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Clinical Trial Results:
A Phase I/II Multi-centre Study of AZD8931 in Combination with Weekly Paclitaxel to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy in Patients with Advanced Solid Tumours and in a Selected Population with Low HER2-expressing Locally Recurrent and/or Metastatic Breast Cancer (THYME)

Summary
EudraCT number	2009-010551-26
Trial protocol	GB CZ HU SE FR IT BG BE
Global end of trial date	05 Feb 2015

Results information
Results version number	v1(current)
This version publication date	23 Apr 2016
First version publication date	23 Apr 2016
Other versions

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

D0102C00003

ISRCTN number

-

US NCT number

-

WHO universal trial number (UTN)

-

Sponsor organisation name

Astrazeneca

Sponsor organisation address

Macclesfield, Cheshire, United Kingdom, SK10 4TG

Public contact

Dr Serban Ghiorghiu, Astrazeneca, ClinicalTrialTransparency@astrazeneca.com

Scientific contact

Dr Serban Ghiorghiu, Astrazeneca, ClinicalTrialTransparency@astrazeneca.com

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

No

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

No

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

No

Analysis stage

Final

Date of interim/final analysis

11 Apr 2012

Is this the analysis of the primary completion data?

Yes

Primary completion date

11 Apr 2012

Global end of trial reached?

Yes

Global end of trial date

05 Feb 2015

Was the trial ended prematurely?

No

Main objective of the trial

To compare the progression free survival (PFS) in patients treated with AZD8931 in combination with weekly paclitaxel versus weekly paclitaxel alone

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

19 Jun 2009

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 13

Country: Number of subjects enrolled

Brazil: 33

Country: Number of subjects enrolled

Bulgaria: 11

Country: Number of subjects enrolled

Canada: 8

Country: Number of subjects enrolled

Czech Republic: 18

Country: Number of subjects enrolled

France: 6

Country: Number of subjects enrolled

Hungary: 19

Country: Number of subjects enrolled

Italy: 6

Country: Number of subjects enrolled

Panama: 4

Country: Number of subjects enrolled

Peru: 25

Country: Number of subjects enrolled

Spain: 41

Country: Number of subjects enrolled

Sweden: 2

Country: Number of subjects enrolled

Switzerland: 3

Country: Number of subjects enrolled

United Kingdom: 21

Worldwide total number of subjects

210

EEA total number of subjects

137

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

173

From 65 to 84 years

37

85 years and over

0

Subject disposition

Top of page

Recruitment details

Phase I: 20 patients enrolled, 6 to AZD8931 160mg, 2 to AZD8931 120 mg, 6 to AZD8931 80 mg and 6 to AZD8931 40mg. Phase II: 305 enrolled, 190 randomised, 94 and 96 allocated to AZD8931 40mg + Paclitaxel and Placebo + Paclitaxel respectively. Enrolled patients differs slightly from protocol as focus was on achieving number to be randomised.

Screening details

Phase I: 20 patients enrolled, 6 to AZD8931 160mg, 2 to AZD8931 120 mg, 6 to AZD8931 80 mg and 6 to AZD8931 40mg. Phase II: 305 enrolled, 190 randomised, 94 and 96 allocated to AZD8931 40mg + Paclitaxel and Placebo + Paclitaxel respectively. Enrolled patients differs slightly from protocol as focus was on achieving number to be randomised.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Data analyst, Assessor

Blinding implementation details

Part A not blinded. Part B blinded , 1:1 randomisation

Are arms mutually exclusive

Yes

AZD8931 160 mg bd

Arm description

Part A: AZD8931 160mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Arm type

Experimental

Investigational medicinal product name

AZD8931

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

160mg bd

AZD8931 120 mg bd

Arm description

Part A: AZD8931 120mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Arm type

Experimental

Investigational medicinal product name

AZD8931

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

120mg bd

AZD8931 80 mg bd

Arm description

Part A: AZD8931 80mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Arm type

Experimental

Investigational medicinal product name

AZD8931

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

80mg bd

AZD8931 40 mg bd

Arm description

Part A: AZD8931 40mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Arm type

Experimental

Investigational medicinal product name

AZD8931

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

40mg bd

AZD8931 40MG bd + Paclitaxel

Arm description

Part B: AZD8931 40mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Arm type

Experimental

Investigational medicinal product name

AZD8931

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

AZD8931 40mg bd

Placebo + Paclitaxel

Arm description

Part B: Placebo (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

placebo to match bd

Number of subjects in period 1	AZD8931 160 mg bd	AZD8931 120 mg bd	AZD8931 80 mg bd	AZD8931 40 mg bd	AZD8931 40MG bd + Paclitaxel	Placebo + Paclitaxel
Started	6	2	6	6	94	96
Completed	0	0	0	0	65	70
Not completed	6	2	6	6	29	26
Adverse event, serious fatal	-	-	-	-	28	24
Consent withdrawn by subject	1	-	1	-	1	2
Adverse event, non-fatal	1	2	-	3	-	-
Condition under investigation worsened	4	-	5	3	-	-

Baseline characteristics

Top of page

Reporting group title

AZD8931 160 mg bd

Reporting group description

Part A: AZD8931 160mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Reporting group title

AZD8931 120 mg bd

Reporting group description

Part A: AZD8931 120mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Reporting group title

AZD8931 80 mg bd

Reporting group description

Part A: AZD8931 80mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Reporting group title

AZD8931 40 mg bd

Reporting group description

Part A: AZD8931 40mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Reporting group title

AZD8931 40MG bd + Paclitaxel

Reporting group description

Part B: AZD8931 40mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Reporting group title

