Clinical Trial Results:
Title: An Open-Label Phase 2 Study of Tipifarnib in Subjects with Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL) Study design: This study utilised an open-label, nonrandomised design, a standard and appropriate approach for a Phase 2 study in subjects with relapsed or refractory PTCL. The primary objective was to determine the antitumour activity in terms of objective response rate (ORR) of tipifarnib in subjects with relapsed or refractory PTCL. Secondary objectives included antitumor activity in terms of progression-free survival (PFS) and duration of response (DOR), the safety and tolerability of tipifarnib, and the assessment of ORR, PFS, and DOR in subgroups defined according to genetic subtypes. Eligible subjects received tipifarnib administered at a starting dose of 300 mg, orally with food, twice daily (BID) on Days 1-21 in 28-day cycles (i.e., 3 weeks on/1 week off). In the absence of unmanageable toxicities, subjects may have continued to receive tipifarnib treatment for up to 12 months in the absence of disease progression. Tumour assessments were performed at screening, at the Day 22 visit (±5 days), during Cycles 2, 4, 6, and once every approximately 12 weeks (Cycles 9, 12, 15, etc.) thereafter, until disease progression. Determination of objective tumour response was performed based on the Lugano Classification. Upon disease progression, subjects were followed approximately every 12 weeks for survival until either death or 12 months after accrual of the last study subject, whichever occurred first. All subjects were followed-up for safety during treatment and for approximately 30 additional days after treatment discontinuation.

Trial information Top of page
Trial identification
Sponsor protocol code	KO-TIP-002
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Kura Oncology, Inc
Sponsor organisation address	12730 High Bluff Drive, San Diego, United States, CA 92130
Public contact	Information desk, Kura Oncology, Inc, 001 8585008800, info@kuraoncology.com
Scientific contact	Information desk, Kura Oncology, Inc, 001 8585008800, info@kuraoncology.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	31 Mar 2021
Is this the analysis of the primary completion data?	Yes
Primary completion date	31 Mar 2021
Global end of trial reached?	Yes
Global end of trial date	31 Mar 2021
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To determine the antitumour activity in terms of ORR of tipifarnib in subjects with relapsed or refractory PTCL. Subjects were enrolled into 4 cohorts based on the type of lymphoma: angioimmunoblastic T-cell lymphoma (AITL), PTCL not otherwise specified (PTCL-NOS), PTCL-NOS with CXCL12+ (C-X-C motif chemokine 12+), and Other. For the purposes of the analysis an additional reporting group was defined combining patients from both the PTCL-NOS and PTCL-NOS CXCL12+ groups.
Protection of trial subjects	This trial was designed and monitored in accordance with sponsor procedures, which comply with the ethical principles of Good Clinical Practice (GCP) as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki. The protocol, informed consent form (ICF), and other relevant study documentation were approved by the independent ethics committee (IEC)/institutional review boards (IRBs) before initiation of the study.
Background therapy	All prescription and over-the-counter medications taken by a subject within 28 days before the first study drug administration were recorded in the electronic case report form (eCRF). Supportive care medications considered necessary for the subject’s safety and well-being may have been given at the discretion of the investigator. Any concomitant medications added or discontinued during the study were recorded on the eCRF. Best supportive care (BSC) was provided by the clinical study sites according to local guidelines and standard practices. Furthermore, the following treatments were allowed during the trial: • Intravenous hydration • Correction of electrolyte deficiencies • Haematopoietic growth factors and transfusions of blood or blood products in subjects who were experiencing haematological toxicity in accordance with standard institutional practice • Radiotherapy for pain control against non-target lesions as long as it did not influence bone marrow function • Total tumour resection in responding subjects who had become candidates for curative resection Any additional concomitant therapy that became necessary during the trial and any change to concomitant drugs were recorded in the corresponding section of the eCRF, noting the name, dose, duration, and indication of each drug.
Evidence for comparator	-
Actual start date of recruitment	08 Oct 2015
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Spain: 13
Country: Number of subjects enrolled	Korea, Republic of: 12
Country: Number of subjects enrolled	United States: 40
Worldwide total number of subjects	65
EEA total number of subjects	13
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	26
From 65 to 84 years	37
85 years and over	2

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	The first patient was enrolled on 25 Feb 2016 (13 in Europe; 52 outside Europe) and the date of the last visit was 31 Mar 2021. Overall, 65 patients were enrolled into cohorts with AITL, PTCL-NOS, PTCL-NOS CXCL12+, and Other (ALCL-ALK neg and PTCL-subtype not spec). For the analysis, a combined group of PTCL-NOS and PTCL-NOS CXCL12+ was defined.
Pre-assignment
Screening details	Only consented subjects who met all the eligibility criteria were enrolled in the study. All screening evaluations were to be completed within 4 weeks (28 days) of Cycle 1 Day 1. Screen failure reasons were not included in the database.
Period 1
Period 1 title	Baseline (overall period)
Is this the baseline period?	Yes
Allocation method	Non-randomised - controlled
Blinding used	Not blinded
Blinding implementation details	No blinding was used; this was an open-label study with no placebo or comparators.
Arms
Are arms mutually exclusive	No
Arm title	Cohort AITL
Arm description	Subjects with angioimmunoblastic T-cell lymphoma (AITL).
