Download PDF

Clinical Trial Results:
Phase III trial of combined immunochemotherapy with Fludarabine, Cyclophosphamide and Rituximab (FCR) versus Bendamustine and Rituximab (BR) in patients with previously untreated chronic lymphocytic leukemia

Summary
EudraCT number	2007-007587-21
Trial protocol	DE AT DK CZ
Global end of trial date	01 Jan 2018

Results information
Results version number	v1(current)
This version publication date	21 Aug 2020
First version publication date	21 Aug 2020
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

CLL10

ISRCTN number

US NCT number

NCT00769522

WHO universal trial number (UTN)

Sponsor organisation name

German CLL Study Group, University Hospital Cologne

Sponsor organisation address

Gleuelerstr. 176-178, Cologne, Germany, 50935

Public contact

Information Desk, German CLL Study Group, +49 22147888198, cll-studie@uk-koeln.de

Scientific contact

Information Desk, German CLL Study Group, +49 22147888198, cll-studie@uk-koeln.de

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

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

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

Analysis stage

Final

Date of interim/final analysis

12 Mar 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

29 Dec 2017

Global end of trial reached?

Yes

Global end of trial date

01 Jan 2018

Was the trial ended prematurely?

Main objective of the trial

The main objective is to demonstrate that BR has a non-inferior therapeutic efficacy compared with FCR, but a better safety profile causing less myelosuppression, infections and secondary neoplasias.

Protection of trial subjects

For a prevention of an anaphylactic reaction and a cytokine release Syndrome patients should be pretreated with antihistamines, Paracetamol/Acetaminophen and Prednisolon. In case of a leukocytopenia CTC grade 3 or 4 with a Duration of >7 days, phophylaxis of pneumocystis carinii-pneumonia is recommended. Other routine measures such as antibiotic, antimycotic or viostatic prophylaxis as well as the use of growth factors should be given if clinically indicated.

Background therapy

Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab (FCR) is the Standard therapy for physically fit patients with acvanced chronic lymphocytic leukaemia and Background therapy in the CLL10-trial. Following the results of a Phase 2 study by the MD Anderson Cancer Center and a Phase 3 Study by the German CLL-Study Group, the CLL8 study, FCR has become the Standard front-line therapy for physically fit patients with chronic lymphocytic leukemia. However this Regimen ist associated with substantial toxic effects, most importantly severe haematotoxicity in 56% of patients and severe infections in 25% of patients during treatment. A Long-term follow-up of patients treated with FCR showed prolonged neutropenia in 17-35% and an elevated risk of secondary neoplasia.

Evidence for comparator

Chemoimmunotherapy with bendamustine and rituximab (BR) is the comparator. The combination of the akylating Agent bendamustine and rituximab has shown promising results in a Phase 2 study in front-line therapy of chronic lymphocytic leukaemia with Overall responses in 103 of 117 patients and complete responses in 27 of 117 patients. Event-free survival of 34 months and low incidence of severe neutropenia (20%) and infections (8%) led to the hypothesis that the treatment with BR might be similarly effective but less toxic compared with the Standard treatment FCR.

Actual start date of recruitment

02 Oct 2008

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

6 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 10

Country: Number of subjects enrolled

Czech Republic: 4

Country: Number of subjects enrolled

Denmark: 24

Country: Number of subjects enrolled

Germany: 487

Country: Number of subjects enrolled

Switzerland: 36

Worldwide total number of subjects

561

EEA total number of subjects

525

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

353

From 65 to 84 years

208

85 years and over

Subject disposition

Top of page

Recruitment details

564 patients were enrolled between 10/2008 and 04/2012. The patients were randomly assigned to FCR (284) and BR (280) . 561 patients were allocated to treatment because 3 patients dropped off during the randomisation process. 282 patients were allocated to FCR and 279 patients were allocated to BR (baseline values).

Screening details

688 treatment-naïve patients diagnosed with CLL were registered for central screening . The central screening was performed by the GCLLSG central study office in Cologne, Germany and included immunophenotyping, FISH, evaluation of the comorbidity and renal function. 127 patients were not eligible for participation.

Number of subjects started

688 ^[1]

Number of subjects completed

561

Reason: Number of subjects

Protocol deviation: 127

Notes
[1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: All patients who meet the eligibility criteria for study entry can be enrolled into the trial. To verify the eligibility of patients, a patient screening by a medical review of the pretherapeutic staging as well as a central immunophenotyping for confirmation of the diagnosis and FISH analysis to exclude patients with a 17p deletion or mutation will be performed before randomization. 688 patients started pre-assignment period. 127 patients were assessed as Screening failures. 561 completed.

Period 1 title

overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Fludarabine/Cyclophosphamide/Rituximab

Arm description

Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab.

Arm type

Standard

Investigational medicinal product name

Fludarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Cycle 1-6 on days 1-3: 25mg/m2

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Cytoxan

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

250 mg/m2 cycle 1-6 on days 1, 2, 3.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Rituxan, Truxima

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Cycle 1: 375 mg/ m2 i.v. on day 0 Cycles 2-6: 500 mg/ m2 i.v. on day 1 (before FC)

Bendamustine/Rituximab

Arm description

Chemoimmunotherapy with bendamustine and rituximab

Arm type

Active comparator

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Ribomustin, Treanda

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

90 mg/m² course 1-6, days 1 and 2

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Rituxan, Truxima

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Cycle1: 375mg/m2 i.v. on day 0 cycles 2-6: 500 mg/m2 i.v. on day 1 (before FC)

Number of subjects in period 1	Fludarabine/Cyclophosphamide/Rituximab	Bendamustine/Rituximab
Started	282	279
treatment allocation	282	279
treatment	282	279
follow-up	282	279
Completed	199	224
Not completed	83	55
Adverse event, serious fatal	3	1
withdrawal of consent before start of treatment	3	1
Adverse event, non-fatal	65	38
various reasons	10	14
Lack of efficacy	2	1

Baseline characteristics

Top of page

Reporting group title

Fludarabine/Cyclophosphamide/Rituximab

Reporting group description

Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab.

Reporting group title

Bendamustine/Rituximab

Reporting group description

Chemoimmunotherapy with bendamustine and rituximab

Reporting group values	Fludarabine/Cyclophosphamide/Rituximab	Bendamustine/Rituximab	Total
Number of subjects	282	279	561
Age categorical
Median Age 60.5 years for FCR and 62.0 years for BR.
Units: Subjects
Adults (18-64 years)	187	166	353
65 years and over	95	113	208
Age continuous
Units: years
median (inter-quartile range (Q1-Q3))	60.5 (55 to 67)	62 (54 to 69)	-
Gender categorical
Units: Subjects
Female	81	72	153
Male	201	207	408

Subject analysis set title

CLL10 Clinical Study Report

Subject analysis set type

Intention-to-treat

Subject analysis set description

The intent-to-treat population (ITT) included all randomized subjects. 561 Patients (282 patients in the FCR arm and 279 patients in the BR arm) were assessed for progression free survival PFS (primary endpoint). PFS was measured from the date of randomization to the date of first documented disease progression (as defined by the IWCLL 2008 response criteria) or death by any cause, whichever occurred first . Following secondary endpoints were assessed: duration of Remission, event free survival (EFS), overall survival (OS), MRD, complete response rates and partial remission rates, response rates and survival times in biological subgroups, rates of toxicities and quality of life.