Placebo + Paclitaxel

Reporting group description

Part B: Placebo (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Reporting group values	AZD8931 160 mg bd	AZD8931 120 mg bd	AZD8931 80 mg bd	AZD8931 40 mg bd	AZD8931 40MG bd + Paclitaxel	Placebo + Paclitaxel	Total
Number of subjects	6	2	6	6	94	96	210
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0
Adults (18-64 years)	5	1	6	5	72	84	173
From 65-84 years	1	1	0	1	22	12	37
85 years and over	0	0	0	0	0	0	0
Age Continuous \| Age for Part A
Units: Years
arithmetic mean (standard deviation)	52.7 ( 11.78 )	62 ( 16.97 )	47.2 ( 5.85 )	54.8 ( 11.07 )	54.5 ( 11.87 )	53.1 ( 10.64 )	-
Gender, Male/Female
Units: Participants
Female	5	2	5	4	94	96	206
Male	1	0	1	2	0	0	4
Age, Customized
Units: Subjects
18-<50 years	3	0	3	2	34	38	80
50-<=65 years	2	1	3	3	38	46	93
>65-<75 years	1	1	0	1	18	11	32
>=75 years	0	0	0	0	4	1	5
Race
Units: Subjects
American Indian or Alaska Native	0	0	0	0	2	2	4
Asian	0	0	0	0	0	1	1
Black or African American	0	0	0	0	4	1	5
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0
White	6	2	6	6	75	74	169
Other	0	0	0	0	13	18	31
Ethnicity
Units: Subjects
Hispanic or Latino	6	2	6	6	35	31	86
Native American	0	0	0	0	0	0	0
Native Alaskan / Inuit	0	0	0	0	0	0	0
Native Hawaiian / Pacific Islander	0	0	0	0	0	0	0
African	0	0	0	0	0	0	0
African-American	0	0	0	0	0	0	0
African-Caribbean	0	0	0	0	0	1	1
Asian (other than Chinese and Japanese)	0	0	0	0	0	1	1
Chinese	0	0	0	0	0	0	0
Japanese	0	0	0	0	0	0	0
Other	0	0	0	0	47	49	96
Not Applicable	0	0	0	0	12	14	26

End points

Top of page

Reporting group title

AZD8931 160 mg bd

Reporting group description

Part A: AZD8931 160mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Reporting group title

AZD8931 120 mg bd

Reporting group description

Part A: AZD8931 120mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Reporting group title

AZD8931 80 mg bd

Reporting group description

Part A: AZD8931 80mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Reporting group title

AZD8931 40 mg bd

Reporting group description

Part A: AZD8931 40mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Reporting group title

AZD8931 40MG bd + Paclitaxel

Reporting group description

Part B: AZD8931 40mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Reporting group title

Placebo + Paclitaxel

Reporting group description

Part B: Placebo (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle

Primary: Phase I: The number of dose limiting toxicities in AZD8931 in combination with weekly paclitaxel

Top of page

End point title

Phase I: The number of dose limiting toxicities in AZD8931 in combination with weekly paclitaxel ^[1] ^[2]

End point description

DLT is an AE or laboratory abnormality related to AZD8931, starting during the DLT evaluation period and meeting any of the following criteria (further detail in protocol): Symptomatic ocular surface lesion; CTCAE grade 4 haematological AE; CTCAE grade ≥3 of febrile neutropenia / neutropenia / thrombocytopenia / hyperkalaemia / hyperglycaemia / hypotension / urological toxicity / ILD / pneumonitis; QTcF interval > 500 msec, two ECGs ≥ 30 minutes apart; Symptomatic congestive cardiac failure and a drop in LVEF; Decrease in LVEF of ≥20% to below the LLN; CS rash remaining CTCAE grade ≥3 for ≥5 days despite optimal treatment; CTCAE grade ≥3 nausea, vomiting or diarrhoea, despite optimal therapy; Other CTCAE grade ≥3 toxicity which, in the opinion of the investigator, is CS and related to AZD8931; Delay to the administration of paclitaxel on D1 of Cycle 2 by ≥7 days. Patients could have more than one DLT.

End point type

Primary

End point timeframe

Weekly visits for routine safety monitoring from Day 1 to Day 28 for each participant

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: There is no analysis for the DLT data as, as per the protocol, this data was to be used to determine the maximum tolerated dose and no analysis was documented in the protocol.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per the study protocol, the assessment of maximum tolerated dose was only to be performed for part A of the study, and so DLTs were only determined in part A. As such, data is only reported for the Part B treatment groups.

End point values	AZD8931 160 mg bd	AZD8931 120 mg bd	AZD8931 80 mg bd	AZD8931 40 mg bd
Number of subjects analysed	6	2	6	6
Units: Number of Dose Limiting Toxicities
Total	2	1	2	0
Eye disorders: Keratitis	1	0	0	0
Eye disorders: Photophobia	1	0	0	0
Gastrointestinal disorders: Diarrhoea	1	1	0	0
Gastrointestinal disorders: Oesophagitis	0	0	1	0
Infections and infestations: Rash pustular	0	0	1	0

No statistical analyses for this end point

Primary: Phase II: Progression-free-survival (PFS) were analyzed in patients treated with AZD8931 in combination with weekly paclitaxel versus weekly paclitaxel alone

Top of page

End point title

Phase II: Progression-free-survival (PFS) were analyzed in patients treated with AZD8931 in combination with weekly paclitaxel versus weekly paclitaxel alone ^[3]

End point description

Time from the date of randomization until the date of objective disease progression (as per RECIST 1.1) or the date of death (by any cause in the absence of progression)

End point type

Primary

End point timeframe

Baseline and every 8 weeks, accessed up to data cut off on 11th April 2012

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per the study protocol, the analysis of ORR was only to be performed for part B of the study. As such, data is only reported for the Part B treatment groups.