Arm type	Experimental
Investigational medicinal product name	Tipifarnib
Investigational medicinal product code
Other name
Pharmaceutical forms	Film-coated tablet
Routes of administration	Oral use
Dosage and administration details	Subjects received tipifarnib as monotherapy. Tipifarnib was administered with food at a starting dose of 300 mg administered orally BID on Days 1 – 21 of 28 -day treatment cycles. Subjects who received tipifarnib 300 mg administered orally BID on Days 1 – 7 and Days 15 – 21 during the conduct of earlier versions of this protocol may have remained on that dose regimen at the discretion of the investigator. Alternatively, the subject may have transitioned to receive a dose of 300 mg administered orally BID on Days 1 – 21 of 28-day treatment cycles beginning on Day 1 of their next cycle. The first study dosing (Cycle 1 Day 1) took place in the study clinic. Subjects were provided with diaries with instructions to record the date and time of each dose and were asked to bring the diaries and tablet bottles to each clinic visit for subject compliance and drug accountability review by the site staff.
Arm title	Cohort PTCL-NOS
Arm description	Subjects with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS).
Arm type	Experimental
Investigational medicinal product name	Tipifarnib
Investigational medicinal product code
Other name
Pharmaceutical forms	Film-coated tablet
Routes of administration	Oral use
Dosage and administration details	Subjects received tipifarnib as monotherapy. Tipifarnib was administered with food at a starting dose of 300 mg administered orally BID on Days 1 – 21 of 28 -day treatment cycles. Subjects who received tipifarnib 300 mg administered orally BID on Days 1 – 7 and Days 15 – 21 during the conduct of earlier versions of this protocol may have remained on that dose regimen at the discretion of the investigator. Alternatively, the subject may have transitioned to receive a dose of 300 mg administered orally BID on Days 1 – 21 of 28-day treatment cycles beginning on Day 1 of their next cycle. The first study dosing (Cycle 1 Day 1) took place in the study clinic. Subjects were provided with diaries with instructions to record the date and time of each dose and were asked to bring the diaries and tablet bottles to each clinic visit for subject compliance and drug accountability review by the site staff.
Arm title	Cohort PTCL-NOS, CXCL12+
Arm description	Subjects with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) whose tumours expressed high levels of C-X-C motif chemokine 12 (CXCL12).
Arm type	Experimental
Investigational medicinal product name	Tipifarnib
Investigational medicinal product code
Other name
Pharmaceutical forms	Film-coated tablet
Routes of administration	Oral use
Dosage and administration details	Subjects received tipifarnib as monotherapy. Tipifarnib was administered with food at a starting dose of 300 mg administered orally BID on Days 1 – 21 of 28 -day treatment cycles. Subjects who received tipifarnib 300 mg administered orally BID on Days 1 – 7 and Days 15 – 21 during the conduct of earlier versions of this protocol may have remained on that dose regimen at the discretion of the investigator. Alternatively, the subject may have transitioned to receive a dose of 300 mg administered orally BID on Days 1 – 21 of 28-day treatment cycles beginning on Day 1 of their next cycle. The first study dosing (Cycle 1 Day 1) took place in the study clinic. Subjects were provided with diaries with instructions to record the date and time of each dose and were asked to bring the diaries and tablet bottles to each clinic visit for subject compliance and drug accountability review by the site staff.
Arm title	Cohort PTCL-NOS, Overall
Arm description	All subjects with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) from the PTCL-NOS and PTCL-NOS CXCL12+ cohorts combined. For the purposes of the analysis an additional reporting group was defined combining patients from both the PTCL-NOS and PTCL-NOS CXCL12+ groups.
Arm type	Experimental
Investigational medicinal product name	Tipifarnib
Investigational medicinal product code
Other name
Pharmaceutical forms	Film-coated tablet
Routes of administration	Oral use
Dosage and administration details	Subjects received tipifarnib as monotherapy. Tipifarnib was administered with food at a starting dose of 300 mg administered orally BID on Days 1 – 21 of 28 -day treatment cycles. Subjects who received tipifarnib 300 mg administered orally BID on Days 1 – 7 and Days 15 – 21 during the conduct of earlier versions of this protocol may have remained on that dose regimen at the discretion of the investigator. Alternatively, the subject may have transitioned to receive a dose of 300 mg administered orally BID on Days 1 – 21 of 28-day treatment cycles beginning on Day 1 of their next cycle. The first study dosing (Cycle 1 Day 1) took place in the study clinic. Subjects were provided with diaries with instructions to record the date and time of each dose and were asked to bring the diaries and tablet bottles to each clinic visit for subject compliance and drug accountability review by the site staff.
Arm title	Cohort Other
Arm description	Subjects with Other, including anaplastic large cell lymphoma-anaplastic lymphoma kinase (ALCL-ALK) negative and PTCL-subtype not specified per protocol.
Arm type	Experimental
Investigational medicinal product name	Tipifarnib
Investigational medicinal product code
Other name
Pharmaceutical forms	Film-coated tablet
Routes of administration	Oral use
Dosage and administration details	Subjects received tipifarnib as monotherapy. Tipifarnib was administered with food at a starting dose of 300 mg administered orally BID on Days 1 – 21 of 28 -day treatment cycles. Subjects who received tipifarnib 300 mg administered orally BID on Days 1 – 7 and Days 15 – 21 during the conduct of earlier versions of this protocol may have remained on that dose regimen at the discretion of the investigator. Alternatively, the subject may have transitioned to receive a dose of 300 mg administered orally BID on Days 1 – 21 of 28-day treatment cycles beginning on Day 1 of their next cycle. The first study dosing (Cycle 1 Day 1) took place in the study clinic. Subjects were provided with diaries with instructions to record the date and time of each dose and were asked to bring the diaries and tablet bottles to each clinic visit for subject compliance and drug accountability review by the site staff.
