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Clinical Trial Results:
A Phase 1 Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients with Relapsed or Refractory Malignancies

Summary
EudraCT number	2017-000439-14
Trial protocol	DE NL FR
Global end of trial date	19 Apr 2023

Results information
Results version number	v1(current)
This version publication date	28 Oct 2023
First version publication date	28 Oct 2023
Other versions

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

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Trial information

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Sponsor protocol code

M13-833

ISRCTN number

US NCT number

NCT03236857

WHO universal trial number (UTN)

Sponsor organisation name

AbbVie

Sponsor organisation address

1 North Waukegan Road, North Chicago, IL, United States, 60064

Public contact

Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com

Scientific contact

Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-002018-PIP02-16

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?

Yes

Analysis stage

Final

Date of interim/final analysis

19 Apr 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

19 Apr 2023

Was the trial ended prematurely?

Main objective of the trial

This was an open-label, global, Phase 1, dose determination/cohort expansion study in pediatric and young adult subjects with relapsed or refractory malignancies. In Part 1, Dose Determination subjects with any relapsed or refractory tumor without available curative treatment options were eligible to enroll. In Part 1, Dose Escalation/De-escalation solid tumor subjects without bone marrow involvement were eligible to enroll. During Part 2 (Cohort Expansion), subjects were enrolled into one of five tumor cohorts. Four of the cohorts enrolled subjects with the following malignancies: ALL, AML, NHL, or Neuroblastoma (NBL). A fifth exploratory cohort (referred to as Other Tumors) enrolled subjects with any other tumor that expressed BCL-2 or subjects with TCF3-HLF ALL confirmed during frontline induction therapy. Subjects who had primary brain tumors and disease that was metastatic to the brain were excluded. Subjects with solid tumors enrolled in the fifth cohort were analyzed separately.

Protection of trial subjects

Prior to the initiation of any screening or study-specific procedures, the investigator or her/his representative explained the nature of the study to the participant, parent or guardian and answered all questions regarding this study. Each informed consent was reviewed, signed and dated by the participant, parent or guardian, the person who administered the informed consent, and any other signatories according to local requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

08 Nov 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 18

Country: Number of subjects enrolled

Canada: 16

Country: Number of subjects enrolled

France: 13

Country: Number of subjects enrolled

Germany: 8

Country: Number of subjects enrolled

Netherlands: 1

Country: Number of subjects enrolled

Switzerland: 4

Country: Number of subjects enrolled

United Kingdom: 11

Country: Number of subjects enrolled

United States: 69

Worldwide total number of subjects

140

EEA total number of subjects

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)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Subjects underwent screening procedures within 21 days prior to initial study drug administration.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Acute Lymphoblastic Leukemia (ALL)

Arm description

Participants with acute lymphoblastic leukemia (ALL)

Arm type

Experimental

Investigational medicinal product name

Venetoclax (n=31 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Dispersible tablet, Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Venetoclax was administered orally QD, continuously, in subjects with hematologic malignancies. Subjects who were < 2 years of age were dosed based on age and those who were 2 years and older were dosed based on weight. Subjects with liquid tumors (ALL, AML, NHL) were ramped up over 3 days as follows to achieve 800 mg adult-equivalent target dose: Newborn to < 1 month (2.5 mg Day 1, 5 mg Day 2, and 10 mg Day 3+) 1 month to < 3 months (5 mg Day 1, 10 mg Day 2, and 25 mg Day 3+) 3 months to < 6 months (10 mg Day 1, 25 mg Day 2, and 50 mg Day 3+) 6 months to < 1 year (25 mg Day 1, 50 mg Day 2, and 100 mg Day 3+) 1 year to < 2 years (40 mg Day 1, 80 mg Day 2, and 150 mg Day 3+) 10 kg to < 20 kg (50 mg Day 1, 120 mg Day 2, and 250 mg Day 3+) 20 kg to < 30 kg (80 mg Day 1, 170 mg Day 2, and 350 mg Day 3+) 30 kg to < 45 kg (120 mg Day 1, 250 mg Day 2, and 500 mg Day 3+) ≥ 45 kg (200 mg Day 1, 400 mg Day 2, and 800 mg Day 3+)

Investigational medicinal product name

Dexamethasone (n=19 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of dexamethasone administered was 10 mg/m^2 per day (or equivalent dose of prednisone), and the dosing schedule was determined by the treating investigator. ALL subjects were permitted to receive dexamethasone and/or vincristine and/or pegasparaginase as a chemotherapy regimen.

Investigational medicinal product name

Vincristine (n=19 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of vincristine administered was 2 mg/m^2 per day; (2 mg max; no more frequently than weekly), and the dosing schedule was determined by the treating investigator. ALL subjects were permitted to receive dexamethasone and/or vincristine and/or pegasparaginase as a chemotherapy regimen.

Investigational medicinal product name

Pegasparaginase (n=13 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of pegasparaginase administered was 2,500 IU/m^2/dose per day (every two weeks), and the dosing schedule was determined by the treating investigator. For those with allergy or intolerance to pegasparaginase, Erwinia asparaginase was acceptable. ALL subjects were permitted to receive dexamethasone and/or vincristine and/or pegasparaginase as a chemotherapy regimen.

Investigational medicinal product name

Cytarabine (n=10 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of cytarabine administered was 1000 mg/m^2 twice per day, and the dosing schedule was determined by the treating investigator. ALL subjects were permitted to receive cytarabine and/or etoposide and/or pegasparaginase as a chemotherapy regimen.

Investigational medicinal product name

Etoposide (n=4 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of etoposide administered was 50 mg/m^2 per day (or 100 mg/m^2 IV daily), and the dosing schedule was determined by the treating investigator. ALL subjects were permitted to receive cytarabine and/or etoposide and/or pegasparaginase as a chemotherapy regimen.

Investigational medicinal product name

Pegasparaginase with the Cytarabine-based regimen (n=3 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of pegasparaginase administered was 2,500 IU/m^2/dose per day (Every 2 weeks), and the dosing schedule was determined by the treating investigator. For those with allergy or intolerance to pegasparaginase, Erwinia asparaginase was acceptable. ALL subjects were permitted to receive cytarabine and/or etoposide and/or pegasparaginase as a chemotherapy regimen.

Acute Myeloid Leukemia (AML)

Arm description

Participants with acute myeloid leukemia (AML)

Arm type

Experimental

Investigational medicinal product name

Venetoclax (n=37 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Dispersible tablet, Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Cytarabine low dose (n= 1 subject)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravascular use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of cytarabine administered was 20 mg/m^2 per day (every two weeks), and the dosing schedule was determined by the treating investigator. AML subjects were permitted to receive cytarabine or azacitidine/decitabine as a chemotherapy regimen.

Investigational medicinal product name

Cytarabine high dose (n= 9 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of cytarabine administered was 1000 mg/m^2 twice per day, and the dosing schedule was determined by the treating investigator. AML subjects were permitted to receive cytarabine or azacitidine/decitabine as a chemotherapy regimen.

Investigational medicinal product name

Azacitidine (n= 19 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for suspension for injection

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of azacitidine administered was 75 mg/m^2 per day, and the dosing schedule was determined by the treating investigator. AML subjects were permitted to receive cytarabine or azacitidine/decitabine as a chemotherapy regimen.

Investigational medicinal product name

Decitabine (n= 5 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of decitabine administered was 20 mg/m^2 per day, and the dosing schedule was determined by the treating investigator. AML subjects were permitted to receive cytarabine or azacitidine/decitabine as a chemotherapy regimen.

Non-Hodgkin Lymphoma (NHL)

Arm description

Participants with non-Hodgkin lymphoma (NHL)

Arm type

Experimental

Investigational medicinal product name

Venetoclax (n=2 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Dispersible tablet, Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Rituximab (n= 1 subject)

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of rituximab administered was 375 mg/m^2 per day (weekly), and the dosing schedule was determined by the treating investigator. NHL subjects were permitted to receive rituximab and/or dexamethasone and/or vincristine as a chemotherapy regimen.

Investigational medicinal product name

Dexamethasone (n= 2 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of dexamethasone administered was 40 mg per day, and the dosing schedule was determined by the treating investigator. NHL subjects were permitted to receive rituximab and/or dexamethasone and/or vincristine as a chemotherapy regimen.