End point values	AZD8931 40MG bd + Paclitaxel	Placebo + Paclitaxel
Number of subjects analysed	94	96
Units: Months
median (inter-quartile range (Q1-Q3))	8.7 (4.2 to 12.9)	9.1 (3.4 to 14.8)

PFS in AZD8931+ paclitaxel v paclitaxel alone

Statistical analysis description

Originally, 166 patients were to be randomised to observe at least 133 progression events, based on HR=0.67, 80% power, 2-sided 5% significant level and a median of 6 months for the placebo arm. After 190 patients were randomised, the analysis was performed at an similar level of maturity (70%) as originally planned (72%), after approximately 133 events.

Comparison groups

AZD8931 40MG bd + Paclitaxel v Placebo + Paclitaxel

Number of subjects included in analysis

190

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.679 ^[4]

Method

Cox Proportional Hazard model

Parameter type

Hazard ratio (HR)

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.52

Notes
[4] - Statistical significance threshold at this analysis was 5%

Secondary: Phase II: Objective tumour response rate (ORR) was compared in patients treated with AZD8931 in combination with weekly paclitaxel versus weekly paclitaxel alone

Top of page

End point title

Phase II: Objective tumour response rate (ORR) was compared in patients treated with AZD8931 in combination with weekly paclitaxel versus weekly paclitaxel alone ^[5]

End point description

The number of subjects with at least one visit response of CR or PR (Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD), A ≥ 20% increase in the sum of diameters of target lesions and an absolute increase of ≥ 5mm; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Not Evaluable (NE), All target lesion measurements are missing or >1/3 target lesion measurements are missing and sum of diameters of non-missing target lesions does not qualify for PD; Not applicable (NA), No target lesions are recorded at baseline))

End point type

Secondary

End point timeframe

Baseline and every 8 weeks, accessed up to data cut off on 11th April 2012

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As per the study protocol, the analysis of ORR was only to be performed for part B of the study. As such, data is only reported for the Part B treatment groups.

End point values	AZD8931 40MG bd + Paclitaxel	Placebo + Paclitaxel
Number of subjects analysed	88	85
Units: Participants
Total	52	35
Complete Response	11	6
Partial Response	41	29

ORR in AZD8931+ paclitaxel v paclitaxel alone

Statistical analysis description

Originally, 166 patients were to be randomised to observe at least 133 progression events, based on HR=0.67, 80% power, 2-sided 5% significant level and a median of 6 months for the placebo arm. After 190 patients were randomised, the analysis was performed at an similar level of maturity (70%) as originally planned (72%), after approximately 133 events.

Comparison groups

AZD8931 40MG bd + Paclitaxel v Placebo + Paclitaxel

Number of subjects included in analysis

173

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.026 ^[6]

Method

Logistic Regression

Parameter type

Odds ratio (OR)

Point estimate

2.02

Confidence interval

level

95%

sides

2-sided

lower limit

1.09

upper limit

3.75

Notes
[6] - Statistical significance threshold at this analysis was 5%

Adverse events

Top of page

Timeframe for reporting adverse events

AEs will be collected from time of signed informed consent throughout the treatment period and including the 30-day safety follow up period after the last dose of study treatment

Adverse event reporting additional description

In part B, SAEs considered related to study procedures should continue to be collected while patients are followed up for disease progression.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