Number of subjects in period 1 Cohort AITL Cohort PTCL-NOS Cohort PTCL-NOS, CXCL12+ Cohort PTCL-NOS, Overall Cohort Other Started 38 14 11 25 2 Completed 2 0 0 0 0 Not completed 36 14 11 25 2      Consent withdrawn by subject 1 1 1 2 -      Disease progression 22 12 5 17 2      PI decision 2 - 1 1 -      Adverse event, non-fatal 9 - 3 3 -      Not specified 1 - 1 1 -      Termination for symptomatic deterioration 1 1 - 1 -

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Cohort AITL
Reporting group description	Subjects with angioimmunoblastic T-cell lymphoma (AITL).
Reporting group title	Cohort PTCL-NOS
Reporting group description	Subjects with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS).
Reporting group title	Cohort PTCL-NOS, CXCL12+
Reporting group description	Subjects with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) whose tumours expressed high levels of C-X-C motif chemokine 12 (CXCL12).
Reporting group title	Cohort PTCL-NOS, Overall
Reporting group description	All subjects with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) from the PTCL-NOS and PTCL-NOS CXCL12+ cohorts combined. For the purposes of the analysis an additional reporting group was defined combining patients from both the PTCL-NOS and PTCL-NOS CXCL12+ groups.
Reporting group title	Cohort Other
Reporting group description	Subjects with Other, including anaplastic large cell lymphoma-anaplastic lymphoma kinase (ALCL-ALK) negative and PTCL-subtype not specified per protocol.
Reporting group values Cohort AITL Cohort PTCL-NOS Cohort PTCL-NOS, CXCL12+ Cohort PTCL-NOS, Overall Cohort Other Total Number of subjects 38 14 11 25 2 Age categorical Units: Subjects Age continuous Units: years     arithmetic mean (standard deviation) 65.50 ( 10.7 ) 65.73 ( 13.7 ) 65.74 ( 12.6 ) 65.73 ( 12.9 ) 56.68 ( 12.0 ) - Gender categorical Units: Subjects     Female 16 2 5 7 1 24     Male 22 12 6 18 1 41 ECOG performance score Units: Subjects     Performance score 0 18 3 5 8 0 26     Performance score 1 13 10 6 16 2 31     Performance score 2 7 1 0 1 0 8     Other 0 0 0 0 0 0

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Cohort AITL
Reporting group description	Subjects with angioimmunoblastic T-cell lymphoma (AITL).
Reporting group title	Cohort PTCL-NOS
Reporting group description	Subjects with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS).
Reporting group title	Cohort PTCL-NOS, CXCL12+
Reporting group description	Subjects with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) whose tumours expressed high levels of C-X-C motif chemokine 12 (CXCL12).
Reporting group title	Cohort PTCL-NOS, Overall
Reporting group description	All subjects with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) from the PTCL-NOS and PTCL-NOS CXCL12+ cohorts combined. For the purposes of the analysis an additional reporting group was defined combining patients from both the PTCL-NOS and PTCL-NOS CXCL12+ groups.
Reporting group title	Cohort Other
Reporting group description	Subjects with Other, including anaplastic large cell lymphoma-anaplastic lymphoma kinase (ALCL-ALK) negative and PTCL-subtype not specified per protocol.

End points Top of page

Primary: Antitumor activity by overall objective response rate Top of page
End point title	Antitumor activity by overall objective response rate [1]
End point description	The objective response rate (ORR) of tipifarnib was based on response assessments according to the Lugano Classification. Either complete responses (CRs) or partial responses (PRs) contributed to an objective response. 2-sided 95% CIs were based on either Wilson approximation (N > 4) or Clopper-Pearson method (N ≤ 4). P-value was calculated testing an overall response of 10% using a 2-sided binomial test. P- values by cohort: AITL = 0.000 PTCL-NOS = 1.000 PTCL, CXCL12+ = 0.026 PTCL-NOS, Overall = 0.077 Other = 1.000
End point type	Primary
End point timeframe	From baseline to end of follow-up.
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There were no between group comparisons for the primary endpoint. Each group was compared against a target rate of 10%. The statistical analysis is therefore described under 'Description of the endpoint'.
End point values Cohort AITL Cohort PTCL-NOS Cohort PTCL-NOS, CXCL12+ Cohort PTCL-NOS, Overall Cohort Other Number of subjects analysed 32 14 10 24 2 Units: percent     arithmetic mean (confidence interval 95%) 56.3 (39.3 to 71.8) 7.1 (0.2 to 33.9) 40.0 (12.2 to 73.8) 20.8 (9.2 to 40.5) 0.0 (0.0 to 84.2)
No statistical analyses for this end point

Primary: Antitumor activity by overall objective response rate Top of page

Secondary: Progression-free survival Top of page
End point title	Progression-free survival
End point description	Progression-free survival (PFS) was defined as the time (in months) from first dose (Cycle 1 Day 1) to either first observation of progressive disease (PD) or occurrence of death due to any cause within 126 days (approximately 2 time-intervals for tumour assessments) of either first administration of tipifarnib or the last tumour assessment. Observation of PD could have been by either documented radiographic progression (i.e., scan results) or documentation of symptomatic or clinical progression agreed upon and documented by investigators. In subjects without a progression date or with a death date more than 126 days after the first administration of study drugs or the last tumour assessment, the PFS time should have been censored on the date of last tumour assessment or date of first administration of study tipifarnib. 95% CI was calculated using Hall-Wellner Method.