Investigational medicinal product name

Vincristine (n=2 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 4 or after for those with hematologic malignancies. The maximum dose of vincristine administered was 1.5 mg/m^2 per day; (2 mg max; weekly), and the dosing schedule was determined by the treating investigator. NHL subjects were permitted to receive rituximab and/or dexamethasone and/or vincristine as a chemotherapy regimen.

Neuroblastoma (NBL)

Arm description

Participants with neuroblastoma (NBL)

Arm type

Experimental

Investigational medicinal product name

Venetoclax (n=36 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Dispersible tablet, Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Subjects with solid tumors enrolled in Part 1 (Dose Determination) were administered venetoclax orally QD, continuously. Those with solid tumors enrolled in the Part 1 Escalation/De-escalation portion received venetoclax orally QD, continuously or intermittently based on BOIN design and occurrence of DLTs. Results from Part 1 were used to determine venetoclax dosing/regimen for Part 2. Subjects who were < 2 years of age were dosed based on age and those who were 2 years and older were dosed based on weight. 400 mg adult-equivalent target dose: from 2.5 mg Day 1/5 mg Day 2+ for subjects <1 month old to a max of 200 mg Day 1/400 mg Day 2+ for subjects ≥45 kg 600 mg adult-equivalent target dose: from 5 mg Day 1/7.5 mg Day 2+ for subjects <1 month old to a max of 400 mg Day 1/600 mg on Day 2+ for subjects ≥45 kg 800 mg adult-equivalent target dose: from 5 mg Day 1/10 mg Day 2+ for subjects <1 month old to a max of 400 mg Day 1/ 800 mg on Day 2+ for subjects ≥45 kg

Investigational medicinal product name

Cyclophosphamide (n=35 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 3 or after for those with neuroblastoma or solid tumors. The maximum dose of cyclophosphamide administered was 250 mg/m^2 per day (maximum 5 days every 21 days), and the dosing schedule was determined by the treating investigator. NBL subjects were permitted to receive cyclophosphamide and topotecan as a chemotherapy regimen.

Investigational medicinal product name

Topotecan (n=35 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for concentrate and solution for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 3 or after for those with neuroblastoma or solid tumors. The maximum dose of topotecan administered was 0.75 mg/m^2 per day (maximum 5 days every 21 days), and the dosing schedule was determined by the treating investigator. NBL subjects were permitted to receive cyclophosphamide and topotecan as a chemotherapy regimen.

Other Tumors

Arm description

Participants with evidence of BCL-2 expression determined locally in either archived tumor tissue or tumor tissue available at relapse were included in the Other Tumors group. Exception: those with TCF3- HLF ALL enrolled in this group were not required to have evidence of BCL-2 expression. The types of primary cancer for the Other Tumors group included Secondary Myelodysplastic Syndrome, Myeloid MPAL, Secondary AML, Secondary ALL with TCF3/HLF Fusion, and Mixed Phenotype Acute Leukemia (T/Myeloid).

Arm type

Experimental

Investigational medicinal product name

Venetoclax (n=11 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Dispersible tablet, Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Solid Tumors

Arm description

The Solid Tumors group included participants with solid tumors other than neuroblastoma (except for 2 neuroblastoma participants who had received alternative chemotherapy regimens) with evidence of BCL-2 expression determined locally in either archived tumor tissue or tumor tissue available at relapse. The types of primary cancer for the Solid Tumors group included Wilms Tumor, Gastrointestinal Stromal Tumor, Synovial Sarcoma, Alveolar Rhabdomyosarcoma, Biliary Tract Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Ewing’s Sarcoma, Desmoplastic Small Round Cell Tumor, NRSTS (BCOR), and Evans Tumor.

Arm type

Experimental

Investigational medicinal product name

Venetoclax (n=23 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Dispersible tablet, Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Cyclophosphamide (n=16 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 3 or after for those with neuroblastoma or solid tumors. The maximum dose of cyclophosphamide administered was 250 mg/m^2 per day (maximum 5 days every 21 days), and the dosing schedule was determined by the treating investigator. Subjects in the Solid Tumors group were permitted to receive cyclophosphamide and/or topotecan as a chemotherapy regimen.

Investigational medicinal product name

Topotecan (n=19 subjects)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for concentrate and solution for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Chemotherapy was added to venetoclax beginning on Day 3 or after for those with neuroblastoma or solid tumors. The maximum dose of topotecan administered was 0.75 mg/m^2 per day (maximum 5 days every 21 days), and the dosing schedule was determined by the treating investigator. Subjects in the Solid Tumors group were permitted to receive cyclophosphamide and/or topotecan as a chemotherapy regimen.

Number of subjects in period 1	Acute Lymphoblastic Leukemia (ALL)	Acute Myeloid Leukemia (AML)	Non-Hodgkin Lymphoma (NHL)	Neuroblastoma (NBL)	Other Tumors	Solid Tumors
Started	31	37	2	36	11	23
Completed	0	1	0	2	0	1
Not completed	31	36	2	34	11	22
Physician decision	3	5	-	8	2	2
Adverse event, non-fatal	5	1	-	2	-	1
Death	1	-	-	2	-	1
Other, not specified	3	-	-	3	-	1
Progressive disease	9	25	1	18	6	17
Withdrew consent	2	1	-	1	-	-
Transplant	8	4	1	-	3	-

Baseline characteristics

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Reporting group title

Acute Lymphoblastic Leukemia (ALL)

Reporting group description

Participants with acute lymphoblastic leukemia (ALL)

Reporting group title

Acute Myeloid Leukemia (AML)

Reporting group description

Participants with acute myeloid leukemia (AML)

Reporting group title

Non-Hodgkin Lymphoma (NHL)

Reporting group description

Participants with non-Hodgkin lymphoma (NHL)

Reporting group title

Neuroblastoma (NBL)

Reporting group description

Participants with neuroblastoma (NBL)

Reporting group title

Other Tumors

Reporting group description

Reporting group title

Solid Tumors

Reporting group description

Reporting group values	Acute Lymphoblastic Leukemia (ALL)	Acute Myeloid Leukemia (AML)	Non-Hodgkin Lymphoma (NHL)	Neuroblastoma (NBL)	Other Tumors	Solid Tumors	Total
Number of subjects	31	37	2	36	11	23	140
Age categorical
Units: Subjects
Age continuous
Units: years
median (full range (min-max))	9.0 (0 to 25)	6.0 (0 to 17)	12.0 (3 to 21)	8.0 (1 to 17)	10.0 (5 to 19)	16.0 (3 to 24)	-
Gender categorical
Units: Subjects
Female	15	19	2	14	5	9	64
Male	16	18	0	22	6	14	76

End points

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Reporting group title

Acute Lymphoblastic Leukemia (ALL)

Reporting group description

Participants with acute lymphoblastic leukemia (ALL)

Reporting group title

Acute Myeloid Leukemia (AML)

Reporting group description

Participants with acute myeloid leukemia (AML)

Reporting group title

Non-Hodgkin Lymphoma (NHL)

Reporting group description

Participants with non-Hodgkin lymphoma (NHL)

Reporting group title

Neuroblastoma (NBL)

Reporting group description

Participants with neuroblastoma (NBL)

Reporting group title

Other Tumors

Reporting group description

Reporting group title

Solid Tumors

Reporting group description

Subject analysis set title

400 mg venetoclax (pharmacokinetic sampling)

Subject analysis set type

Full analysis

Subject analysis set description

All subjects who were treated with 400 mg venetoclax with viable pharmacokinetic data at Week 2, Day 8

Subject analysis set title

800 mg venetoclax (pharmacokinetic sampling)

Subject analysis set type

Full analysis

Subject analysis set description

All subjects who were treated with 800 mg venetoclax with viable pharmacokinetic data at Week 2, Day 8

Subject analysis set title

Part 1 AML MRD analysis

Subject analysis set type

Full analysis

Subject analysis set description

Part 1 participants with acute myeloid leukemia (AML)

Subject analysis set title

Part 2 AML MRD analysis

Subject analysis set type

Full analysis

Subject analysis set description

Part 2 participants with acute myeloid leukemia (AML)

Subject analysis set title

Part 1 ALL MRD analysis

Subject analysis set type

Full analysis

Subject analysis set description

Part 1 participants with acute lymphoblastic leukemia (ALL)

Subject analysis set title

Part 2 ALL MRD analysis

Subject analysis set type

Full analysis

Subject analysis set description

Part 2 participants with acute lymphoblastic leukemia (ALL)

Primary: Number of Participants With Adverse Events

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End point title

Number of Participants With Adverse Events ^[1]

End point description

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

End point type

Primary

End point timeframe

From the first dose of study drug to 30 days after last dose, up to 170, 312, 111, 385, 299, and 1168 days for the ALL, AML, NHL, NBL, other tumors, and solid tumors groups, respectively

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: Descriptive data are summarized for this end point per protocol.