1415

Reporting group title

AZD8931 40 mg bd

Reporting group description

NA

Reporting group title

AZD8931 80 mg bd

Reporting group description

NA

Reporting group title

AZD8931 120 mg bd

Reporting group description

NA

Reporting group title

AZD8931 160 mg bd

Reporting group description

NA

Reporting group title

AZD8931 40MG bd + Paclitaxel

Reporting group description

NA

Reporting group title

Placebo + Paclitaxel

Reporting group description

NA

Serious adverse events	AZD8931 40 mg bd	AZD8931 80 mg bd	AZD8931 120 mg bd	AZD8931 160 mg bd	AZD8931 40MG bd + Paclitaxel	Placebo + Paclitaxel
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 6 (66.67%)	2 / 6 (33.33%)	1 / 2 (50.00%)	3 / 6 (50.00%)	24 / 94 (25.53%)	14 / 95 (14.74%)
number of deaths (all causes)	0	0	1	2	28	24
number of deaths resulting from adverse events
Vascular disorders
HAEMATOMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
THROMBOSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
CATHETER SITE INFLAMMATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PYREXIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
BREAST FIBROSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
HYDROTHORAX
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
DYSPNOEA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	4 / 94 (4.26%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	2 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PLEURAL EFFUSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONITIS
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMOTHORAX
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PULMONARY EMBOLISM
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 2 (50.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
PULMONARY OEDEMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RESPIRATORY FAILURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Investigations
BODY TEMPERATURE INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
EJECTION FRACTION DECREASED
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
HUMERUS FRACTURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PUBIS FRACTURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
CARDIAC FAILURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ATRIAL FIBRILLATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MYOCARDIAL INFARCTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SUPRAVENTRICULAR TACHYCARDIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
CONVULSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VERTEBROBASILAR INSUFFICIENCY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VOCAL CORD PARALYSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
FEBRILE NEUTROPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	2 / 95 (2.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NEUTROPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PANCYTOPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Eye disorders
KERATITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
DIARRHOEA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NAUSEA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
OESOPHAGITIS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VOMITING
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DERMATITIS ACNEIFORM
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SKIN NECROSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SKIN ULCER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
RENAL FAILURE ACUTE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Musculoskeletal and connective tissue disorders
MYOPATHY
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PAIN IN EXTREMITY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
PLEURAL INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CATHETER SITE INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DEVICE RELATED INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DEVICE RELATED SEPSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
PNEUMONIA PRIMARY ATYPICAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PSEUDOMONAS INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PYELONEPHRITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RASH PUSTULAR
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SEPSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SEPTIC SHOCK
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1
Metabolism and nutrition disorders
DEHYDRATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
HYPOGLYCAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOKALAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPONATRAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	AZD8931 40 mg bd	AZD8931 80 mg bd	AZD8931 120 mg bd	AZD8931 160 mg bd	AZD8931 40MG bd + Paclitaxel	Placebo + Paclitaxel
Total subjects affected by non serious adverse events
subjects affected / exposed	6 / 6 (100.00%)	6 / 6 (100.00%)	2 / 2 (100.00%)	6 / 6 (100.00%)	93 / 94 (98.94%)	94 / 95 (98.95%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
UTERINE LEIOMYOMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
Vascular disorders
FLUSHING
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	11	5
HAEMATOMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
HAEMORRHAGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
HOT FLUSH
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	2	3
HYPERAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	2
HYPERTENSION
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)	0 / 6 (0.00%)	7 / 94 (7.45%)	3 / 95 (3.16%)
occurrences all number	0	2	0	0	24	4
HYPOTENSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	0	3
LYMPHOEDEMA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	3 / 94 (3.19%)	6 / 95 (6.32%)
occurrences all number	1	0	0	1	3	6
ORTHOSTATIC HYPOTENSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
PHLEBITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
VASCULITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
VARICOSE VEIN
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	1	0	0	0	1
General disorders and administration site conditions
ASTHENIA
subjects affected / exposed	5 / 6 (83.33%)	6 / 6 (100.00%)	2 / 2 (100.00%)	5 / 6 (83.33%)	25 / 94 (26.60%)	12 / 95 (12.63%)
occurrences all number	8	11	2	7	30	16
AXILLARY PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CATHETER SITE ERYTHEMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CATHETER SITE HAEMATOMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CATHETER SITE INFLAMMATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
CATHETER SITE PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CHEST DISCOMFORT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
CHEST PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	0	2
CHILLS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	5 / 94 (5.32%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	5	0
DISCOMFORT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
FACE OEDEMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
FATIGUE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	25 / 94 (26.60%)	25 / 95 (26.32%)
occurrences all number	0	0	0	0	40	29
FEELING COLD
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	4	0
GAIT DISTURBANCE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	1 / 94 (1.06%)	2 / 95 (2.11%)
occurrences all number	0	0	0	1	1	2
INFLUENZA LIKE ILLNESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	1	3
INFUSION SITE DISCOMFORT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
IRRITABILITY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	0	0	1	0	0
MALAISE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	2	1
MUCOSAL DRYNESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	0	0	1	0	0
MUCOSAL INFLAMMATION
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	21 / 94 (22.34%)	9 / 95 (9.47%)
occurrences all number	0	1	0	0	35	9
NODULE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
NON-CARDIAC CHEST PAIN
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	5 / 94 (5.32%)	0 / 95 (0.00%)
occurrences all number	1	0	0	0	5	0
OEDEMA
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	4 / 94 (4.26%)	3 / 95 (3.16%)
occurrences all number	0	1	0	0	4	3
OEDEMA PERIPHERAL
subjects affected / exposed	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	10 / 94 (10.64%)	11 / 95 (11.58%)
occurrences all number	2	0	0	0	13	18
PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	9 / 94 (9.57%)	4 / 95 (4.21%)
occurrences all number	0	0	0	0	16	17