Subject analysis sets values	CLL10 Clinical Study Report
Number of subjects	561
Age categorical
Median Age 60.5 years for FCR and 62.0 years for BR.
Units: Subjects
Adults (18-64 years)	353
65 years and over	208
Age continuous
Units: years
median (inter-quartile range (Q1-Q3))	61 (54.5 to 68.0)
Gender categorical
Units: Subjects
Female	153
Male	408

End points

Top of page

Reporting group title

Fludarabine/Cyclophosphamide/Rituximab

Reporting group description

Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab.

Reporting group title

Bendamustine/Rituximab

Reporting group description

Chemoimmunotherapy with bendamustine and rituximab

Subject analysis set title

CLL10 Clinical Study Report

Subject analysis set type

Intention-to-treat

Subject analysis set description

Primary: Progression Free Survival (PFS)

Top of page

End point title

Progression Free Survival (PFS)

End point description

Progression free survival will be calculated as the time between date of randomization and date of progression or death of any cause.

End point type

Primary

End point timeframe

The progression free survival (PFS) rate after 24 months

End point values	Fludarabine/Cyclophosphamide/Rituximab	Bendamustine/Rituximab	CLL10 Clinical Study Report
Number of subjects analysed	282	279	561
Units: PFS rates at 24 months
number (not applicable)	84.3	77.8	81.0

Statistical plan for primary endpoint

Statistical analysis description

Progression-free survival (PFS) is defined as the time from randomization to disease progression or death from any cause. These will be counted as events for PFS. Patients who have neither progressed nor died will be censored. A Cox proportional hazard model will be applied on progression-free survival time including the variables for study medication and the stratification parameters as covariates. If the upper limit of the 90.4%-confidence interval of the hazard-ratio of BR compared to FCR is

Comparison groups

Fludarabine/Cyclophosphamide/Rituximab v Bendamustine/Rituximab

Number of subjects included in analysis

561

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

P-value

< 0.001 ^[2]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.643

Confidence interval

level

90.4%

sides

1-sided

lower limit

upper limit

2.064

Notes
[1] - The significance level of the study is 5% (one-sided, with one interim analysis and one final analysis using the method of O'Brien and Fleming to allocate the global 5% significance level to the 2 analyses), the significance level of the final analysis is accordingly 4.8%. The power is 80%. The CLL 10 protocol is a non-inferiority trial. The expected PFS 2 years after start of FCR therapy is 75% which translates to an exponential parameter of 0.1438.
[2] - A p value < 0.001 and an upper limit of the 90.4% confidence interval is greater than 1.388. Thus, the null hypothesis for the corresponding non-inferiority hypothesis cannot be rejected according to the protocol.