End point values	Acute Lymphoblastic Leukemia (ALL)	Acute Myeloid Leukemia (AML)	Non-Hodgkin Lymphoma (NHL)	Neuroblastoma (NBL)	Other Tumors	Solid Tumors
Number of subjects analysed	31 ^[2]	37 ^[3]	2 ^[4]	36 ^[5]	11 ^[6]	23 ^[7]
Units: number of participants
Any TEAE	31	37	2	36	11	23
TESAE	24	28	1	34	5	18

Notes
[2] - Participants who received at least one dose of study drug
[3] - Participants who received at least one dose of study drug
[4] - Participants who received at least one dose of study drug
[5] - Participants who received at least one dose of study drug
[6] - Participants who received at least one dose of study drug
[7] - Participants who received at least one dose of study drug

No statistical analyses for this end point

Primary: Part 1: Number of Participants With Dose Limiting Toxicities (DLT) of Venetoclax Monotherapy

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End point title

Part 1: Number of Participants With Dose Limiting Toxicities (DLT) of Venetoclax Monotherapy ^[8]

End point description

DLT criteria for ALL/AML: ●Any Grade 5 toxicity ●Grade 4 neutropenia or thrombocytopenia lasting ≥42 days from start of venetoclax administration in absence of evidence of active leukemia ●Any Grade ≥3 non-hematologic toxicity not clearly resulting from the underlying leukemia (with exceptions noted in Section 6.1.8.1 of study protocol) DLT criteria for NHL/NBL/other solid tumors: ●Any Grade 5 toxicity ●Any Grade 3 or 4 non-hematologic adverse event not clearly related to the underlying tumor (with exceptions noted in Section 6.1.8.1 of the study protocol) DLT criteria for subjects with adequate bone marrow function at study entry: ●Any Grade 5 hematologic toxicity ●Grade 4 febrile neutropenia ●Grade 4 anemia ●Neutropenia or thrombocytopenia resulting in a delay of > 14 days in meeting criteria (ANC ≥1000/mm3 and platelets ≥75,000/µL) to start a subsequent cycle in the absence of disease in the bone marrow

End point type

Primary

End point timeframe

During the first 21 days of venetoclax monotherapy in Part 1 (Dose Determination) or during Cycle 1 of combination therapy (venetoclax plus chemotherapy) in Part 1 (Dose Escalation/De-Escalation)

Notes
[8] - 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: Descriptive data are summarized for this end point per protocol.

End point values	Acute Lymphoblastic Leukemia (ALL)	Acute Myeloid Leukemia (AML)	Non-Hodgkin Lymphoma (NHL)	Neuroblastoma (NBL)	Other Tumors	Solid Tumors
Number of subjects analysed	31 ^[9]	37 ^[10]	2 ^[11]	36 ^[12]	11 ^[13]	23 ^[14]
Units: number of participants	2	1	1	4	1	3

Notes
[9] - Participants who received at least one dose of study drug
[10] - Participants who received at least one dose of study drug
[11] - Participants who received at least one dose of study drug
[12] - Participants who received at least one dose of study drug
[13] - Participants who received at least one dose of study drug
[14] - Participants who received at least one dose of study drug

No statistical analyses for this end point

Primary: Part 1: Maximum Observed Plasma Concentration (Cmax) of Venetoclax (Week 2, Day 8) of Venetoclax (Week 2, Day 8)

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End point title

Part 1: Maximum Observed Plasma Concentration (Cmax) of Venetoclax (Week 2, Day 8) of Venetoclax (Week 2, Day 8) ^[15]

End point description

Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.

End point type

Primary

End point timeframe

0 hrs pre-dose and 2, 4, 6, and 8 hours post-dose at Week 2, Day 8

Notes
[15] - 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: Descriptive data are summarized for this end point per protocol.

End point values	400 mg venetoclax (pharmacokinetic sampling)	800 mg venetoclax (pharmacokinetic sampling)
Number of subjects analysed	31 ^[16]	102 ^[17]
Units: µg/mL
arithmetic mean (standard deviation)	1.91 ( 1.38 )	2.28 ( 1.66 )

Notes
[16] - Participants who received at least one dose of study drug with pharmacokinetic data
[17] - Participants who received at least one dose of study drug with pharmacokinetic data

No statistical analyses for this end point

Primary: Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax (Week 2, Day 8)

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End point title

Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax (Week 2, Day 8) ^[18]

End point description

Tmax is the the time at which the maximum plasma concentration (Cmax) is observed.

End point type

Primary

End point timeframe

0 hrs pre-dose and 2, 4, 6, and 8 hours post-dose at Week 2, Day 8

Notes
[18] - 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: Descriptive data are summarized for this end point per protocol.

End point values	400 mg venetoclax (pharmacokinetic sampling)	800 mg venetoclax (pharmacokinetic sampling)
Number of subjects analysed	31 ^[19]	102 ^[20]
Units: hours
median (full range (min-max))	5.95 (2.25 to 8.05)	4.37 (0 to 8.58)

Notes
[19] - Participants who received at least one dose of study drug with pharmacokinetic data
[20] - Participants who received at least one dose of study drug with pharmacokinetic data

No statistical analyses for this end point

Primary: Part 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to 24 Hours (AUC0-24) of Venetoclax (Week 2, Day 8)

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End point title

Part 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to 24 Hours (AUC0-24) of Venetoclax (Week 2, Day 8) ^[21]

End point description

AUC is a measure of how long and how much drug is present in the body after dosing.

End point type

Primary

End point timeframe

0 hrs pre-dose and 2, 4, 6, 8, and 24 hours post-dose at Week 2, Day 8

Notes
[21] - 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: Descriptive data are summarized for this end point per protocol.

End point values	400 mg venetoclax (pharmacokinetic sampling)	800 mg venetoclax (pharmacokinetic sampling)
Number of subjects analysed	31 ^[22]	100 ^[23]
Units: µg•h/mL
arithmetic mean (standard deviation)	27.5 ( 24.4 )	31.9 ( 25.4 )

Notes
[22] - Participants who received at least one dose of study drug with pharmacokinetic data
[23] - Participants who received at least one dose of study drug with pharmacokinetic data

No statistical analyses for this end point

Primary: Part 1: Apparent clearance (CL/F) of venetoclax (Week 2, Day 8)

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End point title

Part 1: Apparent clearance (CL/F) of venetoclax (Week 2, Day 8) ^[24]

End point description

Clearance is a quantitative measure of the rate at which a drug substance is removed from the body.

End point type

Primary

End point timeframe

0 hrs pre-dose and 2, 4, 6, and 8 hours post-dose at Week 2, Day 8

Notes
[24] - 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: Descriptive data are summarized for this end point per protocol.

End point values	400 mg venetoclax (pharmacokinetic sampling)	800 mg venetoclax (pharmacokinetic sampling)
Number of subjects analysed	31 ^[25]	100 ^[26]
Units: L/hour
arithmetic mean (standard deviation)	25.2 ( 17.9 )	44.1 ( 37.3 )

Notes
[25] - Participants who received at least one dose of study drug with pharmacokinetic data
[26] - Participants who received at least one dose of study drug with pharmacokinetic data

No statistical analyses for this end point

Secondary: Objective Response Rate

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End point title

Objective Response Rate ^[27]

End point description

Objective response rate (ORR) is defined as the percentage of participants who achieved a complete response (CR), complete response with incomplete marrow recovery (CRi), complete response without platelet recovery (CRp) or partial response (PR) as best response for participants with ALL or AML; CR or PR as best response for participants with NHL and solid tumors; and CR or PR or minor response (MR) as best response for participants with NBL. Participants who did not achieve an objective response per the above criteria, including those with incomplete or missing data, were considered to be non-responders in the calculation of objective response rate.