End point type	Secondary
End point timeframe	From baseline to end of follow-up.
End point values Cohort AITL Cohort PTCL-NOS Cohort PTCL-NOS, CXCL12+ Cohort PTCL-NOS, Overall Cohort Other Number of subjects analysed 32 14 10 24 2 Units: Months     median (confidence interval 95%) 3.6 (1.9 to 8.3) 2.1 (1.4 to 4.0) 5.3 (1.8 to 11.1) 3.5 (1.8 to 5.3) 1.4 (1.1 to 1.6)
No statistical analyses for this end point

Secondary: Progression-free survival Top of page

Secondary: Duration of response Top of page
End point title	Duration of response [2]
End point description	The duration of the objective response (DOR) was defined as the time (in months) from the start date of the objective response to the first date of either documented PD or death. All efforts were made to objectively define the endpoint by collecting the necessary data and reducing the likelihood of missing data. No data imputations were conducted for missing data. In the event of a maintained response, the DOR was censored at the last evaluable non-PD assessment. Data are presented for cohorts for which median and 95% CI were calculable (Kaplan-Meier analysis). 95% CI was calculated using Hall-Wellner Method. Where not calculable (NC), median (95% CI) listed below; N = number of responders: PTCL-NOS (N = 1): 1.0 (NC, NC) PTCL-NOS, CXCL12+ (N = 4): 2.8 (2.0, NC) PTCL-NOS, Overall (N = 5): 2.0 (1.0, NC) Other (N = 0): NC (NC, NC)
End point type	Secondary
End point timeframe	From baseline to end of follow-up.
Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: For several cohorts, 95% CI were not estimable for median duration of response, therefore statistical analysis could only be described under 'Description of the endpoint'.
End point values Cohort AITL Number of subjects analysed 18 Units: months     median (confidence interval 95%) 7.8 (2.0 to 16.3)
No statistical analyses for this end point

Secondary: Duration of response Top of page

Secondary: Antitumor activity - best overall response Top of page
End point title	Antitumor activity - best overall response
End point description	Best overall response according to the Lugano Classification was summarised using descriptive statistics.
End point type	Secondary
End point timeframe	From baseline to end of follow-up.
End point values Cohort AITL Cohort PTCL-NOS Cohort PTCL-NOS, CXCL12+ Cohort PTCL-NOS, Overall Cohort Other Number of subjects analysed 32 14 10 24 2 Units: Subjects     Complete response 9 0 1 1 0     Partial response 9 1 3 4 0     Stable disease 3 4 5 9 0     Progressive disease 11 8 1 9 2     Not evaluable 0 1 0 1 0
No statistical analyses for this end point

Secondary: Antitumor activity - best overall response Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	From the date of first signature of informed consent through the post-treatment follow-up period, defined as 30 days from final administration of study drug or immediately before initiation of any other anticancer therapy, whichever came first.
Adverse event reporting additional description	The 5% cut-off for reporting of non-serious AEs (non-SAEs) was based on the percentages within individual cohorts.
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	19.0
Reporting groups
Reporting group title	Cohort AITL
Reporting group description	Subjects with angioimmunoblastic T-cell lymphoma (AITL).
Reporting group title	Cohort PTCL-NOS
Reporting group description	Subjects with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS).
Reporting group title	Cohort PTCL-NOS, CXCL12+
Reporting group description	Subjects with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) whose tumours expressed high levels of C-X-C motif chemokine 12 (CXCL12).
Reporting group title	Cohort PTCL-NOS, Overall
Reporting group description	All subjects with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) from the other cohorts combined.
Reporting group title	Cohort Other
Reporting group description	Subjects with Other, including ALCL-ALK Negative and PTCL-subtype not specified per protocol.