Adverse events

Top of page

Timeframe for reporting adverse events

Timeframe for AE

Adverse event reporting additional description

AE additional description

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Chemoimmunotherapy BR

Reporting group description

Reporting group title

Chemoimmunotherapy FCR

Reporting group description

Serious adverse events	Chemoimmunotherapy BR	Chemoimmunotherapy FCR
Total subjects affected by serious adverse events
subjects affected / exposed	135 / 278 (48.56%)	155 / 279 (55.56%)
number of deaths (all causes)	78	69
number of deaths resulting from adverse events	14	20
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
Additional description: Acute myeloid leukaemia
subjects affected / exposed	1 / 278 (0.36%)	4 / 279 (1.43%)
occurrences causally related to treatment / all	0 / 1	4 / 4
deaths causally related to treatment / all	0 / 0	3 / 3
Adenocarcinoma
Additional description: Adenocarcinoma
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Basal cell carcinoma
Additional description: Basal cell carcinoma
subjects affected / exposed	1 / 278 (0.36%)	4 / 279 (1.43%)
occurrences causally related to treatment / all	1 / 1	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Bladder cancer
Additional description: Bladder cancer
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bladder neoplasm
Additional description: Bladder neoplasm
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Breast cancer
Additional description: Breast cancer
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchial carcinoma
Additional description: Bronchial carcinoma
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Breast cancer female
Additional description: Breast cancer female
subjects affected / exposed	1 / 278 (0.36%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Clear cell sarcoma of the kidney
Additional description: Clear cell sarcoma of the kidney
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colon cancer metastatic
Additional description: Colon cancer metastatic
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colorectal cancer
Additional description: Colorectal cancer
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Glioblastoma
Additional description: Glioblastoma
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Malignant melanoma
Additional description: Malignant melanoma
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Malignant neoplasm of unknown primary site
Additional description: Malignant neoplasm of unknown primary site
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Myelodysplastic syndrome
Additional description: Myelodysplastic syndrome
subjects affected / exposed	1 / 278 (0.36%)	4 / 279 (1.43%)
occurrences causally related to treatment / all	0 / 1	4 / 5
deaths causally related to treatment / all	0 / 0	0 / 1
Metastatic neoplasm
Additional description: Metastatic neoplasm
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Oesophageal adenocarcinoma
Additional description: Oesophageal adenocarcinoma
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Prostate cancer
Additional description: Prostate cancer
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal cancer
Additional description: Rectal cancer
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Refractory anaemia with an excess of blasts
Additional description: Refractory anaemia with an excess of blasts
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin cancer
Additional description: Skin cancer
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Squamous cell carcinoma of skin
Additional description: Squamous cell carcinoma of skin
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thyroid cancer
Additional description: Thyroid cancer
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transitional cell carcinoma
Additional description: Transitional cell carcinoma
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Aortic aneurysm
Additional description: Aortic aneurysm
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Deep vein thrombosis
Additional description: Deep vein thrombosis
subjects affected / exposed	2 / 278 (0.72%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertension
Additional description: Hypertension
subjects affected / exposed	2 / 278 (0.72%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intermittent claudication
Additional description: Intermittent claudication
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral artery stenosis
Additional description: Peripheral artery stenosis
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombophlebitis
Additional description: Thrombophlebitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Hernia repair
Additional description: Hernia repair
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hip arthroplasty
Additional description: Hip arthroplasty
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hip surgery
Additional description: Hip surgery
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc operation
Additional description: Intervertebral disc operation
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Knee operation
Additional description: Knee operation
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lung lobectomy
Additional description: Lung lobectomy
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Meniscus operation
Additional description: Meniscus operation
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophagectomy
Additional description: Oesophagectomy
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Osteotomy
Additional description: Osteotomy
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Penile prosthesis insertion
Additional description: Penile prosthesis insertion
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Prostatectomy
Additional description: Prostatectomy
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal operation
Additional description: Spinal operation
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal laminectomy
Additional description: Spinal laminectomy
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal decompression
Additional description: Spinal decompression
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Thyroidectomy
Additional description: Thyroidectomy
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
Additional description: Chest pain
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Death
Additional description: Death
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	1 / 2
Pyrexia
Additional description: Pyrexia
subjects affected / exposed	17 / 278 (6.12%)	15 / 279 (5.38%)
occurrences causally related to treatment / all	14 / 17	17 / 19
deaths causally related to treatment / all	0 / 0	1 / 1
Immune system disorders
Anaphylactic reaction
Additional description: Anaphylactic reaction
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anaphylactic shock
Additional description: Anaphylactic shock
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cytokine release syndrome
Additional description: Cytokine release syndrome
subjects affected / exposed	4 / 278 (1.44%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	4 / 4	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Drug hypersensitivity
Additional description: Drug hypersensitivity
subjects affected / exposed	3 / 278 (1.08%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	2 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypersensitivity
Additional description: Hypersensitivity
subjects affected / exposed	7 / 278 (2.52%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	7 / 7	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Serum sickness
Additional description: Serum sickness
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Benign prostatic hyperplasia
Additional description: Benign prostatic hyperplasia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Calculus prostatic
Additional description: Calculus prostatic
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Prostatitis
Additional description: Prostatitis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Aspiration
Additional description: Aspiration
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Asthma
Additional description: Asthma
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchial haemorrhage
Additional description: Bronchial haemorrhage
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Chylothorax
Additional description: Chylothorax
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Epistaxis
Additional description: Epistaxis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hiccups
Additional description: Hiccups
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lung infiltration
Additional description: Lung infiltration
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural effusion
Additional description: Pleural effusion
subjects affected / exposed	1 / 278 (0.36%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonitis
Additional description: Pneumonitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax
Additional description: Pneumothorax
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
Additional description: Pulmonary embolism
subjects affected / exposed	3 / 278 (1.08%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0
Pulmonary sarcoidosis
Additional description: Pulmonary sarcoidosis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory disorder
Additional description: Respiratory disorder
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Alcoholism
Additional description: Alcoholism
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute psychosis
Additional description: Acute psychosis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Arthroscopy
Additional description: Arthroscopy
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Biopsy adrenal gland
Additional description: Biopsy adrenal gland
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood sodium decreased
Additional description: Blood sodium decreased
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigation
Additional description: Investigation
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutrophil count
Additional description: Neutrophil count
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transaminases increased
Additional description: Transaminases increased
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Allergic transfusion reaction
Additional description: Allergic transfusion reaction
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ankle fracture
Additional description: Ankle fracture
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Arterial injury
Additional description: Arterial injury
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cervical vertebral fracture
Additional description: Cervical vertebral fracture
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Fall
Additional description: Fall
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Femoral neck fracture
Additional description: Femoral neck fracture
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Foot fracture
Additional description: Foot fracture
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infusion related reaction
Additional description: Infusion related reaction
subjects affected / exposed	3 / 278 (1.08%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	4 / 4	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural haematuria
Additional description: Post procedural haematuria
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Road traffic accident
Additional description: Road traffic accident
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tendon rupture
Additional description: Tendon rupture
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transfusion reaction
Additional description: Transfusion reaction