End point type

Secondary

End point timeframe

Response was assessed at each post-baseline visit; overall median time on follow-up was 946 days

Notes
[27] - 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 the 11 subjects with other tumors in the exploratory cohort, which were included in the Other Tumor analysis group, no efficacy analysis was performed due to the many different tumor types enrolled.

End point values	Acute Lymphoblastic Leukemia (ALL)	Acute Myeloid Leukemia (AML)	Non-Hodgkin Lymphoma (NHL)	Neuroblastoma (NBL)	Solid Tumors
Number of subjects analysed	31 ^[28]	37 ^[29]	2 ^[30]	36 ^[31]	23 ^[32]
Units: percentage of participants
number (confidence interval 95%)	41.9 (24.5 to 60.9)	24.3 (11.8 to 41.2)	50.0 (1.3 to 98.7)	30.6 (16.3 to 48.1)	21.7 (7.5 to 43.7)

Notes
[28] - Participants who received at least one dose of study drug
[29] - Participants who received at least one dose of study drug
[30] - Participants who received at least one dose of study drug
[31] - Participants who received at least one dose of study drug
[32] - Participants who received at least one dose of study drug

No statistical analyses for this end point

Secondary: Complete Response (CR) Rate

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End point title

Complete Response (CR) Rate ^[33]

End point description

Complete response rate (CRR) is defined as the percentage of participants who achieved a complete response (CR), complete response with incomplete marrow recovery (CRi), or complete response without platelet recovery (CRp) as best response for ALL and AML, and the percentage of participants who achieved a CR as best response for NHL, neuroblastoma, and solid tumors. Participants who did not achieve any component of CR, including those with incomplete or missing data, were considered as non-responders in the calculation of CR rate.

End point type

Secondary

End point timeframe

Response was assessed at each post-baseline visit; overall median time on follow-up was 946 days

Notes
[33] - 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 the 11 subjects with other tumors in the exploratory cohort, which were included in the Other Tumor analysis group, no efficacy analysis was performed due to the many different tumor types enrolled.

End point values	Acute Lymphoblastic Leukemia (ALL)	Acute Myeloid Leukemia (AML)	Non-Hodgkin Lymphoma (NHL)	Neuroblastoma (NBL)	Solid Tumors
Number of subjects analysed	31 ^[34]	37 ^[35]	2 ^[36]	36 ^[37]	23 ^[38]
Units: percentage of participants
number (confidence interval 95%)	41.9 (24.5 to 60.9)	16.2 (6.2 to 32.0)	0 (0.0 to 84.2)	22.2 (10.1 to 39.2)	4.3 (0.1 to 21.9)

Notes
[34] - Participants who received at least one dose of study drug
[35] - Participants who received at least one dose of study drug
[36] - Participants who received at least one dose of study drug
[37] - Participants who received at least one dose of study drug
[38] - Participants who received at least one dose of study drug

No statistical analyses for this end point

Secondary: Partial Response Rate

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End point title

Partial Response Rate ^[39]

End point description

Partial response rate (PRR) is defined as the percentage of participants who achieved a PR as best response. Participants who did not achieve a PR as best response, including those with incomplete or missing data, were considered as non-responders in the calculation of PR rate.

End point type

Secondary

End point timeframe

Response was assessed at each post-baseline visit; overall median time on follow-up was 946 days

Notes
[39] - 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 the 11 subjects with other tumors in the exploratory cohort, which were included in the Other Tumor analysis group, no efficacy analysis was performed due to the many different tumor types enrolled.

End point values	Acute Lymphoblastic Leukemia (ALL)	Acute Myeloid Leukemia (AML)	Non-Hodgkin Lymphoma (NHL)	Neuroblastoma (NBL)	Solid Tumors
Number of subjects analysed	31 ^[40]	37 ^[41]	2 ^[42]	36 ^[43]	23 ^[44]
Units: percentage of participants
number (confidence interval 95%)	0 (0.0 to 11.2)	8.1 (1.7 to 21.9)	50.0 (1.3 to 98.7)	8.3 (1.8 to 22.5)	17.4 (5.0 to 38.8)

Notes
[40] - Participants who received at least one dose of study drug
[41] - Participants who received at least one dose of study drug
[42] - Participants who received at least one dose of study drug
[43] - Participants who received at least one dose of study drug
[44] - Participants who received at least one dose of study drug

No statistical analyses for this end point

Secondary: Progression-free Survival (PFS)

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End point title

Progression-free Survival (PFS) ^[45]

End point description

Progression-free survival (PFS) is defined as the number of days from the date of the first dose of study drug to the date of earliest disease progression or death. All events of disease progression were included regardless of whether the event occurred while the participant was taking study drug or had previously discontinued the study drug. If the participant had not experienced disease progression or death, their data were censored at the date of the last disease assessment. Data for those without any disease assessments performed after the first dose of study drug were censored at the date of the first dose of study drug plus 1 day. PFS was analyzed by Kaplan-Meier methodology. In the table below, 999 and 99999 indicate not calculable/estimable due to low number of participants with events.

End point type

Secondary

End point timeframe

Overall median time on follow-up was 946 days

Notes
[45] - 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 the 11 subjects with other tumors in the exploratory cohort, which were included in the Other Tumor analysis group, no efficacy analysis was performed due to the many different tumor types enrolled.

End point values	Acute Lymphoblastic Leukemia (ALL)	Acute Myeloid Leukemia (AML)	Non-Hodgkin Lymphoma (NHL)	Neuroblastoma (NBL)	Solid Tumors
Number of subjects analysed	31 ^[46]	37 ^[47]	2 ^[48]	36 ^[49]	23 ^[50]
Units: days
median (confidence interval 95%)	28.0 (22.0 to 95.0)	42.0 (31.0 to 76.0)	999 (14.0 to 99999)	114.0 (58.0 to 224.0)	88.0 (49.0 to 245.0)

Notes
[46] - Participants who received at least one dose of study drug
[47] - Participants who received at least one dose of study drug
[48] - Participants who received at least one dose of study drug
[49] - Participants who received at least one dose of study drug
[50] - Participants who received at least one dose of study drug

No statistical analyses for this end point

Secondary: Overall Survival

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End point title

Overall Survival ^[51]

End point description

Overall survival (OS) is defined as the number of days from the date of the first dose of study drug to the date of death. Data from participants that were alive at the time of analysis were censored at the date of last study visit or the last known date the participant was alive, whichever was later. OS was analyzed by Kaplan-Meier methodology. In the table below, 999 and 99999 indicate not calculable/estimable due to low number of participants with events.

End point type

Secondary

End point timeframe

Overall median time on follow-up was 946 days

Notes
[51] - 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 the 11 subjects with other tumors in the exploratory cohort, which were included in the Other Tumor analysis group, no efficacy analysis was performed due to the many different tumor types enrolled.

End point values	Acute Lymphoblastic Leukemia (ALL)	Acute Myeloid Leukemia (AML)	Non-Hodgkin Lymphoma (NHL)	Neuroblastoma (NBL)	Solid Tumors
Number of subjects analysed	31 ^[52]	37 ^[53]	2 ^[54]	36 ^[55]	23 ^[56]
Units: days
median (confidence interval 95%)	118.0 (75.0 to 290.0)	110.0 (76.0 to 216.0)	999 (31.0 to 99999)	431.0 (195.0 to 721.0)	180.0 (107.0 to 714.0)

Notes
[52] - Participants who received at least one dose of study drug
[53] - Participants who received at least one dose of study drug
[54] - Participants who received at least one dose of study drug
[55] - Participants who received at least one dose of study drug
[56] - Participants who received at least one dose of study drug

No statistical analyses for this end point

Secondary: Minimal Residual Disease (MRD) negativity rate

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End point title

Minimal Residual Disease (MRD) negativity rate

End point description

MRD negativity rate is defined as the percentage of participants who achieved MRD negativity. MRD status that was collected after start of post study-treatment cancer therapy, if applicable, was included in the analyses. Participants who did not achieve MRD negativity, including those without MRD assessment, were considered to be non-responders in the calculation of MRD negativity status.

