 / 188 (2.13%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	0	1	4	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	4 / 14 (28.57%)	0 / 11 (0.00%)	2 / 188 (1.06%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	5	0	2	1
Somnolence
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	3 / 14 (21.43%)	2 / 11 (18.18%)	30 / 188 (15.96%)	5 / 33 (15.15%)
occurrences all number	0	0	0	0	2	1	0	1	0	3	2	35	5
Increased tendency to bruise
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0
Thrombocytosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	1	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	1 / 188 (0.53%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	2	1
Eye disorders
Dry eye
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	1 / 11 (9.09%)	2 / 188 (1.06%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	2	2
Eye discharge
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	1	0
Eye pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1
Periorbital swelling
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Vision blurred
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	3 / 188 (1.60%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	3	1
Visual impairment
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	2 / 188 (1.06%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	2	0
Abdominal distension
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	10 / 188 (5.32%)	2 / 33 (6.06%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0	12	2
Abdominal pain
subjects affected / exposed	0 / 4 (0.00%)	3 / 6 (50.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	3 / 9 (33.33%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	3 / 14 (21.43%)	2 / 11 (18.18%)	22 / 188 (11.70%)	9 / 33 (27.27%)
occurrences all number	0	3	0	2	0	3	0	0	3	3	2	25	9
Abdominal pain lower
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	5 / 188 (2.66%)	1 / 33 (3.03%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	1	6	1
Abdominal pain upper
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	8 / 188 (4.26%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	11	0
Anal incontinence
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Ascites
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	10 / 188 (5.32%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	14	2
Colitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Constipation
subjects affected / exposed	2 / 4 (50.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	2 / 6 (33.33%)	1 / 3 (33.33%)	2 / 9 (22.22%)	0 / 2 (0.00%)	0 / 3 (0.00%)	3 / 9 (33.33%)	1 / 14 (7.14%)	2 / 11 (18.18%)	28 / 188 (14.89%)	7 / 33 (21.21%)
occurrences all number	2	3	1	2	3	2	0	0	3	1	2	29	7
Diarrhoea
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	4 / 9 (44.44%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	4 / 14 (28.57%)	3 / 11 (27.27%)	35 / 188 (18.62%)	6 / 33 (18.18%)
occurrences all number	0	1	1	0	2	5	0	0	4	8	4	51	7
Dry mouth
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	2 / 14 (14.29%)	0 / 11 (0.00%)	4 / 188 (2.13%)	6 / 33 (18.18%)
occurrences all number	0	0	0	0	0	0	0	0	1	3	0	4	6
Dyspepsia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	3 / 188 (1.60%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	4	0
Dysphagia
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	7 / 188 (3.72%)	2 / 33 (6.06%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	1	7	2
Eructation
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	4 / 188 (2.13%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	4	2
Gingival bleeding
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 14 (14.29%)	0 / 11 (0.00%)	0 / 188 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	5	0	0	1
Intestinal obstruction
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Lip dry
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Lower gastrointestinal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0
Mesenteric vein thrombosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Nausea
subjects affected / exposed	2 / 4 (50.00%)	3 / 6 (50.00%)	1 / 4 (25.00%)	3 / 6 (50.00%)	1 / 3 (33.33%)	2 / 9 (22.22%)	0 / 2 (0.00%)	0 / 3 (0.00%)	4 / 9 (44.44%)	5 / 14 (35.71%)	5 / 11 (45.45%)	44 / 188 (23.40%)	12 / 33 (36.36%)
occurrences all number	3	3	1	4	1	2	0	0	5	9	5	59	16
Stomatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	1 / 188 (0.53%)	4 / 33 (12.12%)
occurrences all number	0	0	0	1	0	0	0	0	0	2	0	1	5
Toothache
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	2 / 188 (1.06%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	2	1
Vomiting
subjects affected / exposed	1 / 4 (25.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	3 / 9 (33.33%)	0 / 2 (0.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	8 / 14 (57.14%)	2 / 11 (18.18%)	28 / 188 (14.89%)	8 / 33 (24.24%)
occurrences all number	1	1	1	0	2	4	0	1	1	11	3	53	11
Hepatobiliary disorders
Hepatic pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	4 / 188 (2.13%)	1 / 33 (3.03%)
occurrences all number	0	0	0	1	0	1	0	0	0	0	0	4	1
Dermatitis acneiform
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	1 / 11 (9.09%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	1	0
Dermatitis exfoliative generalised
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Dry skin
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	7 / 188 (3.72%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	8	0
Eczema
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0
Erythema
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	6 / 188 (3.19%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	7	0
Hyperhidrosis
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	2 / 188 (1.06%)	1 / 33 (3.03%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	2	1
Nail ridging
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	1	0
Night sweats
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	2 / 188 (1.06%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	2	0	2	0
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	2 / 11 (18.18%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	1	0
Pruritus
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	2 / 14 (14.29%)	0 / 11 (0.00%)	21 / 188 (11.17%)	1 / 33 (3.03%)
occurrences all number	0	1	0	0	0	0	0	1	1	2	0	27	1
Rash
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 14 (14.29%)	0 / 11 (0.00%)	15 / 188 (7.98%)	3 / 33 (9.09%)
occurrences all number	0	0	0	0	1	0	0	0	0	2	0	15	3
Rash macular
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	2 / 188 (1.06%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	2	0
Rash maculo-papular
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	6 / 188 (3.19%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	6	2
Sensitive skin
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0
Urticaria
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Dysuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	6 / 188 (3.19%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	6	1
Haematuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	5 / 188 (2.66%)	1 / 33 (3.03%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	6	1
Haemorrhage urinary tract
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0
Hydronephrosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1
Kidney congestion
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0
Nephritis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0
Urinary retention
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	3 / 188 (1.60%)	1 / 33 (3.03%)
occurrences all number	0	0	0	2	0	0	0	0	1	0	0	3	1
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	10 / 188 (5.32%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	12	0
Hypothyroidism
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	11 / 188 (5.85%)	3 / 33 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	15	3
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	3 / 14 (21.43%)	3 / 11 (27.27%)	20 / 188 (10.64%)	5 / 33 (15.15%)
occurrences all number	1	0	0	0	0	1	0	0	1	3	3	22	5
Back pain
subjects affected / exposed	1 / 4 (25.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	2 / 14 (14.29%)	5 / 11 (45.45%)	25 / 188 (13.30%)	4 / 33 (12.12%)
occurrences all number	1	1	1	2	0	1	0	0	1	3	5	26	4
Bone pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	3 / 188 (1.60%)	0 / 33 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	1	0	0	3	0
Flank pain
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	8 / 188 (4.26%)	5 / 33 (15.15%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	1	8	5
Groin pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	5 / 188 (2.66%)	0 / 33 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	5	0
Muscle spasms
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	5 / 188 (2.66%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	5	2
Muscular weakness
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	1 / 14 (7.14%)	1 / 11 (9.09%)	9 / 188 (4.79%)	3 / 33 (9.09%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	1	9	3
Musculoskeletal chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 14 (14.29%)	0 / 11 (0.00%)	2 / 188 (1.06%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	3	0	2	2
Musculoskeletal discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	1 / 188 (0.53%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	1	1
Musculoskeletal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	4 / 188 (2.13%)	2 / 33 (6.06%)
occurrences all number	0	0	0	2	2	0	0	0	0	0	1	4	2
Myalgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	2 / 14 (14.29%)	4 / 11 (36.36%)	11 / 188 (5.85%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	1	0	0	2	2	4	11	2
Neck pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	1 / 11 (9.09%)	5 / 188 (2.66%)	2 / 33 (6.06%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	1	5	2
Pain in extremity
subjects affected / exposed	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 14 (7.14%)	0 / 11 (0.00%)	15 / 188 (7.98%)	4 / 33 (12.12%)
occurrences all number	1	1	0	1	0	1	0	0	1	1	0	16	4
Pain in jaw
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 14 (14.29%)	0 / 11 (0.00%)	2 / 188 (1.06%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	2	0
Synovial cyst
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0
Infections and infestations
Cellulitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	2	0
Ear infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 188 (0.53%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	2
Epididymitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Furuncle
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0
Gastroenteritis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0
Gingivitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0
Herpes simplex
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0
Lower respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0
Oral candidiasis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1
Oral herpes
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1
Otitis externa
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	2 / 188 (1.06%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	2	0
Otitis media
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	2 / 188 (1.06%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	2	0
Pharyngitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	2 / 188 (1.06%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	2	0
Pneumonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 14 (7.14%)	0 / 11 (0.00%)	3 / 188 (1.60%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	3	2
Respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	2 / 188 (1.06%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	2	0
Rhinitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	2 / 188 (1.06%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	2	1
Sinusitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	4 / 188 (2.13%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	4	0
Tooth infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	2	0
Upper respiratory tract infection
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	2 / 14 (14.29%)	2 / 11 (18.18%)	8 / 188 (4.26%)	1 / 33 (3.03%)
occurrences all number	1	0	0	0	0	1	0	0	1	2	2	9	1
Urinary tract infection
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	1 / 14 (7.14%)	0 / 11 (0.00%)	11 / 188 (5.85%)	4 / 33 (12.12%)
occurrences all number	1	0	0	0	0	0	0	0	7	1	0	15	5
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 4 (25.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	2 / 9 (22.22%)	1 / 2 (50.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	5 / 14 (35.71%)	4 / 11 (36.36%)	34 / 188 (18.09%)	5 / 33 (15.15%)
occurrences all number	1	2	0	1	2	2	1	1	1	9	4	34	5
Dehydration
subjects affected / exposed	1 / 4 (25.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	4 / 188 (2.13%)	0 / 33 (0.00%)
occurrences all number	1	1	0	0	1	0	0	0	0	1	0	5	0
Gout
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0
Hypercalcaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	7 / 188 (3.72%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	10	1
Hypoalbuminaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	1 / 11 (9.09%)	1 / 188 (0.53%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	1	0
Hypokalaemia
subjects affected / exposed	0 / 4 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	7 / 188 (3.72%)	2 / 33 (6.06%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	7	3
Hypomagnesaemia
subjects affected / exposed	1 / 4 (25.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 2 (0.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	1 / 14 (7.14%)	0 / 11 (0.00%)	9 / 188 (4.79%)	2 / 33 (6.06%)
occurrences all number	1	0	0	0	1	0	0	1	1	2	0	10	2
Hyponatraemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	6 / 188 (3.19%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	7	2
Hypophosphataemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 14 (0.00%)	0 / 11 (0.00%)	6 / 188 (3.19%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	8	0
Steroid diabetes
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 14 (7.14%)	0 / 11 (0.00%)	0 / 188 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0
Vitamin D deficiency
subjects affected / exposed	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 14 (0.00%)	0 / 11 (0.00%)	0 / 188 (0.00%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2