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
Additional description: Acute coronary syndrome
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute myocardial infarction
Additional description: Acute myocardial infarction
subjects affected / exposed	3 / 278 (1.08%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	1 / 3	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Arrhythmia
Additional description: Arrhythmia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial fibrillation
Additional description: Atrial fibrillation
subjects affected / exposed	4 / 278 (1.44%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 4	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial flutter
Additional description: Atrial flutter
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial tachycardia
Additional description: Atrial tachycardia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bradyarrhythmia
Additional description: Bradyarrhythmia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure
Additional description: Cardiac failure
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery dilatation
Additional description: Coronary artery dilatation
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery disease
Additional description: Coronary artery disease
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial infarction
Additional description: Myocardial infarction
subjects affected / exposed	3 / 278 (1.08%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	1 / 3	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0
Myocardial ischaemia
Additional description: Myocardial ischaemia
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pericardial effusion
Additional description: Pericardial effusion
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tachycardia
Additional description: Tachycardia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tachyarrhythmia
Additional description: Tachyarrhythmia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Cerebellar ischaemia
Additional description: Cerebellar ischaemia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral ischaemia
Additional description: Cerebral ischaemia
subjects affected / exposed	2 / 278 (0.72%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic hyperosmolar coma
Additional description: Diabetic hyperosmolar coma
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dizziness
Additional description: Dizziness
subjects affected / exposed	0 / 278 (0.00%)	3 / 279 (1.08%)
occurrences causally related to treatment / all	0 / 0	4 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Horner's syndrome
Additional description: Horner's syndrome
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Leukoencephalopathy
Additional description: Leukoencephalopathy
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Paraesthesia
Additional description: Paraesthesia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
Additional description: Syncope
subjects affected / exposed	3 / 278 (1.08%)	3 / 279 (1.08%)
occurrences causally related to treatment / all	0 / 3	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Transient ischaemic attack
Additional description: Transient ischaemic attack
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
Additional description: Anaemia
subjects affected / exposed	0 / 278 (0.00%)	6 / 279 (2.15%)
occurrences causally related to treatment / all	0 / 0	6 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile neutropenia
Additional description: Febrile neutropenia
subjects affected / exposed	13 / 278 (4.68%)	18 / 279 (6.45%)
occurrences causally related to treatment / all	11 / 13	18 / 19
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile bone marrow aplasia
Additional description: Febrile bone marrow aplasia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemolysis
Additional description: Haemolysis
subjects affected / exposed	1 / 278 (0.36%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	1 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Haemolytic anaemia
Additional description: Haemolytic anaemia
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Leukopenia
Additional description: Leukopenia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenia
Additional description: Neutropenia
subjects affected / exposed	1 / 278 (0.36%)	4 / 279 (1.43%)
occurrences causally related to treatment / all	1 / 1	4 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Pancytopenia
Additional description: Pancytopenia
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Platelet disorder
Additional description: Platelet disorder
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenia
Additional description: Thrombocytopenia
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo positional
Additional description: Vertigo positional
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Retinal detachment
Additional description: Retinal detachment
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
Additional description: Abdominal pain
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute abdomen
Additional description: Acute abdomen
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aphthous stomatitis
Additional description: Aphthous stomatitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Constipation
Additional description: Constipation
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
Additional description: Diarrhoea
subjects affected / exposed	0 / 278 (0.00%)	3 / 279 (1.08%)
occurrences causally related to treatment / all	0 / 0	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulum
Additional description: Diverticulum
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis erosive
Additional description: Gastritis erosive
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrooesophageal reflux disease
Additional description: Gastrooesophageal reflux disease
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Inguinal hernia
Additional description: Inguinal hernia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestine perforation
Additional description: Large intestine perforation
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nausea
Additional description: Nausea
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenic colitis
Additional description: Neutropenic colitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Pancreatitis
Additional description: Pancreatitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
Additional description: Vomiting
subjects affected / exposed	2 / 278 (0.72%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	2 / 3	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
Additional description: Cholelithiasis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangiolitis
Additional description: Cholangiolitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatitis toxic
Additional description: Hepatitis toxic
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatotoxicity
Additional description: Hepatotoxicity
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis allergic
Additional description: Dermatitis allergic
subjects affected / exposed	2 / 278 (0.72%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	2 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eczema
Additional description: Eczema
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Erythema
Additional description: Erythema
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperkeratosis
Additional description: Hyperkeratosis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Leukoplakia
Additional description: Leukoplakia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rash
Additional description: Rash
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rash generalised
Additional description: Rash generalised
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Toxic epidermal necrolysis
Additional description: Toxic epidermal necrolysis
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Bladder malposition acquired
Additional description: Bladder malposition acquired
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Calculus ureteric
Additional description: Calculus ureteric
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nephrolithiasis
Additional description: Nephrolithiasis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthritis
Additional description: Arthritis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Arthrofibrosis
Additional description: Arthrofibrosis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Back pain
Additional description: Back pain
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoarthritis
Additional description: Osteoarthritis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Abscess of salivary gland
Additional description: Abscess of salivary gland
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Anal abscess
Additional description: Anal abscess
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial sepsis
Additional description: Bacterial sepsis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial infection
Additional description: Bacterial infection
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
Additional description: Bronchitis
subjects affected / exposed	3 / 278 (1.08%)	6 / 279 (2.15%)
occurrences causally related to treatment / all	0 / 4	3 / 7
deaths causally related to treatment / all	0 / 1	0 / 0
Bronchopneumonia
Additional description: Bronchopneumonia
subjects affected / exposed	3 / 278 (1.08%)	3 / 279 (1.08%)
occurrences causally related to treatment / all	1 / 3	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchopulmonary aspergillosis
Additional description: Bronchopulmonary aspergillosis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis
Additional description: Cellulitis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic sinusitis
Additional description: Chronic sinusitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Clostridium difficile sepsis
Additional description: Clostridium difficile sepsis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cystitis
Additional description: Cystitis
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulitis
Additional description: Diverticulitis
subjects affected / exposed	2 / 278 (0.72%)	3 / 279 (1.08%)
occurrences causally related to treatment / all	2 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Erysipelas
Additional description: Erysipelas
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia urinary tract infection
Additional description: Escherichia urinary tract infection
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile infection
Additional description: Febrile infection
subjects affected / exposed	3 / 278 (1.08%)	6 / 279 (2.15%)
occurrences causally related to treatment / all	3 / 3	4 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
Additional description: Gastroenteritis
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis clostridial
Additional description: Gastroenteritis clostridial
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal infection
Additional description: Gastrointestinal infection
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis norovirus
Additional description: Gastroenteritis norovirus
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Genital herpes
Additional description: Genital herpes
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
H1N1 influenza
Additional description: H1N1 influenza
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatitis B
Additional description: Hepatitis B
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Herpes zoster
Additional description: Herpes zoster
subjects affected / exposed	2 / 278 (0.72%)	9 / 279 (3.23%)
occurrences causally related to treatment / all	0 / 2	3 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster oticus