Serious adverse events Cohort AITL Cohort PTCL-NOS Cohort PTCL-NOS, CXCL12+ Cohort PTCL-NOS, Overall Cohort Other Total subjects affected by serious adverse events      subjects affected / exposed 21 / 38 (55.26%) 8 / 14 (57.14%) 8 / 11 (72.73%) 16 / 25 (64.00%) 1 / 2 (50.00%)      number of deaths (all causes) 13 8 4 12 1      number of deaths resulting from adverse events 4 1 1 2 0 Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Myelodysplastic syndrome      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Squamous cell carcinoma of lung      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Tumour pain      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 General disorders and administration site conditions Death      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 Pyrexia      subjects affected / exposed 2 / 38 (5.26%) 3 / 14 (21.43%) 1 / 11 (9.09%) 4 / 25 (16.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 2 / 3 0 / 3 0 / 1 0 / 4 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Malaise      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Respiratory, thoracic and mediastinal disorders Dyspnoea      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Hypoxia      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Respiratory failure      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0 Psychiatric disorders Delirium      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Confusional state      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Investigations Platelet count decreased      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Injury, poisoning and procedural complications Fall      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 1 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Femoral neck fracture      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Overdose      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Cardiac disorders Atrial fibrillation      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Atrioventricular block second degree      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Cardiac failure      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Cardiopulmonary failure      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 Myocardial infarction      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Nervous system disorders Encephalopathy      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Syncope      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Blood and lymphatic system disorders Febrile neutropenia      subjects affected / exposed 3 / 38 (7.89%) 4 / 14 (28.57%) 0 / 11 (0.00%) 4 / 25 (16.00%) 1 / 2 (50.00%)      occurrences causally related to treatment / all 2 / 3 4 / 4 0 / 0 4 / 4 1 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Haemolytic anaemia      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Neutropenia      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0 1 / 1 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Pancytopenia      subjects affected / exposed 3 / 38 (7.89%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 3 / 3 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Anaemia      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Cytopenia      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Histiocytosis haematophagic      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Gastrointestinal disorders Colitis      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Diarrhoea      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Vomiting      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 1 / 1 0 / 0 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Hepatobiliary disorders Cholelithiasis      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Skin and subcutaneous tissue disorders Stevens-Johnson syndrome      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Urticaria      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 1 / 2 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Toxic skin eruption      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Renal and urinary disorders Acute kidney injury      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 1 / 1 0 / 0 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Musculoskeletal and connective tissue disorders Muscular weakness      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Joint effusion      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Infections and infestations Cellulitis      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 1 / 1 0 / 0 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Bacteraemia      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Kidney infection      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Lung infection      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 Pneumocystis jirovecii pneumonia      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Pneumonia      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Sepsis      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 1 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 1 0 / 0 Urinary tract infection      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 2 0 / 0 0 / 1 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Metabolism and nutrition disorders Dehydration      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 2 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 Hypercalcaemia      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Hypokalaemia      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Failure to thrive      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events Cohort AITL Cohort PTCL-NOS Cohort PTCL-NOS, CXCL12+ Cohort PTCL-NOS, Overall Cohort Other Total subjects affected by non serious adverse events      subjects affected / exposed 38 / 38 (100.00%) 14 / 14 (100.00%) 11 / 11 (100.00%) 25 / 25 (100.00%) 2 / 2 (100.00%) Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 2 2 0 Vascular disorders Deep vein thrombosis      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Haematoma      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 1 0 1 1 0 Hypotension      subjects affected / exposed 8 / 38 (21.05%) 2 / 14 (14.29%) 1 / 11 (9.09%) 3 / 25 (12.00%) 0 / 2 (0.00%)      occurrences all number 8 2 2 4 0 Peripheral coldness      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 General disorders and administration site conditions Asthenia      subjects affected / exposed 3 / 38 (7.89%) 3 / 14 (21.43%) 3 / 11 (27.27%) 6 / 25 (24.00%) 0 / 2 (0.00%)      occurrences all number 3 3 4 7 0 Chest