End point type

Secondary

End point timeframe

Overall median time on follow-up was 946 days

End point values	Part 1 AML MRD analysis	Part 2 AML MRD analysis	Part 1 ALL MRD analysis	Part 2 ALL MRD analysis
Number of subjects analysed	10 ^[57]	27 ^[58]	5 ^[59]	26 ^[60]
Units: percentage of participants
number (confidence interval 95%)	0 (0.0 to 30.8)	7.4 (0.9 to 24.3)	40.0 (5.3 to 85.3)	26.9 (11.6 to 47.8)

Notes
[57] - Participants with AML who received at least one dose of study drug with available data
[58] - Participants with AML who received at least one dose of study drug with available data
[59] - Participants with ALL who received at least one dose of study drug with available data
[60] - Participants with ALL who received at least one dose of study drug with available data

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Treatment-emergent adverse events and serious adverse events collected from 1st dose of study drug to 30 days after last dose, up to 170, 312, 111, 385, 299, and 1168 days for the ALL, AML, NHL, NBL, other tumors, and solid tumors groups, respectively.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

ALL venetoclax 800 mg

Reporting group description

Participants with acute lymphoblastic leukemia (ALL) who received 800 mg of venetoclax

Reporting group title

AML venetoclax 800 mg

Reporting group description

Participants with with acute myeloid leukemia (AML) who received 800 mg of venetoclax

Reporting group title

NHL venetoclax 800 mg

Reporting group description

Participants with non-Hodgkin lymphoma (NHL) who received 800 mg of venetoclax

Reporting group title

NBL venetoclax 800 mg

Reporting group description

Participants with neuroblastoma (NBL) who received 800 mg of venetoclax

Reporting group title

Solid Tumors Part 2 Expansion

Reporting group description

Participants with solid tumors other than neuroblastoma (with the exception of 2 participants who had received alternative chemotherapies) with evidence of BCL-2 expression determined locally in either archived tumor tissue or tumor tissue available at relapse treated with venetoclax during Part 2 of the study. Exception: those with TCF3- HLF ALL enrolled in this group were not required to have evidence of BCL-2 expression. The types of primary cancer for the solid tumors group include Wilms Tumor, Gastrointestinal Stromal Tumor, Synovial Sarcoma, Alveolar Rhabdomyosarcoma, Biliary Tract Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Ewing’s Sarcoma, Desmoplastic Small Round Cell Tumor, NRSTS (BCOR), and Evans Tumor.

Reporting group title

Solid tumors venetoclax 400 mg

Reporting group description

Participants with solid tumors other than neuroblastoma (with the exception of 2 participants who had received alternative chemotherapies) with evidence of BCL-2 expression determined locally in either archived tumor tissue or tumor tissue available at relapse treated with 400 mg of venetoclax. Exception: those with TCF3- HLF ALL enrolled in this group were not required to have evidence of BCL-2 expression. The types of primary cancer for the solid tumors group include Wilms Tumor, Gastrointestinal Stromal Tumor, Synovial Sarcoma, Alveolar Rhabdomyosarcoma, Biliary Tract Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Ewing’s Sarcoma, Desmoplastic Small Round Cell Tumor, NRSTS (BCOR), and Evans Tumor.

Reporting group title

Solid tumors venetoclax 400 mg intermittent

Reporting group description

Participants with solid tumors other than neuroblastoma (with the exception of 2 participants who had received alternative chemotherapies) with evidence of BCL-2 expression determined locally in either archived tumor tissue or tumor tissue available at relapse treated intermittently with 400 mg of venetoclax. Exception: those with TCF3- HLF ALL enrolled in this group were not required to have evidence of BCL-2 expression. The types of primary cancer for the solid tumors group include Wilms Tumor, Gastrointestinal Stromal Tumor, Synovial Sarcoma, Alveolar Rhabdomyosarcoma, Biliary Tract Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Ewing’s Sarcoma, Desmoplastic Small Round Cell Tumor, NRSTS (BCOR), and Evans Tumor.

Reporting group title

Solid tumors venetoclax 800 mg intermittent

Reporting group description

Participants with solid tumors other than neuroblastoma (with the exception of 2 participants who had received alternative chemotherapies) with evidence of BCL-2 expression determined locally in either archived tumor tissue or tumor tissue available at relapse treated intermittently with 800 mg of venetoclax. Exception: those with TCF3- HLF ALL enrolled in this group were not required to have evidence of BCL-2 expression. The types of primary cancer for the solid tumors group include Wilms Tumor, Gastrointestinal Stromal Tumor, Synovial Sarcoma, Alveolar Rhabdomyosarcoma, Biliary Tract Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Ewing’s Sarcoma, Desmoplastic Small Round Cell Tumor, NRSTS (BCOR), and Evans Tumor.

Reporting group title

Solid tumors Part 1 Dose Determination

Reporting group description

Participants with solid tumors other than neuroblastoma (with the exception of 2 participants who had received alternative chemotherapies) with evidence of BCL-2 expression determined locally in either archived tumor tissue or tumor tissue available at relapse treated with venetoclax during Part 1 of the study. Exception: those with TCF3- HLF ALL enrolled in this group were not required to have evidence of BCL-2 expression. The types of primary cancer for the solid tumors group include Wilms Tumor, Gastrointestinal Stromal Tumor, Synovial Sarcoma, Alveolar Rhabdomyosarcoma, Biliary Tract Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Ewing’s Sarcoma, Desmoplastic Small Round Cell Tumor, NRSTS (BCOR), and Evans Tumor.

Reporting group title

Other tumors venetoclax 800 mg

Reporting group description

Participants with evidence of BCL-2 expression determined locally in either archived tumor tissue or tumor tissue available at relapse who were treated with 800 mg of venetoclax. Exception: those with TCF3- HLF ALL enrolled in this group were not required to have evidence of BCL-2 expression. The types of primary cancer for the other tumors group include Myelodysplastic Syndrome, Myeloid MPAL, AML, ALL with TCF3/HLF Fusion, and Mixed Phenotype Acute Leukemia (T/Myeloid).