PYREXIA
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	7 / 94 (7.45%)	11 / 95 (11.58%)
occurrences all number	1	2	0	0	9	11
SPINAL PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	1	1
XEROSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
Immune system disorders
DRUG HYPERSENSITIVITY
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	5 / 94 (5.32%)	3 / 95 (3.16%)
occurrences all number	1	0	0	0	5	4
HYPERSENSITIVITY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
Reproductive system and breast disorders
BREAST DISCHARGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
BREAST ENGORGEMENT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
BREAST HAEMORRHAGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
BREAST INFLAMMATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
BREAST PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	5	2
GENITAL DISCHARGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
GENITAL RASH
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	0	0	1	0	0
VAGINAL INFLAMMATION
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	1	0	0	2	0
VULVAL ULCERATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
VULVOVAGINAL BURNING SENSATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
VULVOVAGINAL PRURITUS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	1	1
Respiratory, thoracic and mediastinal disorders
BRONCHOPNEUMOPATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
BRONCHOSPASM
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
COUGH
subjects affected / exposed	2 / 6 (33.33%)	2 / 6 (33.33%)	0 / 2 (0.00%)	2 / 6 (33.33%)	12 / 94 (12.77%)	19 / 95 (20.00%)
occurrences all number	3	3	0	2	14	26
DYSPHONIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	2 / 94 (2.13%)	3 / 95 (3.16%)
occurrences all number	1	0	0	1	2	3
DYSPNOEA
subjects affected / exposed	3 / 6 (50.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)	0 / 6 (0.00%)	7 / 94 (7.45%)	8 / 95 (8.42%)
occurrences all number	5	0	1	0	10	8
DYSPNOEA EXERTIONAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	2	1
EPISTAXIS
subjects affected / exposed	2 / 6 (33.33%)	3 / 6 (50.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	19 / 94 (20.21%)	11 / 95 (11.58%)
occurrences all number	2	4	0	1	21	12
HAEMOPTYSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
HICCUPS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
HYPEROXIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
HYPOXIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
NASAL CONGESTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
NASAL DISCOMFORT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
NASAL DRYNESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	3 / 94 (3.19%)	0 / 95 (0.00%)
occurrences all number	0	0	0	1	3	0
NASAL MUCOSAL DISORDER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	1	2
NASAL OBSTRUCTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
OBSTRUCTIVE AIRWAYS DISORDER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
OROPHARYNGEAL DISCOMFORT
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	1	0	0	0	0
OROPHARYNGEAL PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	2	3
PLEURITIC PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
PNEUMOTHORAX
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
PRODUCTIVE COUGH
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
PULMONARY EMBOLISM
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	2
PULMONARY OEDEMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
RHINALGIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	4	0
SINUS CONGESTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
THROAT IRRITATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
UPPER AIRWAY OBSTRUCTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
WHEEZING
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
RHINORRHOEA
subjects affected / exposed	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	1 / 95 (1.05%)
occurrences all number	1	2	0	0	3	1
Psychiatric disorders
AFFECT LABILITY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
ANXIETY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	6 / 94 (6.38%)	11 / 95 (11.58%)
occurrences all number	0	0	0	0	6	13
APATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
BRADYPHRENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	0	0	1	0	0
CONFUSIONAL STATE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	1	1
DEPRESSED MOOD
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	4 / 95 (4.21%)
occurrences all number	0	0	0	0	4	4
DEPRESSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	4 / 95 (4.21%)
occurrences all number	0	0	0	0	2	4
INSOMNIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	12 / 94 (12.77%)	14 / 95 (14.74%)
occurrences all number	0	0	0	1	13	14
MOOD ALTERED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	1	2
NERVOUSNESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	1	2
RESTLESSNESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
SLEEP DISORDER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	1	3
BLOOD ALKALINE PHOSPHATASE INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
BLOOD BILIRUBIN INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
BLOOD CHOLESTEROL INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
BLOOD CREATININE INCREASED
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	1	0	0	0	1	1
BLOOD POTASSIUM DECREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CAPILLARY FRAGILITY TEST
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
ELECTROCARDIOGRAM CHANGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
ELECTROCARDIOGRAM QT PROLONGED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	4 / 94 (4.26%)	4 / 95 (4.21%)
occurrences all number	0	0	0	0	6	5
GAMMA-GLUTAMYLTRANSFERASE INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	2	2
HAEMOGLOBIN DECREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
LIVER FUNCTION TEST ABNORMAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
NEUTROPHIL COUNT DECREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	3	0
PULMONARY PHYSICAL EXAMINATION ABNORMAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
TRANSAMINASES INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
URINE COLOUR ABNORMAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
WEIGHT DECREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	8 / 94 (8.51%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	9	3
WEIGHT INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	0	3
WHITE BLOOD CELL COUNT DECREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	2
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	4 / 95 (4.21%)
occurrences all number	0	0	0	0	2	4
Injury, poisoning and procedural complications
ARTHROPOD BITE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
ARTHROPOD STING
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CONTUSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
ESCHAR
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
FALL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
HEAD INJURY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
INFUSION RELATED REACTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	1	6
LACERATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
LIGAMENT SPRAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	0	2
LIMB INJURY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	1	1	0
POST PROCEDURAL COMPLICATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
PROCEDURAL PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
RECALL PHENOMENON
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
RIB FRACTURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	2
SKIN INJURY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
THERMAL BURN
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	1	0	0	0	0
TOOTH FRACTURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
WOUND
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
WOUND DEHISCENCE
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	1	0	0	2	0
Cardiac disorders
ANGINA UNSTABLE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
PALPITATIONS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	1	2
PERICARDIAL EFFUSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
VENTRICULAR EXTRASYSTOLES
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
CARDIAC FAILURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
LEFT VENTRICULAR DYSFUNCTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	0	0	1	0	0
TACHYCARDIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	2	4
Nervous system disorders
AGEUSIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
AMNESIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	0	2
ANOSMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
APHASIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	2	0	0	0	0	0
APHONIA
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	0 / 95 (0.00%)
occurrences all number	0	1	0	0	3	0
ATAXIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
COGNITIVE DISORDER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	1	0	1
DIZZINESS
subjects affected / exposed	2 / 6 (33.33%)	3 / 6 (50.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	7 / 94 (7.45%)	7 / 95 (7.37%)
occurrences all number	2	3	0	1	10	10
DYSAESTHESIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	1	0	0	0	0	1
DYSARTHRIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	1	0	0	0	0	0
DYSGEUSIA
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 6 (16.67%)	9 / 94 (9.57%)	2 / 95 (2.11%)
occurrences all number	0	1	0	1	13	2
FACIAL NEURALGIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
HEADACHE
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)	0 / 6 (0.00%)	13 / 94 (13.83%)	16 / 95 (16.84%)
occurrences all number	0	2	0	0	21	18
HYPOAESTHESIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	4 / 95 (4.21%)
occurrences all number	0	0	0	0	3	4
HYPOGEUSIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
HYPOKINESIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
HYPOSMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
LETHARGY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	6 / 94 (6.38%)	4 / 95 (4.21%)
occurrences all number	0	0	0	0	7	4
MIGRAINE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
MIGRAINE WITH AURA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
MOTOR DYSFUNCTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	2
NEURALGIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	6
NEUROPATHY PERIPHERAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 6 (33.33%)	28 / 94 (29.79%)	25 / 95 (26.32%)
occurrences all number	0	0	0	3	34	27
PARAESTHESIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	13 / 94 (13.83%)	19 / 95 (20.00%)
occurrences all number	0	0	0	0	18	22
PERIPHERAL SENSORY NEUROPATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	11 / 94 (11.70%)	11 / 95 (11.58%)
occurrences all number	0	0	0	0	13	13
POLYNEUROPATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	3	1
PRESYNCOPE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	1	1
RESTLESS LEGS SYNDROME
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
SCIATICA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
TREMOR
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
DISTURBANCE IN ATTENTION
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	1	0	0	0	0	0
NEUROTOXICITY
subjects affected / exposed	0 / 6 (0.00%)	4 / 6 (66.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	5 / 94 (5.32%)	10 / 95 (10.53%)
occurrences all number	0	4	0	0	8	19
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	23 / 94 (24.47%)	10 / 95 (10.53%)
occurrences all number	0	0	0	1	34	14
GRANULOCYTOPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
LEUKOPENIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	5 / 94 (5.32%)	5 / 95 (5.26%)
occurrences all number	0	0	0	0	27	7
LYMPH NODE PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
LYMPHADENOPATHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
NEUTROPENIA
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	14 / 94 (14.89%)	39 / 95 (41.05%)
occurrences all number	0	1	0	0	42	86
Ear and labyrinth disorders
DEAFNESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
EAR DISCOMFORT
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	1	0	0	0	0	0
EAR PAIN
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	1	0	0	0	1	1
VERTIGO
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	0	3
VERTIGO POSITIONAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
TINNITUS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
Eye disorders
ASTHENOPIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
BLEPHARITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CATARACT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CONJUNCTIVAL DISORDER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	0	0	1	0	0
CONJUNCTIVITIS
subjects affected / exposed	0 / 6 (0.00%)	3 / 6 (50.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	7 / 94 (7.45%)	5 / 95 (5.26%)
occurrences all number	0	3	0	1	7	5
DRY EYE
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	3 / 6 (50.00%)	8 / 94 (8.51%)	3 / 95 (3.16%)
occurrences all number	0	1	0	4	8	3
ERYTHEMA OF EYELID
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	0	0	1	0	0
EXOPHTHALMOS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	1	0	0	0	0
EXTRAOCULAR MUSCLE PARESIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
EYE DISORDER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	1	1
EYE HAEMORRHAGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
EYE IRRITATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	4 / 94 (4.26%)	5 / 95 (5.26%)
occurrences all number	0	0	0	0	4	5
EYE PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
EYE PRURITUS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 6 (16.67%)	2 / 94 (2.13%)	3 / 95 (3.16%)
occurrences all number	0	1	0	1	2	3
EYELID OEDEMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
KERATITIS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 6 (16.67%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	0	1	0	1	1	1
LACRIMATION INCREASED
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	1 / 95 (1.05%)
occurrences all number	0	1	0	0	6	1
MACULAR DEGENERATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
MYOPIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
OCULAR HYPERAEMIA
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	3 / 95 (3.16%)
occurrences all number	0	3	0	0	3	3
OCULAR TOXICITY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
PHOTOPHOBIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	2 / 94 (2.13%)	2 / 95 (2.11%)
occurrences all number	0	0	0	2	2	2
PUNCTATE KERATITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
SCLERAL HYPERAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
VISUAL ACUITY REDUCED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
VISUAL IMPAIRMENT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	3	2
XEROPHTHALMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
VISION BLURRED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	4 / 94 (4.26%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	4	3
Gastrointestinal disorders
ABDOMINAL DISCOMFORT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
ABDOMINAL DISTENSION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
ABDOMINAL PAIN
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 6 (16.67%)	8 / 94 (8.51%)	12 / 95 (12.63%)
occurrences all number	0	1	0	1	9	17
ABDOMINAL PAIN LOWER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	3	0
ABDOMINAL PAIN UPPER
subjects affected / exposed	0 / 6 (0.00%)	4 / 6 (66.67%)	0 / 2 (0.00%)	2 / 6 (33.33%)	15 / 94 (15.96%)	7 / 95 (7.37%)
occurrences all number	0	6	0	2	20	11
ANAL FISSURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	3	1
ANAL INFLAMMATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
ANAL PRURITUS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
APHTHOUS STOMATITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	4 / 94 (4.26%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	4	1
CHAPPED LIPS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CHEILITIS
subjects affected / exposed	2 / 6 (33.33%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 6 (16.67%)	5 / 94 (5.32%)	0 / 95 (0.00%)
occurrences all number	2	1	0	1	8	0
CONSTIPATION
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	2 / 6 (33.33%)	19 / 94 (20.21%)	23 / 95 (24.21%)
occurrences all number	1	0	0	2	25	29
DENTAL CARIES
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
DIARRHOEA
subjects affected / exposed	5 / 6 (83.33%)	6 / 6 (100.00%)	2 / 2 (100.00%)	5 / 6 (83.33%)	78 / 94 (82.98%)	33 / 95 (34.74%)
occurrences all number	12	25	3	15	247	65
DRY MOUTH
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 6 (33.33%)	5 / 94 (5.32%)	1 / 95 (1.05%)
occurrences all number	1	2	0	2	5	1
DYSPEPSIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	16 / 94 (17.02%)	9 / 95 (9.47%)
occurrences all number	0	0	0	0	19	9
DYSPHAGIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	3	2
EPIGASTRIC DISCOMFORT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
GASTRIC DISORDER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
GASTRIC ULCER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
GASTRITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	5 / 94 (5.32%)	5 / 95 (5.26%)
occurrences all number	0	0	0	0	5	5
GASTROOESOPHAGEAL REFLUX DISEASE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	1	2
GINGIVAL BLEEDING
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
GINGIVITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
GLOSSITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
GLOSSODYNIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
HAEMORRHOIDS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	5 / 94 (5.32%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	5	4
HYPOAESTHESIA ORAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
INTESTINAL POLYP
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
LIP DRY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
LIP PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
MUCOUS STOOLS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
NAUSEA
subjects affected / exposed	1 / 6 (16.67%)	3 / 6 (50.00%)	1 / 2 (50.00%)	3 / 6 (50.00%)	39 / 94 (41.49%)	30 / 95 (31.58%)
occurrences all number	1	3	1	5	69	39
ODYNOPHAGIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 2 (50.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	1 / 95 (1.05%)
occurrences all number	1	0	1	0	4	1
OESOPHAGEAL PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
OESOPHAGITIS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	1	0	0	0	0
ORAL DISCOMFORT
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	1	0	0	1	0
ORAL DYSAESTHESIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	2	1
ORAL MUCOSAL BLISTERING
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
ORAL PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
ORAL TOXICITY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	2
PERIANAL ERYTHEMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	0	0	1	0	0
PROCTALGIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	3	0
RECTAL FISSURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
RECTAL HAEMORRHAGE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
STOMATITIS
subjects affected / exposed	2 / 6 (33.33%)	3 / 6 (50.00%)	1 / 2 (50.00%)	1 / 6 (16.67%)	20 / 94 (21.28%)	3 / 95 (3.16%)
occurrences all number	2	7	1	1	26	3
TOOTHACHE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	5 / 95 (5.26%)
occurrences all number	0	0	0	0	3	8
VOMITING
subjects affected / exposed	1 / 6 (16.67%)	2 / 6 (33.33%)	1 / 2 (50.00%)	2 / 6 (33.33%)	24 / 94 (25.53%)	14 / 95 (14.74%)
occurrences all number	1	2	1	3	43	27
Hepatobiliary disorders
GALLBLADDER PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
HEPATOTOXICITY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
HYPERBILIRUBINAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
Skin and subcutaneous tissue disorders
ACNE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
ALOPECIA
subjects affected / exposed	2 / 6 (33.33%)	3 / 6 (50.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	45 / 94 (47.87%)	48 / 95 (50.53%)
occurrences all number	2	3	0	0	45	49
DERMAL CYST
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
DERMATITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
DERMATITIS ACNEIFORM
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	21 / 94 (22.34%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	40	2
DERMATITIS ALLERGIC
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
DRUG ERUPTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	1	1	0
ECZEMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
ERYTHEMA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	7 / 94 (7.45%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	9	2
EXFOLIATIVE RASH
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	2	1
HEAT RASH
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
INGROWING NAIL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
INTERTRIGO
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	1	0	0	0	1	0
MADAROSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	1	1
NAIL DISCOLOURATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	4 / 94 (4.26%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	4	2
NAIL DISORDER
subjects affected / exposed	1 / 6 (16.67%)	3 / 6 (50.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	7 / 94 (7.45%)	8 / 95 (8.42%)
occurrences all number	1	4	0	0	7	8
NAIL DYSTROPHY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	3	4
NAIL PIGMENTATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
ONYCHOCLASIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
ONYCHOLYSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	4 / 94 (4.26%)	5 / 95 (5.26%)
occurrences all number	0	0	0	0	4	5
ONYCHOMADESIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)	0 / 6 (0.00%)	4 / 94 (4.26%)	0 / 95 (0.00%)
occurrences all number	0	2	0	0	5	0
PHOTOSENSITIVITY REACTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
PRURITUS
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	18 / 94 (19.15%)	6 / 95 (6.32%)
occurrences all number	1	4	0	0	19	6
PRURITUS GENERALISED
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	1	0	0	1	0
PURPURA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
RASH
subjects affected / exposed	3 / 6 (50.00%)	5 / 6 (83.33%)	1 / 2 (50.00%)	4 / 6 (66.67%)	59 / 94 (62.77%)	20 / 95 (21.05%)
occurrences all number	5	19	1	15	136	26
RASH ERYTHEMATOUS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
RASH GENERALISED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
RASH MACULAR
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
RASH MACULO-PAPULAR
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	4 / 94 (4.26%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	4	0
RASH PAPULAR
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	3	0
RASH PRURITIC
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	2
SKIN CHAPPED
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
SKIN DISORDER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
SKIN EXFOLIATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	4	0
SKIN FISSURES
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 6 (16.67%)	7 / 94 (7.45%)	1 / 95 (1.05%)
occurrences all number	0	1	0	1	7	1
SKIN HYPERPIGMENTATION
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	1 / 95 (1.05%)
occurrences all number	1	0	0	0	2	1
SKIN IRRITATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
SKIN LESION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
SKIN PLAQUE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
SKIN REACTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
SKIN STRIAE
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	1	0	0	0	0	0
SKIN TOXICITY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	3	0
SKIN ULCER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
SWELLING FACE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
TELANGIECTASIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
TOXIC SKIN ERUPTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
URTICARIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
DERMATOSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
DRY SKIN
subjects affected / exposed	1 / 6 (16.67%)	3 / 6 (50.00%)	0 / 2 (0.00%)	3 / 6 (50.00%)	32 / 94 (34.04%)	7 / 95 (7.37%)
occurrences all number	1	3	0	3	36	7
HYPERHIDROSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
Renal and urinary disorders
BLADDER PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CYSTITIS HAEMORRHAGIC
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
DYSURIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	10 / 94 (10.64%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	13	4
HAEMATURIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	4	0
POLLAKIURIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	3	0
PROTEINURIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
PYURIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
RENAL FAILURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
RENAL FAILURE ACUTE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
URINARY INCONTINENCE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	3	0
INCONTINENCE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
LEUKOCYTURIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	5 / 94 (5.32%)	4 / 95 (4.21%)