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Were there any global substantial amendments to the protocol? Yes

18 Jul 2016

Identification of additional tumor types to be explored during Part D of the study design Revision of tumor types to be explored Starting dose of BMS-936558 in combination with Nivolumab clarified Dose duration of Nivolumab for Part B & D included

16 Sep 2016

The purpose of this amendment is to address HA feedback and to make clarifying changes. Provides clarification for further dose options for BMS-986156 Updates sections of the protocol with the latest safety data for BMS- 986156 monotherapy and BMS-986156 in combination with nivolumab Clarifies effective methods of contraception Restrict the population of NSCLC subjects to those with progressive or recurrent disease after prior platinum doublet-based chemotherapy Modify inclusion criteria for subjects with bladder cancer and ovarian cancer Added additional PD assessments

31 Jan 2017

The changes in this amendment include addition of dose expansion cohorts using every 4 week dosing in cervical cancer and in a multitumor type cohort including tumors allowed in dose escalation in combination of BMS 986156 with nivolumab, Clarifies inclusion criteria for the SCCHN, HCC and ovarian cancer cohorts, Updates clinical safety information, Updates the statistical section Updates the contraceptive language Added additional PD assessments

22 Nov 2017

The changes in this amendment include extending treatment for up to total of 2 years, or up to 7 additional cycles.

08 Mar 2019

This revision reflects to following changes:  Incorporates Administrative Letter 04  Halts all PK, PD, immunogenicity, and biomarker sampling and analyses  Removes the Response and Survival Follow-up Phases  Removes Retreatment option during Survival follow-up  Includes minor typographical changes throughout

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results:
A Phase 1/2a Dose Escalation and Cohort Expansion Study for Safety, Tolerability, and Efficacy of BMS-986156 Administered Alone and in Combination with Nivolumab (BMS-936558, anti PD-1 Monoclonal Antibody) in Advanced Solid Tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with all cause adverse events (AEs), serious adverse events, AEs leading to discontinuation and deaths.

Primary: Number of participants with all cause adverse events (AEs), serious adverse events, AEs leading to discontinuation and deaths.

Primary: Number of Participants with laboratory abnormalities in specific thyroid tests

Primary: Number of Participants with laboratory abnormalities in specific thyroid tests

Primary: Number of Participants with laboratory abnormalities in specific liver tests

Primary: Number of Participants with laboratory abnormalities in specific liver tests

Secondary: Best Overall Response

Secondary: Best Overall Response

Secondary: Overall Response Rate

Secondary: Overall Response Rate

Secondary: Progression Free Survival (PFS)

Secondary: Progression Free Survival (PFS)

Secondary: Duration of Response

Secondary: Duration of Response

Secondary: Number of Participants with Anti-Drug Antibody Response

Secondary: Number of Participants with Anti-Drug Antibody Response

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical trials

Clinical Trial Results: A Phase 1/2a Dose Escalation and Cohort Expansion Study for Safety, Tolerability, and Efficacy of BMS-986156 Administered Alone and in Combination with Nivolumab (BMS-936558, anti PD-1 Monoclonal Antibody) in Advanced Solid Tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of participants with all cause adverse events (AEs), serious adverse events, AEs leading to discontinuation and deaths.

Primary: Number of participants with all cause adverse events (AEs), serious adverse events, AEs leading to discontinuation and deaths.

Primary: Number of Participants with laboratory abnormalities in specific thyroid tests

Primary: Number of Participants with laboratory abnormalities in specific thyroid tests

Primary: Number of Participants with laboratory abnormalities in specific liver tests

Primary: Number of Participants with laboratory abnormalities in specific liver tests

Secondary: Best Overall Response

Secondary: Best Overall Response

Secondary: Overall Response Rate

Secondary: Overall Response Rate

Secondary: Progression Free Survival (PFS)

Secondary: Progression Free Survival (PFS)

Secondary: Duration of Response

Secondary: Duration of Response

Secondary: Number of Participants with Anti-Drug Antibody Response

Secondary: Number of Participants with Anti-Drug Antibody Response

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 1/2a Dose Escalation and Cohort Expansion Study for Safety, Tolerability, and Efficacy of BMS-986156 Administered Alone and in Combination with Nivolumab (BMS-936558, anti PD-1 Monoclonal Antibody) in Advanced Solid Tumors