Additional description: Herpes zoster oticus
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
Additional description: Influenza
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Infection
Additional description: Infection
subjects affected / exposed	3 / 278 (1.08%)	4 / 279 (1.43%)
occurrences causally related to treatment / all	5 / 6	4 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Lung infection
Additional description: Lung infection
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenic infection
Additional description: Neutropenic infection
subjects affected / exposed	4 / 278 (1.44%)	3 / 279 (1.08%)
occurrences causally related to treatment / all	4 / 4	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenic sepsis
Additional description: Neutropenic sepsis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal candidiasis
Additional description: Oesophageal candidiasis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pharyngitis
Additional description: Pharyngitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural infection
Additional description: Pleural infection
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumocystis jirovecii pneumonia
Additional description: Pneumocystis jirovecii pneumonia
subjects affected / exposed	1 / 278 (0.36%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	1 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia bacterial
Additional description: Pneumonia bacterial
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
Additional description: Pneumonia
subjects affected / exposed	21 / 278 (7.55%)	25 / 279 (8.96%)
occurrences causally related to treatment / all	13 / 22	16 / 31
deaths causally related to treatment / all	2 / 2	1 / 2
Pneumonia haemophilus
Additional description: Pneumonia haemophilus
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia mycoplasmal
Additional description: Pneumonia mycoplasmal
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia pneumococcal
Additional description: Pneumonia pneumococcal
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia viral
Additional description: Pneumonia viral
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural sepsis
Additional description: Post procedural sepsis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Progressive multifocal leukoencephalopathy
Additional description: Progressive multifocal leukoencephalopathy
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Pulmonary sepsis
Additional description: Pulmonary sepsis
subjects affected / exposed	1 / 278 (0.36%)	3 / 279 (1.08%)
occurrences causally related to treatment / all	1 / 1	2 / 3
deaths causally related to treatment / all	0 / 0	1 / 2
Respiratory tract infection
Additional description: Respiratory tract infection
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rhinovirus infection
Additional description: Rhinovirus infection
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Scrotal abscess
Additional description: Scrotal abscess
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
Additional description: Sepsis
subjects affected / exposed	3 / 278 (1.08%)	5 / 279 (1.79%)
occurrences causally related to treatment / all	1 / 3	3 / 5
deaths causally related to treatment / all	1 / 2	2 / 2
Sinobronchitis
Additional description: Sinobronchitis
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Sinusitis
Additional description: Sinusitis
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Soft tissue infection
Additional description: Soft tissue infection
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tonsillitis
Additional description: Tonsillitis
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
Additional description: Urinary tract infection
subjects affected / exposed	2 / 278 (0.72%)	7 / 279 (2.51%)
occurrences causally related to treatment / all	2 / 2	3 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
Additional description: Upper respiratory tract infection
subjects affected / exposed	3 / 278 (1.08%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	1 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
Additional description: Urosepsis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyperglycaemia
Additional description: Hyperglycaemia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lactic acidosis
Additional description: Lactic acidosis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	Chemoimmunotherapy BR	Chemoimmunotherapy FCR
Total subjects affected by non serious adverse events
subjects affected / exposed	248 / 278 (89.21%)	271 / 279 (97.13%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
Additional description: Basal cell carcinoma
subjects affected / exposed	2 / 278 (0.72%)	2 / 279 (0.72%)
occurrences all number	2	3
Breast cancer
Additional description: Breast cancer
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Colon adenoma
Additional description: Colon adenoma
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Histiocytosis
Additional description: Histiocytosis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Oesophageal adenocarcinoma
Additional description: Oesophageal adenocarcinoma
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	2
Seborrhoeic keratosis
Additional description: Seborrhoeic keratosis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Skin cancer
Additional description: Skin cancer
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Skin papilloma
Additional description: Skin papilloma
subjects affected / exposed	2 / 278 (0.72%)	1 / 279 (0.36%)
occurrences all number	2	1
Squamous cell carcinoma of skin
Additional description: Squamous cell carcinoma of skin
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Thyroid cancer
Additional description: Thyroid cancer
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Vascular disorders
Deep vein thrombosis
Additional description: Deep vein thrombosis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Haemorrhage
Additional description: Haemorrhage
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Hot flush
Additional description: Hot flush
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Hypertension
Additional description: Hypertension
subjects affected / exposed	4 / 278 (1.44%)	2 / 279 (0.72%)
occurrences all number	4	3
Hypotension
Additional description: Hypotension
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences all number	2	0
Labile blood pressure
Additional description: Labile blood pressure
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Peripheral ischaemia
Additional description: Peripheral ischaemia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Phlebitis
Additional description: Phlebitis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Post thrombotic syndrome
Additional description: Post thrombotic syndrome
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	3
Thrombosis
Additional description: Thrombosis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Thrombophlebitis
Additional description: Thrombophlebitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Varicose vein
Additional description: Varicose vein
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Venous thrombosis limb
Additional description: Venous thrombosis limb
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Surgical and medical procedures
Catheter management
Additional description: Catheter management
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Cervical conisation
Additional description: Cervical conisation
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Haemorrhoid operation
Additional description: Haemorrhoid operation
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Hysterectomy
Additional description: Hysterectomy
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Immunoglobulin therapy
Additional description: Immunoglobulin therapy
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Papilloma excision
Additional description: Papilloma excision
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Shoulder operation
Additional description: Shoulder operation
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Skin neoplasm excision
Additional description: Skin neoplasm excision
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
General disorders and administration site conditions
Asthenia
Additional description: Asthenia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Chest pain
Additional description: Chest pain
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Chills
Additional description: Chills
subjects affected / exposed	4 / 278 (1.44%)	1 / 279 (0.36%)
occurrences all number	4	1
Fatigue
Additional description: Fatigue
subjects affected / exposed	6 / 278 (2.16%)	8 / 279 (2.87%)
occurrences all number	8	16
Generalised oedema
Additional description: Generalised oedema
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Inflammation
Additional description: Inflammation
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Influenza like illness
Additional description: Influenza like illness
subjects affected / exposed	2 / 278 (0.72%)	3 / 279 (1.08%)
occurrences all number	2	5
Mucosal inflammation
Additional description: Mucosal inflammation
subjects affected / exposed	3 / 278 (1.08%)	2 / 279 (0.72%)
occurrences all number	3	2
Oedema
Additional description: Oedema
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Pain
Additional description: Pain
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences all number	2	0
Peripheral swelling
Additional description: Peripheral swelling
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Pyrexia
Additional description: Pyrexia
subjects affected / exposed	38 / 278 (13.67%)	42 / 279 (15.05%)
occurrences all number	45	57
Ulcer
Additional description: Ulcer
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Immune system disorders
Anaphylactic reaction
Additional description: Anaphylactic reaction
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Cytokine release syndrome
Additional description: Cytokine release syndrome
subjects affected / exposed	3 / 278 (1.08%)	1 / 279 (0.36%)
occurrences all number	3	1
Drug hypersensitivity
Additional description: Drug hypersensitivity
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Hypersensitivity
Additional description: Hypersensitivity
subjects affected / exposed	17 / 278 (6.12%)	10 / 279 (3.58%)
occurrences all number	19	10
Hypogammaglobulinaemia
Additional description: Hypogammaglobulinaemia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	4	0
Type IV hypersensitivity reaction
Additional description: Type IV hypersensitivity reaction
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Reproductive system and breast disorders
Benign prostatic hyperplasia
Additional description: Benign prostatic hyperplasia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Erectile dysfunction
Additional description: Erectile dysfunction
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	7	0
Prostatitis
Additional description: Prostatitis
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Testicular pain
Additional description: Testicular pain
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Vaginal discharge
Additional description: Vaginal discharge
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Vulvovaginal dryness
Additional description: Vulvovaginal dryness
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Respiratory, thoracic and mediastinal disorders
Allergic bronchitis
Additional description: Allergic bronchitis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Bronchitis chronic
Additional description: Bronchitis chronic
subjects affected / exposed	2 / 278 (0.72%)	1 / 279 (0.36%)
occurrences all number	2	1
Bronchospasm
Additional description: Bronchospasm
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Chronic obstructive pulmonary disease