pain      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 2 1 0 1 0 Chills      subjects affected / exposed 4 / 38 (10.53%) 1 / 14 (7.14%) 2 / 11 (18.18%) 3 / 25 (12.00%) 1 / 2 (50.00%)      occurrences all number 5 2 3 5 1 Fatigue      subjects affected / exposed 19 / 38 (50.00%) 7 / 14 (50.00%) 2 / 11 (18.18%) 9 / 25 (36.00%) 0 / 2 (0.00%)      occurrences all number 23 7 2 9 0 Gait disturbance      subjects affected / exposed 2 / 38 (5.26%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 2 1 0 1 0 Decreased activity      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Influenza like illness      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 1 2 1 3 0 Malaise      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 2 / 11 (18.18%) 3 / 25 (12.00%) 1 / 2 (50.00%)      occurrences all number 1 1 3 4 1 Oedema peripheral      subjects affected / exposed 3 / 38 (7.89%) 3 / 14 (21.43%) 4 / 11 (36.36%) 7 / 25 (28.00%) 0 / 2 (0.00%)      occurrences all number 4 3 5 8 0 Pain      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 1 / 2 (50.00%)      occurrences all number 2 0 1 1 1 Medical device pain      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Non-cardiac chest pain      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 0 1 1 2 0 Pyrexia      subjects affected / exposed 13 / 38 (34.21%) 2 / 14 (14.29%) 3 / 11 (27.27%) 5 / 25 (20.00%) 1 / 2 (50.00%)      occurrences all number 17 2 7 9 1 Reproductive system and breast disorders Gynaecomastia      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Respiratory, thoracic and mediastinal disorders Cough      subjects affected / exposed 8 / 38 (21.05%) 3 / 14 (21.43%) 2 / 11 (18.18%) 5 / 25 (20.00%) 0 / 2 (0.00%)      occurrences all number 9 3 2 5 0 Dysphonia      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 2 0 0 0 0 Dyspnoea      subjects affected / exposed 4 / 38 (10.53%) 6 / 14 (42.86%) 0 / 11 (0.00%) 6 / 25 (24.00%) 1 / 2 (50.00%)      occurrences all number 5 6 0 6 1 Dyspnoea exertional      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Epistaxis      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 1 0 1 1 0 Hiccups      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Nasal congestion      subjects affected / exposed 3 / 38 (7.89%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 3 1 1 2 0 Oropharyngeal pain      subjects affected / exposed 3 / 38 (7.89%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 1 / 2 (50.00%)      occurrences all number 3 1 1 2 1 Pleural effusion      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 2 0 0 0 0 Productive cough      subjects affected / exposed 2 / 38 (5.26%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 2 2 0 2 0 Pulmonary mass      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Rhinorrhoea      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 2 0 0 0 0 Psychiatric disorders Abnormal dreams      subjects affected / exposed 0 / 38 (0.00%) 2 / 14 (14.29%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 2 0 2 0 Agitation      subjects affected / exposed 0 / 38 (0.00%) 2 / 14 (14.29%) 0 / 11 (0.00%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 0 2 0 2 0 Anxiety      subjects affected / exposed 3 / 38 (7.89%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 4 0 0 0 0 Confusional state      subjects affected / exposed 1 / 38 (2.63%) 2 / 14 (14.29%) 1 / 11 (9.09%) 3 / 25 (12.00%) 0 / 2 (0.00%)      occurrences all number 1 2 1 3 0 Disorientation      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Insomnia      subjects affected / exposed 5 / 38 (13.16%) 3 / 14 (21.43%) 1 / 11 (9.09%) 4 / 25 (16.00%) 1 / 2 (50.00%)      occurrences all number 5 3 1 4 1 Investigations Alanine aminotransferase increased      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 1 1 1 2 0 Aspartate aminotransferase increased      subjects affected / exposed 2 / 38 (5.26%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 2 2 1 3 0 Blood alkaline phosphatase increased      subjects affected / exposed 1 / 38 (2.63%) 2 / 14 (14.29%) 0 / 11 (0.00%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 1 2 0 2 0 Blood bilirubin increased      subjects affected / exposed 0 / 38 (0.00%) 3 / 14 (21.43%) 0 / 11 (0.00%) 3 / 25 (12.00%) 0 / 2 (0.00%)      occurrences all number 0 6 0 6 0 Blood creatinine increased      subjects affected / exposed 5 / 38 (13.16%) 5 / 14 (35.71%) 1 / 11 (9.09%) 6 / 25 (24.00%) 0 / 2 (0.00%)      occurrences all number 5 6 1 7 0 Blood lactate dehydrogenase increased      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Blood urea increased      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Blood uric acid increased      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 CD4 lymphocytes decreased      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 2 2 0 Epstein-Barr virus test positive      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Gamma-glutamyltransferase increased      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 4 0 0 0 0 Human rhinovirus test positive      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 International normalised ratio increased      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 1 1 2 3 0 Lymphocyte count decreased      subjects affected / exposed 4 / 38 (10.53%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 8 2 0 2 0 Lymphocyte count increased      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 2 2 0 Monocyte count decreased      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Neutrophil count decreased      subjects affected / exposed 11 / 38 (28.95%) 8 / 14 (57.14%) 1 / 11 (9.09%) 9 / 25 (36.00%) 0 / 2 (0.00%)      occurrences all number 37 25 3 28 0 Platelet count decreased      subjects affected / exposed 15 / 38 (39.47%) 10 / 14 (71.43%) 4 / 11 (36.36%) 14 / 25 (56.00%) 1 / 2 (50.00%)      occurrences all number 35 14 8 22 1 Urine output increased      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 2 0 2 0 Weight decreased      subjects affected / exposed 4 / 38 (10.53%) 6 / 14 (42.86%) 2 / 11 (18.18%) 8 / 25 (32.00%) 0 / 2 (0.00%)      occurrences all number 4 6 3 9 0 White blood cell count decreased      subjects affected / exposed 4 / 38 (10.53%) 3 / 14 (21.43%) 2 / 11 (18.18%) 5 / 25 (20.00%) 0 / 2 (0.00%)      occurrences all number 11 8 2 10 0 Injury, poisoning and procedural complications Contusion      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 2 / 11 (18.18%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 3 0 2 2 0 Eye injury      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Fall      subjects affected / exposed 3 / 