Serious adverse events	ALL venetoclax 800 mg	AML venetoclax 800 mg	NHL venetoclax 800 mg	NBL venetoclax 800 mg	Solid Tumors Part 2 Expansion	Solid tumors venetoclax 400 mg	Solid tumors venetoclax 400 mg intermittent	Solid tumors venetoclax 800 mg intermittent	Solid tumors Part 1 Dose Determination	Other tumors venetoclax 800 mg
Total subjects affected by serious adverse events
subjects affected / exposed	24 / 31 (77.42%)	28 / 37 (75.68%)	1 / 2 (50.00%)	34 / 36 (94.44%)	7 / 8 (87.50%)	1 / 2 (50.00%)	4 / 4 (100.00%)	3 / 5 (60.00%)	3 / 4 (75.00%)	5 / 11 (45.45%)
number of deaths (all causes)	23	31	1	20	5	1	3	5	2	7
number of deaths resulting from adverse events	6	3	0	1	1	0	0	0	1	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NEOPLASM
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MALIGNANT NEOPLASM PROGRESSION
subjects affected / exposed	2 / 31 (6.45%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
LEUKAEMIA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
TUMOUR PAIN
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
HYPOTENSION
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	4 / 36 (11.11%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	3 / 4	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPERTENSION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
THROMBOPHLEBITIS
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
THROMBOSIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
DISEASE PROGRESSION
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PYREXIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	3 / 36 (8.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MULTIPLE ORGAN DYSFUNCTION SYNDROME
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	2 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	1 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
FACIAL PAIN
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NON-CARDIAC CHEST PAIN
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
HYPERSENSITIVITY
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CYTOKINE RELEASE SYNDROME
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
EPISTAXIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOXIA
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	3 / 3	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
LUNG DISORDER
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMOTHORAX
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PULMONARY HAEMORRHAGE
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PULMONARY OEDEMA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RESPIRATORY FAILURE
subjects affected / exposed	2 / 31 (6.45%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BLOOD BILIRUBIN INCREASED
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NEUTROPHIL COUNT DECREASED
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INTERNATIONAL NORMALISED RATIO INCREASED
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PLATELET COUNT DECREASED
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	3 / 36 (8.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	4 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
WHITE BLOOD CELL COUNT DECREASED
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
INFUSION RELATED REACTION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CHEMICAL PERITONITIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
POST PROCEDURAL HAEMORRHAGE
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
CARDIAC FAILURE
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PERICARDIAL EFFUSION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
SINUS TACHYCARDIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
NEURALGIA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NEUROTOXICITY
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SEIZURE
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SPINAL CORD COMPRESSION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SYNCOPE
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
subjects affected / exposed	13 / 31 (41.94%)	18 / 37 (48.65%)	0 / 2 (0.00%)	25 / 36 (69.44%)	5 / 8 (62.50%)	1 / 2 (50.00%)	4 / 4 (100.00%)	0 / 5 (0.00%)	3 / 4 (75.00%)	3 / 11 (27.27%)
occurrences causally related to treatment / all	28 / 34	17 / 38	0 / 0	55 / 61	8 / 12	2 / 2	6 / 6	0 / 0	1 / 6	5 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ANAEMIA
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	4 / 36 (11.11%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	5 / 5	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DISSEMINATED INTRAVASCULAR COAGULATION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
FEBRILE BONE MARROW APLASIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NEUTROPENIA
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
ABDOMINAL PAIN
subjects affected / exposed	2 / 31 (6.45%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COLITIS
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ASCITES
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DIARRHOEA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
STOMATITIS
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PROCTALGIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NAUSEA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VOMITING
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
VENOOCCLUSIVE LIVER DISEASE
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPERBILIRUBINAEMIA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HEPATOSPLENOMEGALY
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
ACUTE FEBRILE NEUTROPHILIC DERMATOSIS
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NEUTROPHILIC PANNICULITIS
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SKIN ULCER
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
ACUTE KIDNEY INJURY
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HAEMATURIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CYSTITIS HAEMORRHAGIC
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
ADRENAL INSUFFICIENCY
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BACK PAIN
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
FLANK PAIN
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BONE PAIN
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MUSCULAR WEAKNESS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PAIN IN JAW
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PAIN IN EXTREMITY
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MUSCULOSKELETAL PAIN
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
ASPERGILLUS INFECTION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
APPENDICITIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ABSCESS LIMB
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ATYPICAL MYCOBACTERIAL PNEUMONIA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BACTERAEMIA
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 11 (18.18%)
occurrences causally related to treatment / all	0 / 0	2 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BACTERIAL INFECTION
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BRONCHOPULMONARY ASPERGILLOSIS
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CELLULITIS
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CLOSTRIDIAL INFECTION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CLOSTRIDIUM COLITIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CLOSTRIDIUM DIFFICILE COLITIS
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CLOSTRIDIUM DIFFICILE INFECTION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CORYNEBACTERIUM INFECTION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DEVICE RELATED INFECTION
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ENTEROCOCCAL BACTERAEMIA
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ENTEROCOCCAL INFECTION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ENTEROCOCCAL SEPSIS
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ENTEROCOLITIS INFECTIOUS
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ESCHERICHIA INFECTION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ESCHERICHIA SEPSIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
KLEBSIELLA INFECTION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INFLUENZA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INFECTION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
FUNGAL INFECTION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
FOLLICULITIS
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NECROTISING FASCIITIS
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NASOPHARYNGITIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MUCORMYCOSIS
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
METAPNEUMOVIRUS INFECTION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MENINGITIS
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NOROVIRUS INFECTION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
OTITIS MEDIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PARAINFLUENZAE VIRUS INFECTION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA FUNGAL
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA
subjects affected / exposed	3 / 31 (9.68%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	3 / 6	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PSEUDOMONAL BACTERAEMIA
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RHINOVIRUS INFECTION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SEPSIS
subjects affected / exposed	5 / 31 (16.13%)	2 / 37 (5.41%)	1 / 2 (50.00%)	3 / 36 (8.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	2 / 5	1 / 2	0 / 1	3 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SEPTIC SHOCK
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SERRATIA SEPSIS
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
STOMA SITE INFECTION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
STAPHYLOCOCCAL INFECTION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
STAPHYLOCOCCAL BACTERAEMIA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SOFT TISSUE INFECTION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VULVITIS
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VASCULAR DEVICE INFECTION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 11 (18.18%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VARICELLA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