Additional description: Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	2
Chylothorax
Additional description: Chylothorax
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Cough
Additional description: Cough
subjects affected / exposed	10 / 278 (3.60%)	18 / 279 (6.45%)
occurrences all number	11	25
Cough decreased
Additional description: Cough decreased
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Dyspnoea
Additional description: Dyspnoea
subjects affected / exposed	3 / 278 (1.08%)	4 / 279 (1.43%)
occurrences all number	11	7
Dyspnoea exertional
Additional description: Dyspnoea exertional
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Epistaxis
Additional description: Epistaxis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	2	0
Oropharyngeal pain
Additional description: Oropharyngeal pain
subjects affected / exposed	2 / 278 (0.72%)	1 / 279 (0.36%)
occurrences all number	2	1
Pleural effusion
Additional description: Pleural effusion
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	2
Productive cough
Additional description: Productive cough
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Rhinitis allergic
Additional description: Rhinitis allergic
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Rhinitis atrophic
Additional description: Rhinitis atrophic
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Rhinorrhoea
Additional description: Rhinorrhoea
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	3
Psychiatric disorders
Depression
Additional description: Depression
subjects affected / exposed	4 / 278 (1.44%)	2 / 279 (0.72%)
occurrences all number	6	2
Insomnia
Additional description: Insomnia
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	4	2
Schizophrenia
Additional description: Schizophrenia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Investigations
Alanine aminotransferase
Additional description: Alanine aminotransferase
subjects affected / exposed	0 / 278 (0.00%)	3 / 279 (1.08%)
occurrences all number	0	5
Alanine aminotransferase increased
Additional description: Alanine aminotransferase increased
subjects affected / exposed	0 / 278 (0.00%)	3 / 279 (1.08%)
occurrences all number	0	4
Aspartate aminotransferase
Additional description: Aspartate aminotransferase
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	4
Aspartate aminotransferase increased
Additional description: Aspartate aminotransferase increased
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	2
Blood creatinine increased
Additional description: Blood creatinine increased
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Blood creatinine
Additional description: Blood creatinine
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Blood bilirubin
Additional description: Blood bilirubin
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Blood alkaline phosphatase increased
Additional description: Blood alkaline phosphatase increased
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Blood lactate dehydrogenase increased
Additional description: Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Body temperature increased
Additional description: Body temperature increased
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Blood potassium decreased
Additional description: Blood potassium decreased
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	2
C-reactive protein increased
Additional description: C-reactive protein increased
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences all number	2	0
CD4 lymphocytes
Additional description: CD4 lymphocytes
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	2	0
CD4 lymphocytes decreased
Additional description: CD4 lymphocytes decreased
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	9
Gamma-glutamyltransferase increased
Additional description: Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 278 (0.00%)	3 / 279 (1.08%)
occurrences all number	0	4
Gamma-glutamyltransferase
Additional description: Gamma-glutamyltransferase
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	11
Haemoglobin
Additional description: Haemoglobin
subjects affected / exposed	9 / 278 (3.24%)	10 / 279 (3.58%)
occurrences all number	17	35
Granulocytes abnormal
Additional description: Granulocytes abnormal
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	5
Haemoglobin decreased
Additional description: Haemoglobin decreased
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	3
Hepatitis B antibody positive
Additional description: Hepatitis B antibody positive
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Hepatic enzyme increased
Additional description: Hepatic enzyme increased
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	2
Immunoglobulins decreased
Additional description: Immunoglobulins decreased
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	3	1
Intraocular pressure increased
Additional description: Intraocular pressure increased
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Lipase
Additional description: Lipase
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Neutrophil count
Additional description: Neutrophil count
subjects affected / exposed	20 / 278 (7.19%)	33 / 279 (11.83%)
occurrences all number	41	89
Neutrophil count decreased
Additional description: Neutrophil count decreased
subjects affected / exposed	1 / 278 (0.36%)	3 / 279 (1.08%)
occurrences all number	2	3
Platelet count
Additional description: Platelet count
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	2
Platelet count decreased
Additional description: Platelet count decreased
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	2	0
Prothrombin time shortened
Additional description: Prothrombin time shortened
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Transaminases increased
Additional description: Transaminases increased
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
White blood cell count
Additional description: White blood cell count
subjects affected / exposed	15 / 278 (5.40%)	26 / 279 (9.32%)
occurrences all number	38	92
Weight decreased
Additional description: Weight decreased
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Injury, poisoning and procedural complications
Arterial injury
Additional description: Arterial injury
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	8
Foot fracture
Additional description: Foot fracture
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Infusion related reaction
Additional description: Infusion related reaction
subjects affected / exposed	2 / 278 (0.72%)	3 / 279 (1.08%)
occurrences all number	2	3
Meniscus injury
Additional description: Meniscus injury
subjects affected / exposed	2 / 278 (0.72%)	1 / 279 (0.36%)
occurrences all number	2	1
Postoperative fever
Additional description: Postoperative fever
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Skull fracture
Additional description: Skull fracture
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Wound
Additional description: Wound
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Cardiac disorders
Angina pectoris
Additional description: Angina pectoris
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Arrhythmia
Additional description: Arrhythmia
subjects affected / exposed	3 / 278 (1.08%)	1 / 279 (0.36%)
occurrences all number	3	1
Atrial fibrillation
Additional description: Atrial fibrillation
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Cardiac failure
Additional description: Cardiac failure
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Myocardial ischaemia
Additional description: Myocardial ischaemia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Tachycardia
Additional description: Tachycardia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	2	0
Tachyarrhythmia
Additional description: Tachyarrhythmia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Nervous system disorders
Carotid artery stenosis
Additional description: Carotid artery stenosis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Carpal tunnel syndrome
Additional description: Carpal tunnel syndrome
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	4
Cervicogenic headache
Additional description: Cervicogenic headache
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Depressed level of consciousness
Additional description: Depressed level of consciousness
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Dizziness
Additional description: Dizziness
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	2
Dystonia
Additional description: Dystonia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Headache
Additional description: Headache
subjects affected / exposed	3 / 278 (1.08%)	0 / 279 (0.00%)
occurrences all number	3	0
Hypoaesthesia
Additional description: Hypoaesthesia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Monoparesis
Additional description: Monoparesis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Migraine with aura
Additional description: Migraine with aura
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Memory impairment
Additional description: Memory impairment
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Neuralgia
Additional description: Neuralgia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Paraesthesia
Additional description: Paraesthesia
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	2
Paresis cranial nerve
Additional description: Paresis cranial nerve
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Parkinson's disease
Additional description: Parkinson's disease
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Peripheral sensory neuropathy
Additional description: Peripheral sensory neuropathy
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Polyneuropathy
Additional description: Polyneuropathy
subjects affected / exposed	3 / 278 (1.08%)	2 / 279 (0.72%)
occurrences all number	10	2
Post herpetic neuralgia
Additional description: Post herpetic neuralgia
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	5
Restless legs syndrome
Additional description: Restless legs syndrome
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Syncope
Additional description: Syncope
subjects affected / exposed	3 / 278 (1.08%)	0 / 279 (0.00%)
occurrences all number	3	0
Transient ischaemic attack
Additional description: Transient ischaemic attack
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Blood and lymphatic system disorders
Anaemia vitamin B12 deficiency
Additional description: Anaemia vitamin B12 deficiency
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Anaemia folate deficiency
Additional description: Anaemia folate deficiency
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Anaemia
Additional description: Anaemia
subjects affected / exposed	18 / 278 (6.47%)	26 / 279 (9.32%)
occurrences all number	30	39
Autoimmune haemolytic anaemia
Additional description: Autoimmune haemolytic anaemia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Febrile neutropenia
Additional description: Febrile neutropenia
subjects affected / exposed	4 / 278 (1.44%)	4 / 279 (1.43%)
occurrences all number	6	4
Granulocytopenia
Additional description: Granulocytopenia
subjects affected / exposed	3 / 278 (1.08%)	3 / 279 (1.08%)
occurrences all number	4	3
Haemolytic anaemia
Additional description: Haemolytic anaemia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Haemolysis
Additional description: Haemolysis
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	2	1
Leukopenia
Additional description: Leukopenia
subjects affected / exposed	127 / 278 (45.68%)	208 / 279 (74.55%)
occurrences all number	321	818
Neutropenia
Additional description: Neutropenia
subjects affected / exposed	153 / 278 (55.04%)	216 / 279 (77.42%)
occurrences all number	369	802
Pancytopenia
Additional description: Pancytopenia
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	3