38 (7.89%) 2 / 14 (14.29%) 0 / 11 (0.00%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 3 2 0 2 0 Humerus fracture      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Joint injury      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Periorbital haemorrhage      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Radiation pneumonitis      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Thermal burn      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Cardiac disorders Atrial fibrillation      subjects affected / exposed 3 / 38 (7.89%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 3 0 0 0 0 Sinus tachycardia      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 1 0 1 1 0 Tachycardia      subjects affected / exposed 2 / 38 (5.26%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 1 / 2 (50.00%)      occurrences all number 3 1 0 1 1 Palpitations      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Ventricular arrhythmia      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Nervous system disorders Dizziness      subjects affected / exposed 8 / 38 (21.05%) 2 / 14 (14.29%) 0 / 11 (0.00%) 2 / 25 (8.00%) 1 / 2 (50.00%)      occurrences all number 9 2 0 2 1 Dysarthria      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Dysgeusia      subjects affected / exposed 2 / 38 (5.26%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 2 1 1 2 0 Haemorrhage intracranial      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Headache      subjects affected / exposed 5 / 38 (13.16%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 2 / 2 (100.00%)      occurrences all number 5 0 0 0 2 Paraesthesia      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 2 2 0 Peripheral sensory neuropathy      subjects affected / exposed 4 / 38 (10.53%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 6 2 0 2 0 Sciatica      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Sinus headache      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 1 1 0 1 0 Somnolence      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Tremor      subjects affected / exposed 0 / 38 (0.00%) 2 / 14 (14.29%) 0 / 11 (0.00%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 0 2 0 2 0 Blood and lymphatic system disorders Anaemia      subjects affected / exposed 16 / 38 (42.11%) 10 / 14 (71.43%) 6 / 11 (54.55%) 16 / 25 (64.00%) 1 / 2 (50.00%)      occurrences all number 32 17 9 26 1 Febrile neutropenia      subjects affected / exposed 2 / 38 (5.26%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 2 1 0 1 0 Leukopenia      subjects affected / exposed 1 / 38 (2.63%) 4 / 14 (28.57%) 0 / 11 (0.00%) 4 / 25 (16.00%) 1 / 2 (50.00%)      occurrences all number 1 5 0 5 1 Lymphopenia      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 1 1 2 3 0 Neutropenia      subjects affected / exposed 6 / 38 (15.79%) 4 / 14 (28.57%) 3 / 11 (27.27%) 7 / 25 (28.00%) 0 / 2 (0.00%)      occurrences all number 11 5 9 14 0 Thrombocytopenia      subjects affected / exposed 3 / 38 (7.89%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 8 0 1 1 0 Splenomegaly      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Ear and labyrinth disorders Ear pain      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 1 / 2 (50.00%)      occurrences all number 0 0 1 1 1 Eye disorders Vision blurred      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 2 0 0 0 0 Macular degeneration      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Vitreous floaters      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Gastrointestinal disorders Abdominal pain      subjects affected / exposed 5 / 38 (13.16%) 2 / 14 (14.29%) 2 / 11 (18.18%) 4 / 25 (16.00%) 0 / 2 (0.00%)      occurrences all number 5 3 3 6 0 Abdominal pain lower      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Abdominal pain upper      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Abdominal discomfort      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Abdominal distension      subjects affected / exposed 0 / 38 (0.00%) 2 / 14 (14.29%) 1 / 11 (9.09%) 3 / 25 (12.00%) 1 / 2 (50.00%)      occurrences all number 0 2 2 4 1 Constipation      subjects affected / exposed 5 / 38 (13.16%) 5 / 14 (35.71%) 1 / 11 (9.09%) 6 / 25 (24.00%) 0 / 2 (0.00%)      occurrences all number 5 7 1 8 0 Diarrhoea      subjects affected / exposed 14 / 38 (36.84%) 8 / 14 (57.14%) 2 / 11 (18.18%) 10 / 25 (40.00%) 1 / 2 (50.00%)      occurrences all number 28 9 5 14 1 Dyspepsia      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 2 / 11 (18.18%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 2 0 2 2 0 Dysphagia      subjects affected / exposed 5 / 38 (13.16%) 0 / 14 (0.00%) 2 / 11 (18.18%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 5 0 2 2 0 Dry mouth      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 1 / 2 (50.00%)      occurrences all number 0 0 0 0 1 Gastritis      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 2 0 0 0 0 Gastrointestinal wall thickening      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Gastrooesophageal reflux disease      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Gingival pain      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Nausea      subjects affected / exposed 12 / 38 (31.58%) 9 / 14 (64.29%) 4 / 11 (36.36%) 13 / 25 (52.00%) 1 / 2 (50.00%)      occurrences all number 17 9 5 14 1 Stomatitis      subjects affected / exposed 3 / 38 (7.89%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 3 0 1 1 0 Toothache      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 1 1 1 2 0 Vomiting      subjects affected / exposed 6 / 38 (15.79%) 5 / 14 (35.71%) 3 / 11 (27.27%) 8 / 25 (32.00%) 0 / 2 (0.00%)      occurrences all number 8 5 4 9 0 Hepatobiliary disorders Cholecystitis      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Skin and subcutaneous tissue disorders Dermatitis acneiform      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Erythema multiforme      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 1 / 2 (50.00%)      occurrences all number 2 0 0 0 1 Hyperhidrosis      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 2 0 2 0 Ingrowing nail      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 2 0 0 0 0 Night sweats      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Onychomadesis      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Pruritus      subjects affected / exposed 10 / 38 (26.32%) 0 / 14 (0.00%) 2 / 11 (18.18%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 11 0 4 4 0 Rash      subjects affected / exposed 9 / 38 (23.68%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 