DECREASED APPETITE
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DEHYDRATION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPERGLYCAEMIA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOCALCAEMIA
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOKALAEMIA
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOPHOSPHATAEMIA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
METABOLIC ACIDOSIS
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	ALL venetoclax 800 mg	AML venetoclax 800 mg	NHL venetoclax 800 mg	NBL venetoclax 800 mg	Solid Tumors Part 2 Expansion	Solid tumors venetoclax 400 mg	Solid tumors venetoclax 400 mg intermittent	Solid tumors venetoclax 800 mg intermittent	Solid tumors Part 1 Dose Determination	Other tumors venetoclax 800 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	31 / 31 (100.00%)	36 / 37 (97.30%)	2 / 2 (100.00%)	36 / 36 (100.00%)	7 / 8 (87.50%)	2 / 2 (100.00%)	4 / 4 (100.00%)	5 / 5 (100.00%)	4 / 4 (100.00%)	11 / 11 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR PAIN
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	0	0	1	0	0	0	0	0	0
SKIN PAPILLOMA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Vascular disorders
FLUSHING
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0
ORTHOSTATIC HYPOTENSION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
HYPOTENSION
subjects affected / exposed	5 / 31 (16.13%)	10 / 37 (27.03%)	0 / 2 (0.00%)	5 / 36 (13.89%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	3 / 11 (27.27%)
occurrences all number	6	15	0	5	0	0	0	1	0	3
HYPERTENSION
subjects affected / exposed	8 / 31 (25.81%)	8 / 37 (21.62%)	1 / 2 (50.00%)	4 / 36 (11.11%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	1 / 11 (9.09%)
occurrences all number	11	10	1	4	1	0	0	1	1	1
HAEMATOMA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	1	0	0	0	0	0	1
VENOUS HAEMORRHAGE
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
General disorders and administration site conditions
CATHETER SITE HAEMORRHAGE
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
CATHETER SITE IRRITATION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
CHEST PAIN
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
ASTHENIA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 11 (18.18%)
occurrences all number	1	0	0	4	0	0	2	0	0	2
AXILLARY PAIN
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
CHILLS
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 4 (50.00%)	0 / 11 (0.00%)
occurrences all number	1	1	0	1	0	0	0	0	2	0
FACE OEDEMA
subjects affected / exposed	1 / 31 (3.23%)	2 / 37 (5.41%)	1 / 2 (50.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	2	1	2	0	0	0	0	0	0
MALAISE
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
LOCALISED OEDEMA
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0
INJECTION SITE BRUISING
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
GENERALISED OEDEMA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	1 / 2 (50.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
GAIT DISTURBANCE
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
FATIGUE
subjects affected / exposed	13 / 31 (41.94%)	7 / 37 (18.92%)	0 / 2 (0.00%)	12 / 36 (33.33%)	2 / 8 (25.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	2 / 5 (40.00%)	1 / 4 (25.00%)	3 / 11 (27.27%)
occurrences all number	15	8	0	19	2	0	1	2	2	4
MEDICAL DEVICE SITE ERYTHEMA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
PUNCTURE SITE PAIN
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
PAIN
subjects affected / exposed	4 / 31 (12.90%)	8 / 37 (21.62%)	0 / 2 (0.00%)	2 / 36 (5.56%)	1 / 8 (12.50%)	1 / 2 (50.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	2 / 11 (18.18%)
occurrences all number	5	8	0	2	1	1	0	1	0	2
OEDEMA PERIPHERAL
subjects affected / exposed	5 / 31 (16.13%)	4 / 37 (10.81%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	6	4	0	0	1	0	0	1	0	0
OEDEMA
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
NON-CARDIAC CHEST PAIN
subjects affected / exposed	0 / 31 (0.00%)	3 / 37 (8.11%)	0 / 2 (0.00%)	2 / 36 (5.56%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	3	0	3	1	0	0	0	0	0
MUCOSAL INFLAMMATION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	3 / 36 (8.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	4	0	0	1	0	0	0
PYREXIA
subjects affected / exposed	7 / 31 (22.58%)	11 / 37 (29.73%)	1 / 2 (50.00%)	7 / 36 (19.44%)	2 / 8 (25.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	1 / 4 (25.00%)	4 / 11 (36.36%)
occurrences all number	7	22	2	8	2	0	0	2	1	5
Immune system disorders
DRUG HYPERSENSITIVITY
subjects affected / exposed	3 / 31 (9.68%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	3	0	0	0	0	0	0	0	0	1
Reproductive system and breast disorders
ERECTILE DYSFUNCTION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
PERINEAL PAIN
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	2
OEDEMA GENITAL
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	4	0	0	0	0	0	0	2	0	0
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
subjects affected / exposed	3 / 31 (9.68%)	2 / 37 (5.41%)	1 / 2 (50.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	5	2	1	2	0	0	1	1	0	0
COUGH
subjects affected / exposed	6 / 31 (19.35%)	6 / 37 (16.22%)	0 / 2 (0.00%)	5 / 36 (13.89%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	2 / 4 (50.00%)	3 / 11 (27.27%)
occurrences all number	9	6	0	6	0	0	1	1	2	3
ATELECTASIS
subjects affected / exposed	0 / 31 (0.00%)	3 / 37 (8.11%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	3	0	0	0	0	0	0	1	0
RHINORRHOEA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	2	0	0	0	0	1	1
TACHYPNOEA
subjects affected / exposed	1 / 31 (3.23%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	2	2	0	0	0	0	0	0	2	0
PULMONARY OEDEMA
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
PLEURAL EFFUSION
subjects affected / exposed	3 / 31 (9.68%)	3 / 37 (8.11%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	3	3	0	1	0	0	0	0	1	0
OROPHARYNGEAL PAIN
subjects affected / exposed	4 / 31 (12.90%)	1 / 37 (2.70%)	0 / 2 (0.00%)	2 / 36 (5.56%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	2 / 11 (18.18%)
occurrences all number	4	1	0	3	1	0	0	0	1	2
NASAL CONGESTION
subjects affected / exposed	0 / 31 (0.00%)	3 / 37 (8.11%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 11 (18.18%)
occurrences all number	0	3	0	0	0	1	0	0	0	2
LARYNGEAL INFLAMMATION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
HYPOXIA
subjects affected / exposed	5 / 31 (16.13%)	7 / 37 (18.92%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	8	8	0	1	0	0	0	0	0	1
EPISTAXIS
subjects affected / exposed	7 / 31 (22.58%)	7 / 37 (18.92%)	0 / 2 (0.00%)	7 / 36 (19.44%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	2 / 11 (18.18%)
occurrences all number	7	7	0	9	0	0	0	2	1	2
Psychiatric disorders
DEPRESSED MOOD
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	1 / 2 (50.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
CONFUSIONAL STATE
subjects affected / exposed	2 / 31 (6.45%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	4	2	0	0	0	0	0	0	0	0
ANXIETY
subjects affected / exposed	5 / 31 (16.13%)	2 / 37 (5.41%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 11 (18.18%)
occurrences all number	5	2	0	1	0	0	1	0	0	2
AGITATION
subjects affected / exposed	2 / 31 (6.45%)	5 / 37 (13.51%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	5	0	1	0	0	0	0	0	0
INITIAL INSOMNIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
IRRITABILITY
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	1	1	0	0	0	0	0
INSOMNIA
subjects affected / exposed	2 / 31 (6.45%)	2 / 37 (5.41%)	1 / 2 (50.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	2	2	1	1	0	0	0	0	0	1
Investigations
ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	4	0	0	0	0	0	0	0	0	1
BLOOD CORTICOTROPHIN DECREASED
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
BLOOD CHOLESTEROL INCREASED
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	0	0	0	0	0	0	2
BLOOD BILIRUBIN INCREASED
subjects affected / exposed	6 / 31 (19.35%)	5 / 37 (13.51%)	0 / 2 (0.00%)	5 / 36 (13.89%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	3 / 11 (27.27%)
occurrences all number	7	8	0	9	0	0	0	2	0	5
BLOOD ALKALINE PHOSPHATASE INCREASED
subjects affected / exposed	3 / 31 (9.68%)	1 / 37 (2.70%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	5	1	0	2	0	0	0	1	0	2
BILIRUBIN CONJUGATED INCREASED
subjects affected / exposed	3 / 31 (9.68%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	4	0	0	0	0	0	0	0	0	0
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	13 / 31 (41.94%)	11 / 37 (29.73%)	1 / 2 (50.00%)	7 / 36 (19.44%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	4 / 11 (36.36%)
occurrences all number	25	11	1	10	0	0	0	0	0	5
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	16 / 31 (51.61%)	11 / 37 (29.73%)	1 / 2 (50.00%)	6 / 36 (16.67%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	4 / 11 (36.36%)
occurrences all number	27	18	1	8	1	0	0	1	0	4
BLOOD CREATININE INCREASED
subjects affected / exposed	2 / 31 (6.45%)	3 / 37 (8.11%)	0 / 2 (0.00%)	3 / 36 (8.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	3	6	0	3	0	0	0	1	0	0
ELECTROCARDIOGRAM QT PROLONGED
subjects affected / exposed	3 / 31 (9.68%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	6	0	0	0	0	0	0	0	0	2
CORTISOL DECREASED
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
CARDIAC MURMUR
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
C-REACTIVE PROTEIN INCREASED
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	1	0	1
BLOOD URIC ACID INCREASED
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	1 / 2 (50.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
BLOOD LACTATE DEHYDROGENASE INCREASED
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	1 / 2 (50.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	1	0	0	0	0	0	0	1
BLOOD FIBRINOGEN DECREASED
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
FLUID BALANCE POSITIVE
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
GAMMA-GLUTAMYLTRANSFERASE INCREASED
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	1 / 2 (50.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	1	2	5	0	0	0	0	0	3
HAEMOGLOBIN INCREASED
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
PROTHROMBIN TIME PROLONGED
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
PLATELET COUNT DECREASED