Platelet disorder
Additional description: Platelet disorder
subjects affected / exposed	5 / 278 (1.80%)	8 / 279 (2.87%)
occurrences all number	6	22
Thrombocytopenia
Additional description: Thrombocytopenia
subjects affected / exposed	45 / 278 (16.19%)	61 / 279 (21.86%)
occurrences all number	86	138
Ear and labyrinth disorders
Deafness
Additional description: Deafness
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Hearing impaired
Additional description: Hearing impaired
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Tinnitus
Additional description: Tinnitus
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Vestibular disorder
Additional description: Vestibular disorder
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	2
Vertigo
Additional description: Vertigo
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Eye disorders
Age-related macular degeneration
Additional description: Age-related macular degeneration
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Glaucoma
Additional description: Glaucoma
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	2	0
Lacrimation increased
Additional description: Lacrimation increased
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Visual impairment
Additional description: Visual impairment
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences all number	3	0
Gastrointestinal disorders
Abdominal distension
Additional description: Abdominal distension
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Abdominal pain upper
Additional description: Abdominal pain upper
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences all number	2	0
Abdominal pain
Additional description: Abdominal pain
subjects affected / exposed	1 / 278 (0.36%)	3 / 279 (1.08%)
occurrences all number	1	3
Anal fissure
Additional description: Anal fissure
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Anal prolapse
Additional description: Anal prolapse
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	2	0
Anal ulcer
Additional description: Anal ulcer
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Aphthous stomatitis
Additional description: Aphthous stomatitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Chronic gastritis
Additional description: Chronic gastritis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Colitis
Additional description: Colitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Constipation
Additional description: Constipation
subjects affected / exposed	1 / 278 (0.36%)	2 / 279 (0.72%)
occurrences all number	1	2
Diarrhoea
Additional description: Diarrhoea
subjects affected / exposed	2 / 278 (0.72%)	4 / 279 (1.43%)
occurrences all number	2	6
Dyspepsia
Additional description: Dyspepsia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Enteritis
Additional description: Enteritis
subjects affected / exposed	1 / 278 (0.36%)	2 / 279 (0.72%)
occurrences all number	1	2
Enterocolitis
Additional description: Enterocolitis
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	2
Gastric ulcer
Additional description: Gastric ulcer
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Gastritis
Additional description: Gastritis
subjects affected / exposed	3 / 278 (1.08%)	0 / 279 (0.00%)
occurrences all number	5	0
Gastrooesophageal reflux disease
Additional description: Gastrooesophageal reflux disease
subjects affected / exposed	3 / 278 (1.08%)	0 / 279 (0.00%)
occurrences all number	4	0
Haemorrhoids
Additional description: Haemorrhoids
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Ileus
Additional description: Ileus
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Inguinal hernia
Additional description: Inguinal hernia
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Nausea
Additional description: Nausea
subjects affected / exposed	7 / 278 (2.52%)	5 / 279 (1.79%)
occurrences all number	7	8
Oral mucosal discolouration
Additional description: Oral mucosal discolouration
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Periodontal inflammation
Additional description: Periodontal inflammation
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Stomatitis
Additional description: Stomatitis
subjects affected / exposed	0 / 278 (0.00%)	4 / 279 (1.43%)
occurrences all number	0	4
Toothache
Additional description: Toothache
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Tooth loss
Additional description: Tooth loss
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Vomiting
Additional description: Vomiting
subjects affected / exposed	5 / 278 (1.80%)	4 / 279 (1.43%)
occurrences all number	5	6
Hepatobiliary disorders
Cholelithiasis
Additional description: Cholelithiasis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Hepatitis alcoholic
Additional description: Hepatitis alcoholic
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	2
Hyperbilirubinaemia
Additional description: Hyperbilirubinaemia
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	2
Skin and subcutaneous tissue disorders
Acne
Additional description: Acne
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Actinic keratosis
Additional description: Actinic keratosis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Blister
Additional description: Blister
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Dermatitis allergic
Additional description: Dermatitis allergic
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Dermatitis psoriasiform
Additional description: Dermatitis psoriasiform
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Dry skin
Additional description: Dry skin
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Eczema
Additional description: Eczema
subjects affected / exposed	2 / 278 (0.72%)	2 / 279 (0.72%)
occurrences all number	3	2
Erythema
Additional description: Erythema
subjects affected / exposed	3 / 278 (1.08%)	5 / 279 (1.79%)
occurrences all number	4	10
Erythema nodosum
Additional description: Erythema nodosum
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Erythema multiforme
Additional description: Erythema multiforme
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Hyperhidrosis
Additional description: Hyperhidrosis
subjects affected / exposed	0 / 278 (0.00%)	4 / 279 (1.43%)
occurrences all number	0	6
Hyperkeratosis
Additional description: Hyperkeratosis
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences all number	4	0
Neurodermatitis
Additional description: Neurodermatitis
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	11
Petechiae
Additional description: Petechiae
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Photosensitivity reaction
Additional description: Photosensitivity reaction
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Pruritus
Additional description: Pruritus
subjects affected / exposed	11 / 278 (3.96%)	8 / 279 (2.87%)
occurrences all number	16	12
Psoriasis
Additional description: Psoriasis
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Rash
Additional description: Rash
subjects affected / exposed	16 / 278 (5.76%)	16 / 279 (5.73%)
occurrences all number	30	18
Rash generalised
Additional description: Rash generalised
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Rash maculo-papular
Additional description: Rash maculo-papular
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	6
Rash pruritic
Additional description: Rash pruritic
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Rash papular
Additional description: Rash papular
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Skin exfoliation
Additional description: Skin exfoliation
subjects affected / exposed	5 / 278 (1.80%)	0 / 279 (0.00%)
occurrences all number	7	0
Skin lesion
Additional description: Skin lesion
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences all number	2	0
Skin texture abnormal
Additional description: Skin texture abnormal
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Skin ulcer
Additional description: Skin ulcer
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	4
Urticaria
Additional description: Urticaria
subjects affected / exposed	5 / 278 (1.80%)	1 / 279 (0.36%)
occurrences all number	7	1
Renal and urinary disorders
Cystitis noninfective
Additional description: Cystitis noninfective
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Dysuria
Additional description: Dysuria
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Pollakiuria
Additional description: Pollakiuria
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Renal colic
Additional description: Renal colic
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Renal failure
Additional description: Renal failure
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Stress urinary incontinence
Additional description: Stress urinary incontinence
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Endocrine disorders
Autoimmune thyroiditis
Additional description: Autoimmune thyroiditis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Hyperthyroidism
Additional description: Hyperthyroidism
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	2
Musculoskeletal and connective tissue disorders
Arthralgia
Additional description: Arthralgia
subjects affected / exposed	3 / 278 (1.08%)	4 / 279 (1.43%)
occurrences all number	6	9
Arthritis
Additional description: Arthritis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Arthrofibrosis
Additional description: Arthrofibrosis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Back pain
Additional description: Back pain
subjects affected / exposed	3 / 278 (1.08%)	4 / 279 (1.43%)
occurrences all number	6	6
Intervertebral disc protrusion
Additional description: Intervertebral disc protrusion
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Musculoskeletal pain
Additional description: Musculoskeletal pain
subjects affected / exposed	3 / 278 (1.08%)	0 / 279 (0.00%)
occurrences all number	5	0
Muscle spasms
Additional description: Muscle spasms
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Neck pain
Additional description: Neck pain
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Osteoarthritis
Additional description: Osteoarthritis
subjects affected / exposed	3 / 278 (1.08%)	2 / 279 (0.72%)
occurrences all number	5	6
Osteopenia
Additional description: Osteopenia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Osteoporosis
Additional description: Osteoporosis
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	2
Pain in extremity
Additional description: Pain in extremity
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Periarthritis
Additional description: Periarthritis
subjects affected / exposed	2 / 278 (0.72%)	0 / 279 (0.00%)
occurrences all number	3	0
Polyarthritis
Additional description: Polyarthritis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	2	0
Polymyalgia rheumatica
Additional description: Polymyalgia rheumatica
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	3	0
Rheumatoid arthritis
Additional description: Rheumatoid arthritis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	6	0
Scoliosis
Additional description: Scoliosis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Rotator cuff syndrome
Additional description: Rotator cuff syndrome
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	2
Seronegative arthritis
Additional description: Seronegative arthritis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	3	0
Spinal osteoarthritis
Additional description: Spinal osteoarthritis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Infections and infestations
Abscess
Additional description: Abscess
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Abscess jaw
Additional description: Abscess jaw
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Acute tonsillitis
Additional description: Acute tonsillitis
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Aspergillus infection