11 0 0 0 0 Rash macular      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Rash maculo-papular      subjects affected / exposed 5 / 38 (13.16%) 0 / 14 (0.00%) 2 / 11 (18.18%) 2 / 25 (8.00%) 1 / 2 (50.00%)      occurrences all number 7 0 6 6 1 Skin lesion      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 0 1 4 5 0 Urticaria      subjects affected / exposed 5 / 38 (13.16%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 5 0 0 0 0 Renal and urinary disorders Acute kidney injury      subjects affected / exposed 2 / 38 (5.26%) 3 / 14 (21.43%) 0 / 11 (0.00%) 3 / 25 (12.00%) 0 / 2 (0.00%)      occurrences all number 2 3 0 3 0 Haematuria      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Nocturia      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Renal colic      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Urinary retention      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 1 1 0 1 0 Urine abnormality      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Musculoskeletal and connective tissue disorders Arthralgia      subjects affected / exposed 3 / 38 (7.89%) 4 / 14 (28.57%) 2 / 11 (18.18%) 6 / 25 (24.00%) 0 / 2 (0.00%)      occurrences all number 4 4 3 7 0 Back pain      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 2 / 11 (18.18%) 3 / 25 (12.00%) 1 / 2 (50.00%)      occurrences all number 1 1 2 3 1 Bone pain      subjects affected / exposed 2 / 38 (5.26%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 2 1 3 4 0 Flank pain      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 2 0 0 0 0 Groin pain      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 1 / 2 (50.00%)      occurrences all number 0 1 0 1 1 Muscle spasms      subjects affected / exposed 1 / 38 (2.63%) 2 / 14 (14.29%) 0 / 11 (0.00%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 1 3 0 3 0 Muscular weakness      subjects affected / exposed 7 / 38 (18.42%) 0 / 14 (0.00%) 3 / 11 (27.27%) 3 / 25 (12.00%) 0 / 2 (0.00%)      occurrences all number 10 0 3 3 0 Myalgia      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 1 1 0 1 0 Neck pain      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 1 / 2 (50.00%)      occurrences all number 0 0 0 0 1 Pain in extremity      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 1 / 2 (50.00%)      occurrences all number 2 0 1 1 1 Scoliosis      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Synovitis      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Infections and infestations Bacterial infection      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Clostridium difficile infection      subjects affected / exposed 1 / 38 (2.63%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 1 0 2 2 0 Diverticulitis      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Dermatitis infected      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Epstein-Barr virus infection      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Herpes zoster      subjects affected / exposed 2 / 38 (5.26%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 1 / 2 (50.00%)      occurrences all number 2 0 0 0 1 Oral candidiasis      subjects affected / exposed 4 / 38 (10.53%) 0 / 14 (0.00%) 2 / 11 (18.18%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 4 0 2 2 0 Pharyngitis      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 2 / 11 (18.18%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 0 0 2 2 0 Pneumonia      subjects affected / exposed 4 / 38 (10.53%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 4 1 1 2 0 Rash pustular      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 2 0 2 0 Sepsis      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 1 1 0 1 0 Sinusitis      subjects affected / exposed 2 / 38 (5.26%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 2 1 0 1 0 Streptoccocal urinary tract infection      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0 Upper respiratory tract infection      subjects affected / exposed 5 / 38 (13.16%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 0 / 2 (0.00%)      occurrences all number 5 0 0 0 0 Urinary tract infection      subjects affected / exposed 3 / 38 (7.89%) 1 / 14 (7.14%) 1 / 11 (9.09%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 3 1 1 2 0 Skin infection      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 0 / 11 (0.00%) 0 / 25 (0.00%) 1 / 2 (50.00%)      occurrences all number 0 0 0 0 1 Metabolism and nutrition disorders Decreased appetite      subjects affected / exposed 13 / 38 (34.21%) 7 / 14 (50.00%) 2 / 11 (18.18%) 9 / 25 (36.00%) 1 / 2 (50.00%)      occurrences all number 16 8 3 11 1 Dehydration      subjects affected / exposed 5 / 38 (13.16%) 4 / 14 (28.57%) 0 / 11 (0.00%) 4 / 25 (16.00%) 0 / 2 (0.00%)      occurrences all number 6 5 0 5 0 Hypercalcaemia      subjects affected / exposed 3 / 38 (7.89%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 3 4 0 4 0 Hyperglycaemia      subjects affected / exposed 1 / 38 (2.63%) 2 / 14 (14.29%) 0 / 11 (0.00%) 2 / 25 (8.00%) 1 / 2 (50.00%)      occurrences all number 1 2 0 2 1 Hyperkalaemia      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Hyperuricaemia      subjects affected / exposed 2 / 38 (5.26%) 2 / 14 (14.29%) 0 / 11 (0.00%) 2 / 25 (8.00%) 0 / 2 (0.00%)      occurrences all number 2 2 0 2 0 Hypoalbuminaemia      subjects affected / exposed 2 / 38 (5.26%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 2 2 0 2 0 Hypocalcaemia      subjects affected / exposed 2 / 38 (5.26%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 2 3 0 3 0 Hypokalaemia      subjects affected / exposed 9 / 38 (23.68%) 5 / 14 (35.71%) 1 / 11 (9.09%) 6 / 25 (24.00%) 0 / 2 (0.00%)      occurrences all number 15 7 1 8 0 Hypomagnesaemia      subjects affected / exposed 5 / 38 (13.16%) 5 / 14 (35.71%) 0 / 11 (0.00%) 5 / 25 (20.00%) 0 / 2 (0.00%)      occurrences all number 7 6 0 6 0 Hyponatraemia      subjects affected / exposed 2 / 38 (5.26%) 7 / 14 (50.00%) 1 / 11 (9.09%) 8 / 25 (32.00%) 1 / 2 (50.00%)      occurrences all number 3 10 1 11 1 Hypophosphataemia      subjects affected / exposed 1 / 38 (2.63%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 1 1 0 1 0 Hypovolaemia      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Lactic acidosis      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Metabolic acidosis      subjects affected / exposed 0 / 38 (0.00%) 1 / 14 (7.14%) 0 / 11 (0.00%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 1 0 1 0 Vitamin B1 deficiency      subjects affected / exposed 0 / 38 (0.00%) 0 / 14 (0.00%) 1 / 11 (9.09%) 1 / 25 (4.00%) 0 / 2 (0.00%)      occurrences all number 0 0 1 1 0