occurrences all number	0	0	0	0	6	5
Endocrine disorders
ADDISON'S DISEASE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)	0 / 6 (0.00%)	14 / 94 (14.89%)	19 / 95 (20.00%)
occurrences all number	0	2	0	0	25	26
ARTHRITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
BACK PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	13 / 94 (13.83%)	16 / 95 (16.84%)
occurrences all number	0	0	0	0	20	30
BONE PAIN
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	2 / 95 (2.11%)
occurrences all number	0	2	0	0	5	3
BURSITIS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	0 / 95 (0.00%)
occurrences all number	0	1	0	0	0	0
JOINT SWELLING
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
LIMB DISCOMFORT
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
MUSCLE CONTRACTURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
MUSCLE RIGIDITY
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
MUSCLE SPASMS
subjects affected / exposed	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	2 / 95 (2.11%)
occurrences all number	0	2	0	0	1	2
MUSCULAR WEAKNESS
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	3 / 94 (3.19%)	3 / 95 (3.16%)
occurrences all number	1	0	0	1	3	5
MUSCULOSKELETAL CHEST PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	8 / 94 (8.51%)	7 / 95 (7.37%)
occurrences all number	0	0	0	0	9	7
MUSCULOSKELETAL PAIN
subjects affected / exposed	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	6 / 94 (6.38%)	11 / 95 (11.58%)
occurrences all number	2	0	0	0	9	14
MYALGIA
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	6 / 94 (6.38%)	9 / 95 (9.47%)
occurrences all number	1	0	0	0	6	9
NECK PAIN
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	3 / 95 (3.16%)
occurrences all number	0	0	0	0	0	4
OSTEONECROSIS OF JAW
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
PAIN IN EXTREMITY
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	12 / 94 (12.77%)	16 / 95 (16.84%)
occurrences all number	1	0	0	0	19	25
PAIN IN JAW
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
PATHOLOGICAL FRACTURE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
SENSATION OF HEAVINESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	0	2
Infections and infestations
ABSCESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
BACTERIAL INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CANDIDIASIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
CELLULITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	4 / 95 (4.21%)
occurrences all number	0	0	0	0	1	4
CONJUNCTIVITIS BACTERIAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CONJUNCTIVITIS INFECTIVE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
CYSTITIS
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	9 / 94 (9.57%)	3 / 95 (3.16%)
occurrences all number	1	4	0	0	11	3
DERMATOPHYTOSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
DEVICE RELATED SEPSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
EAR INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
ERYSIPELAS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
FOLLICULITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
FURUNCLE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
GASTROENTERITIS VIRAL
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
HERPES VIRUS INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	0	4
HERPES ZOSTER
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	1	2
HORDEOLUM
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	0	2
LARYNGITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	1	1
LOCALISED INFECTION
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	0 / 95 (0.00%)
occurrences all number	1	1	0	0	3	0
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	4	1
LUNG INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
NAIL BED INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
NASOPHARYNGITIS
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	7 / 94 (7.45%)	9 / 95 (9.47%)
occurrences all number	1	0	0	0	8	12
ONYCHOMYCOSIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	2	2
ORAL CANDIDIASIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
ORAL HERPES
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	3	0
ORAL PUSTULE
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
PARONYCHIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	24 / 94 (25.53%)	5 / 95 (5.26%)
occurrences all number	0	0	0	0	30	6
PHARYNGITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	2	1
PHARYNGOTONSILLITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
RASH PUSTULAR
subjects affected / exposed	3 / 6 (50.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	14 / 94 (14.89%)	2 / 95 (2.11%)
occurrences all number	3	0	0	1	18	2
RESPIRATORY TRACT INFECTION
subjects affected / exposed	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 2 (50.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	6 / 95 (6.32%)
occurrences all number	1	0	1	0	4	9
RHINITIS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	3 / 95 (3.16%)
occurrences all number	0	1	0	0	1	3
SEPTIC SHOCK
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
SINUSITIS
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	5 / 95 (5.26%)
occurrences all number	0	1	0	0	0	6
SKIN INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
TINEA PEDIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
TOOTH INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
TRACHEITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	11 / 94 (11.70%)	11 / 95 (11.58%)
occurrences all number	0	1	0	0	11	13
URINARY TRACT INFECTION
subjects affected / exposed	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	19 / 94 (20.21%)	13 / 95 (13.68%)
occurrences all number	1	2	0	0	29	22
VAGINAL INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	1	2
VIRAL INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 6 (16.67%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	1	2	0
VULVITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
VULVOVAGINAL CANDIDIASIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	1	1
FUNGAL SKIN INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
INFLUENZA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	4 / 94 (4.26%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	4	2
SOFT TISSUE INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
STAPHYLOCOCCAL INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	2	1
TINEA INFECTION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
TONSILLITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	3	0
TOOTH ABSCESS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
URETERITIS
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
Metabolism and nutrition disorders
DEHYDRATION
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
HYPERCALCAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
HYPERCHOLESTEROLAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	0	0	0	0	1
HYPERGLYCAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	7 / 94 (7.45%)	5 / 95 (5.26%)
occurrences all number	0	0	0	0	9	13
HYPERKALAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	3 / 94 (3.19%)	2 / 95 (2.11%)
occurrences all number	0	0	0	0	11	2
HYPOGLYCAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
HYPOKALAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	7 / 94 (7.45%)	5 / 95 (5.26%)
occurrences all number	0	0	0	0	8	6
HYPOMAGNESAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	1 / 94 (1.06%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	1	0
HYPONATRAEMIA
subjects affected / exposed	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 6 (0.00%)	2 / 94 (2.13%)	0 / 95 (0.00%)
occurrences all number	0	0	0	0	2	0
DECREASED APPETITE
subjects affected / exposed	2 / 6 (33.33%)	2 / 6 (33.33%)	1 / 2 (50.00%)	2 / 6 (33.33%)	21 / 94 (22.34%)	15 / 95 (15.79%)
occurrences all number	2	3	2	3	27	17
FLUID RETENTION
subjects affected / exposed	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 6 (0.00%)	0 / 94 (0.00%)	1 / 95 (1.05%)
occurrences all number	0	1	0	0	0	1

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Were there any global substantial amendments to the protocol? No

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.

The endpoint of MTD is not statistically analysed The planned analyses of OS and PFS at 50% OS maturity were not performed AEs were coded using MedDRA v14.0 (A) and v15.0 (B) OS data was not mature enough to determine median in either group

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