Additional description: Aspergillus infection
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Bacteraemia
Additional description: Bacteraemia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Bronchitis
Additional description: Bronchitis
subjects affected / exposed	31 / 278 (11.15%)	30 / 279 (10.75%)
occurrences all number	44	47
Bronchopneumonia
Additional description: Bronchopneumonia
subjects affected / exposed	2 / 278 (0.72%)	3 / 279 (1.08%)
occurrences all number	2	5
Campylobacter gastroenteritis
Additional description: Campylobacter gastroenteritis
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Candida infection
Additional description: Candida infection
subjects affected / exposed	2 / 278 (0.72%)	1 / 279 (0.36%)
occurrences all number	2	2
Chronic sinusitis
Additional description: Chronic sinusitis
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	2
Conjunctivitis
Additional description: Conjunctivitis
subjects affected / exposed	3 / 278 (1.08%)	2 / 279 (0.72%)
occurrences all number	3	2
Cytomegalovirus infection
Additional description: Cytomegalovirus infection
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	2
Cystitis
Additional description: Cystitis
subjects affected / exposed	2 / 278 (0.72%)	3 / 279 (1.08%)
occurrences all number	2	5
Diverticulitis
Additional description: Diverticulitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Dysentery
Additional description: Dysentery
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Ear infection
Additional description: Ear infection
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Erysipelas
Additional description: Erysipelas
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Erythema migrans
Additional description: Erythema migrans
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Febrile infection
Additional description: Febrile infection
subjects affected / exposed	7 / 278 (2.52%)	7 / 279 (2.51%)
occurrences all number	7	7
Fungal infection
Additional description: Fungal infection
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Fungal skin infection
Additional description: Fungal skin infection
subjects affected / exposed	1 / 278 (0.36%)	2 / 279 (0.72%)
occurrences all number	1	2
Furuncle
Additional description: Furuncle
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Gastroenteritis
Additional description: Gastroenteritis
subjects affected / exposed	2 / 278 (0.72%)	3 / 279 (1.08%)
occurrences all number	2	3
Gastrointestinal infection
Additional description: Gastrointestinal infection
subjects affected / exposed	3 / 278 (1.08%)	3 / 279 (1.08%)
occurrences all number	3	3
Gastroenteritis norovirus
Additional description: Gastroenteritis norovirus
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Gingivitis
Additional description: Gingivitis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Genital infection fungal
Additional description: Genital infection fungal
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
H1N1 influenza
Additional description: H1N1 influenza
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Hepatitis E
Additional description: Hepatitis E
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Herpes zoster
Additional description: Herpes zoster
subjects affected / exposed	16 / 278 (5.76%)	31 / 279 (11.11%)
occurrences all number	19	34
Herpes virus infection
Additional description: Herpes virus infection
subjects affected / exposed	5 / 278 (1.80%)	9 / 279 (3.23%)
occurrences all number	6	12
Herpes simplex
Additional description: Herpes simplex
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Infection susceptibility increased
Additional description: Infection susceptibility increased
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Infection
Additional description: Infection
subjects affected / exposed	18 / 278 (6.47%)	12 / 279 (4.30%)
occurrences all number	20	12
Infected varicose vein
Additional description: Infected varicose vein
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Infected bites
Additional description: Infected bites
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Influenza
Additional description: Influenza
subjects affected / exposed	10 / 278 (3.60%)	5 / 279 (1.79%)
occurrences all number	11	5
Laryngitis
Additional description: Laryngitis
subjects affected / exposed	2 / 278 (0.72%)	1 / 279 (0.36%)
occurrences all number	2	1
Laryngitis bacterial
Additional description: Laryngitis bacterial
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Localised infection
Additional description: Localised infection
subjects affected / exposed	4 / 278 (1.44%)	2 / 279 (0.72%)
occurrences all number	4	2
Lung infection
Additional description: Lung infection
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Lyme disease
Additional description: Lyme disease
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Mastitis
Additional description: Mastitis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Nasopharyngitis
Additional description: Nasopharyngitis
subjects affected / exposed	52 / 278 (18.71%)	52 / 279 (18.64%)
occurrences all number	67	72
Muscle abscess
Additional description: Muscle abscess
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	2
Oesophageal candidiasis
Additional description: Oesophageal candidiasis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Ophthalmic herpes zoster
Additional description: Ophthalmic herpes zoster
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Oral fungal infection
Additional description: Oral fungal infection
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Oral infection
Additional description: Oral infection
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Oral herpes
Additional description: Oral herpes
subjects affected / exposed	17 / 278 (6.12%)	17 / 279 (6.09%)
occurrences all number	23	19
Otitis media
Additional description: Otitis media
subjects affected / exposed	2 / 278 (0.72%)	3 / 279 (1.08%)
occurrences all number	2	3
Pharyngitis
Additional description: Pharyngitis
subjects affected / exposed	9 / 278 (3.24%)	5 / 279 (1.79%)
occurrences all number	9	5
Pharyngeal chlamydia infection
Additional description: Pharyngeal chlamydia infection
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Pneumocystis jirovecii pneumonia
Additional description: Pneumocystis jirovecii pneumonia
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Pneumonia
Additional description: Pneumonia
subjects affected / exposed	13 / 278 (4.68%)	16 / 279 (5.73%)
occurrences all number	17	16
Postoperative wound infection
Additional description: Postoperative wound infection
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Pulmonary mycosis
Additional description: Pulmonary mycosis
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Pyelonephritis
Additional description: Pyelonephritis
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Respiratory tract infection
Additional description: Respiratory tract infection
subjects affected / exposed	6 / 278 (2.16%)	15 / 279 (5.38%)
occurrences all number	7	21
Rhinitis
Additional description: Rhinitis
subjects affected / exposed	5 / 278 (1.80%)	6 / 279 (2.15%)
occurrences all number	5	7
Sinobronchitis
Additional description: Sinobronchitis
subjects affected / exposed	1 / 278 (0.36%)	2 / 279 (0.72%)
occurrences all number	1	3
Sinusitis
Additional description: Sinusitis
subjects affected / exposed	10 / 278 (3.60%)	19 / 279 (6.81%)
occurrences all number	13	28
Skin bacterial infection
Additional description: Skin bacterial infection
subjects affected / exposed	1 / 278 (0.36%)	2 / 279 (0.72%)
occurrences all number	1	2
Skin infection
Additional description: Skin infection
subjects affected / exposed	1 / 278 (0.36%)	3 / 279 (1.08%)
occurrences all number	1	3
Staphylococcal infection
Additional description: Staphylococcal infection
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Tooth abscess
Additional description: Tooth abscess
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	2
Tooth infection
Additional description: Tooth infection
subjects affected / exposed	2 / 278 (0.72%)	3 / 279 (1.08%)
occurrences all number	2	3
Tonsillitis
Additional description: Tonsillitis
subjects affected / exposed	3 / 278 (1.08%)	3 / 279 (1.08%)
occurrences all number	3	3
Tracheobronchitis
Additional description: Tracheobronchitis
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	2
Vaginal infection
Additional description: Vaginal infection
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Urinary tract infection
Additional description: Urinary tract infection
subjects affected / exposed	16 / 278 (5.76%)	12 / 279 (4.30%)
occurrences all number	18	23
Upper respiratory tract infection
Additional description: Upper respiratory tract infection
subjects affected / exposed	25 / 278 (8.99%)	50 / 279 (17.92%)
occurrences all number	32	75
Vaccination site infection
Additional description: Vaccination site infection
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Varicella
Additional description: Varicella
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Viral infection
Additional description: Viral infection
subjects affected / exposed	4 / 278 (1.44%)	5 / 279 (1.79%)
occurrences all number	4	5
Wound infection
Additional description: Wound infection
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Metabolism and nutrition disorders
Decreased appetite
Additional description: Decreased appetite
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	1
Folate deficiency
Additional description: Folate deficiency
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	6
Gout
Additional description: Gout
subjects affected / exposed	1 / 278 (0.36%)	0 / 279 (0.00%)
occurrences all number	1	0
Hypercholesterolaemia
Additional description: Hypercholesterolaemia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Hyperglycaemia
Additional description: Hyperglycaemia
subjects affected / exposed	0 / 278 (0.00%)	2 / 279 (0.72%)
occurrences all number	0	3
Hyperkalaemia
Additional description: Hyperkalaemia
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	1
Iron overload
Additional description: Iron overload
subjects affected / exposed	0 / 278 (0.00%)	1 / 279 (0.36%)
occurrences all number	0	2
Vitamin B12 deficiency
Additional description: Vitamin B12 deficiency
subjects affected / exposed	1 / 278 (0.36%)	1 / 279 (0.36%)
occurrences all number	1	6

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

25 Jun 2010

Global Amendment with German Protocol version 3.1 and date 25.06.2010 was submitted separately in each Country.

Were there any global interruptions to the trial? No

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

None reported

http://www.ncbi.nlm.nih.gov/pubmed/27216274

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

Clinical trials

Clinical Trial Results:
Phase III trial of combined immunochemotherapy with Fludarabine, Cyclophosphamide and Rituximab (FCR) versus Bendamustine and Rituximab (BR) in patients with previously untreated chronic lymphocytic leukemia

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Progression Free Survival (PFS)

Primary: Progression Free Survival (PFS)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

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

Clinical trials

Clinical Trial Results: Phase III trial of combined immunochemotherapy with Fludarabine, Cyclophosphamide and Rituximab (FCR) versus Bendamustine and Rituximab (BR) in patients with previously untreated chronic lymphocytic leukemia

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Progression Free Survival (PFS)

Primary: Progression Free Survival (PFS)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
Phase III trial of combined immunochemotherapy with Fludarabine, Cyclophosphamide and Rituximab (FCR) versus Bendamustine and Rituximab (BR) in patients with previously untreated chronic lymphocytic leukemia