subjects affected / exposed	6 / 31 (19.35%)	6 / 37 (16.22%)	0 / 2 (0.00%)	15 / 36 (41.67%)	4 / 8 (50.00%)	1 / 2 (50.00%)	1 / 4 (25.00%)	4 / 5 (80.00%)	2 / 4 (50.00%)	7 / 11 (63.64%)
occurrences all number	10	6	0	28	8	1	1	11	4	19
NEUTROPHIL COUNT DECREASED
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	1 / 2 (50.00%)	17 / 36 (47.22%)	3 / 8 (37.50%)	0 / 2 (0.00%)	2 / 4 (50.00%)	3 / 5 (60.00%)	2 / 4 (50.00%)	7 / 11 (63.64%)
occurrences all number	2	2	2	43	3	0	3	7	2	19
LYMPHOCYTE COUNT DECREASED
subjects affected / exposed	4 / 31 (12.90%)	4 / 37 (10.81%)	0 / 2 (0.00%)	16 / 36 (44.44%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 4 (25.00%)	3 / 5 (60.00%)	2 / 4 (50.00%)	10 / 11 (90.91%)
occurrences all number	10	9	0	35	2	0	1	4	4	19
INTERNATIONAL NORMALISED RATIO INCREASED
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	1	0	0	0	0	0	1	0	0
HAPTOGLOBIN DECREASED
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
WHITE BLOOD CELL COUNT INCREASED
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0
WHITE BLOOD CELL COUNT DECREASED
subjects affected / exposed	4 / 31 (12.90%)	5 / 37 (13.51%)	0 / 2 (0.00%)	17 / 36 (47.22%)	1 / 8 (12.50%)	1 / 2 (50.00%)	2 / 4 (50.00%)	4 / 5 (80.00%)	2 / 4 (50.00%)	10 / 11 (90.91%)
occurrences all number	7	10	0	37	2	1	3	7	4	20
WEIGHT INCREASED
subjects affected / exposed	2 / 31 (6.45%)	8 / 37 (21.62%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	6	14	0	1	0	0	0	0	0	0
WEIGHT DECREASED
subjects affected / exposed	2 / 31 (6.45%)	4 / 37 (10.81%)	0 / 2 (0.00%)	6 / 36 (16.67%)	2 / 8 (25.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	2 / 11 (18.18%)
occurrences all number	4	5	0	8	3	0	1	0	2	3
SERUM FERRITIN INCREASED
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Injury, poisoning and procedural complications
ALLERGIC TRANSFUSION REACTION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0
CONTUSION
subjects affected / exposed	1 / 31 (3.23%)	4 / 37 (10.81%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	6	0	2	0	0	0	1	0	2
FALL
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	1	0	1	0	0	0	0	0	2
INFUSION RELATED REACTION
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
PROCEDURAL PAIN
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 11 (9.09%)
occurrences all number	0	3	0	2	0	0	0	0	1	1
PRODUCT USE COMPLAINT
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
STOMA SITE ERYTHEMA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
VASCULAR ACCESS COMPLICATION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0
WOUND SECRETION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Congenital, familial and genetic disorders
FANCONI SYNDROME
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
CONGENITAL POIKILODERMA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Cardiac disorders
BRADYCARDIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0
PALPITATIONS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
PERICARDIAL EFFUSION
subjects affected / exposed	2 / 31 (6.45%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0	0	0
TACHYCARDIA
subjects affected / exposed	1 / 31 (3.23%)	4 / 37 (10.81%)	0 / 2 (0.00%)	4 / 36 (11.11%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 11 (9.09%)
occurrences all number	1	5	0	5	0	0	0	0	3	1
SINUS TACHYCARDIA
subjects affected / exposed	9 / 31 (29.03%)	6 / 37 (16.22%)	0 / 2 (0.00%)	4 / 36 (11.11%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	6 / 11 (54.55%)
occurrences all number	11	11	0	9	2	0	0	0	0	9
SINUS BRADYCARDIA
subjects affected / exposed	2 / 31 (6.45%)	1 / 37 (2.70%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	2	1	0	2	0	0	0	0	0	1
Nervous system disorders
DIZZINESS
subjects affected / exposed	2 / 31 (6.45%)	2 / 37 (5.41%)	0 / 2 (0.00%)	2 / 36 (5.56%)	1 / 8 (12.50%)	1 / 2 (50.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	1 / 11 (9.09%)
occurrences all number	2	2	0	2	1	1	0	1	1	1
DYSGEUSIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0
HEADACHE
subjects affected / exposed	7 / 31 (22.58%)	8 / 37 (21.62%)	0 / 2 (0.00%)	10 / 36 (27.78%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	2 / 4 (50.00%)	4 / 11 (36.36%)
occurrences all number	7	12	0	13	2	0	0	2	3	4
HYPOAESTHESIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0
LETHARGY
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	2 / 8 (25.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 4 (50.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	0	2	0	0	0	3	0
NEUROPATHY PERIPHERAL
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0
PARAESTHESIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	0
TREMOR
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	0	0	0	1	0	0	0	0	0
SPINAL CORD COMPRESSION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0
SOMNOLENCE
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	1	0	0	0	0	0	2	0	0
PERIPHERAL SENSORY NEUROPATHY
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	1 / 2 (50.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	1	0	1	0	0	0	0	0
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
subjects affected / exposed	4 / 31 (12.90%)	3 / 37 (8.11%)	1 / 2 (50.00%)	3 / 36 (8.33%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	3 / 11 (27.27%)
occurrences all number	5	3	1	3	1	0	0	0	0	3
ANAEMIA
subjects affected / exposed	11 / 31 (35.48%)	10 / 37 (27.03%)	1 / 2 (50.00%)	24 / 36 (66.67%)	6 / 8 (75.00%)	1 / 2 (50.00%)	4 / 4 (100.00%)	4 / 5 (80.00%)	2 / 4 (50.00%)	9 / 11 (81.82%)
occurrences all number	14	12	1	41	7	1	6	7	3	14
COAGULOPATHY
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
HYPERLEUKOCYTOSIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
NEUTROPENIA
subjects affected / exposed	4 / 31 (12.90%)	3 / 37 (8.11%)	0 / 2 (0.00%)	10 / 36 (27.78%)	1 / 8 (12.50%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 11 (18.18%)
occurrences all number	8	5	0	19	3	0	2	0	0	8
SPLENOMEGALY
subjects affected / exposed	2 / 31 (6.45%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	2	0	0	0	0	0	0	0	0
THROMBOCYTOPENIA
subjects affected / exposed	11 / 31 (35.48%)	8 / 37 (21.62%)	0 / 2 (0.00%)	9 / 36 (25.00%)	2 / 8 (25.00%)	0 / 2 (0.00%)	3 / 4 (75.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 11 (18.18%)
occurrences all number	14	10	0	21	2	0	14	0	0	2
LYMPHOPENIA
subjects affected / exposed	5 / 31 (16.13%)	5 / 37 (13.51%)	0 / 2 (0.00%)	7 / 36 (19.44%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	9	13	0	13	0	0	2	0	0	3
LYMPHADENOPATHY
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
LEUKOCYTOSIS
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0
LEUKOPENIA
subjects affected / exposed	7 / 31 (22.58%)	5 / 37 (13.51%)	1 / 2 (50.00%)	7 / 36 (19.44%)	1 / 8 (12.50%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	14	11	2	13	1	0	2	0	0	4
Ear and labyrinth disorders
EAR PAIN
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	3 / 36 (8.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	6	0	3	0	0	0	0	0	0
Eye disorders
VISION BLURRED
subjects affected / exposed	3 / 31 (9.68%)	2 / 37 (5.41%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	3	2	0	2	0	0	0	1	1	0
PERIORBITAL OEDEMA
subjects affected / exposed	2 / 31 (6.45%)	3 / 37 (8.11%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	4	0	0	0	0	0	0	0	0
Gastrointestinal disorders
ABDOMINAL PAIN
subjects affected / exposed	11 / 31 (35.48%)	6 / 37 (16.22%)	0 / 2 (0.00%)	7 / 36 (19.44%)	2 / 8 (25.00%)	1 / 2 (50.00%)	2 / 4 (50.00%)	0 / 5 (0.00%)	2 / 4 (50.00%)	1 / 11 (9.09%)
occurrences all number	12	7	0	7	4	1	2	0	4	1
ABDOMINAL DISTENSION
subjects affected / exposed	4 / 31 (12.90%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	4	3	0	0	1	0	0	1	2	0
ABDOMINAL PAIN UPPER
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	0	0	2	1	0	1	0	0	0
ANAL INCONTINENCE
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	2	0	0	0	0	0	1
ANAL FISSURE
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
ANAL INFLAMMATION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	1 / 2 (50.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0	0
DIARRHOEA
subjects affected / exposed	12 / 31 (38.71%)	17 / 37 (45.95%)	0 / 2 (0.00%)	18 / 36 (50.00%)	4 / 8 (50.00%)	1 / 2 (50.00%)	2 / 4 (50.00%)	1 / 5 (20.00%)	2 / 4 (50.00%)	4 / 11 (36.36%)
occurrences all number	17	21	0	25	5	3	3	1	3	6
CONSTIPATION
subjects affected / exposed	8 / 31 (25.81%)	7 / 37 (18.92%)	1 / 2 (50.00%)	9 / 36 (25.00%)	1 / 8 (12.50%)	1 / 2 (50.00%)	2 / 4 (50.00%)	1 / 5 (20.00%)	3 / 4 (75.00%)	3 / 11 (27.27%)
occurrences all number	9	9	1	14	1	1	3	1	4	4
CHEILITIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
ASCITES
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	3	0	0	0	0	0	2	0	0
APHTHOUS ULCER
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
FAECALOMA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
DYSPEPSIA
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	2	0	0	0	0	1	0	0	0	1
DRY MOUTH
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
FLATULENCE
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0
FOOD POISONING
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
GASTRITIS
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	1	0	0	0	0	0	1	0	2
GASTROOESOPHAGEAL REFLUX DISEASE
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	2 / 36 (5.56%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	1	0	2	1	0	0	0	0	0
GINGIVAL BLEEDING
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	1	0	0	0	0	0	0	0	1
LOWER GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0
INTRA-ABDOMINAL HAEMORRHAGE
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
GINGIVAL HYPERTROPHY
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	0	0	0	0	0	0	1
MOUTH ULCERATION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0
OESOPHAGITIS
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0
ODYNOPHAGIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	1	0	0	1
OBSTRUCTION GASTRIC
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0
NAUSEA
subjects affected / exposed	12 / 31 (38.71%)	16 / 37 (43.24%)	1 / 2 (50.00%)	19 / 36 (52.78%)	6 / 8 (75.00%)	2 / 2 (100.00%)	3 / 4 (75.00%)	2 / 5 (40.00%)	1 / 4 (25.00%)	9 / 11 (81.82%)
occurrences all number	16	19	1	33	12	3	5	2	2	18
ORAL BLOOD BLISTER
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
ORAL DISORDER
subjects affected / exposed	3 / 31 (9.68%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	4	0	0	0	0	0	0	0	0	0
STOMATITIS
subjects affected / exposed	3 / 31 (9.68%)	3 / 37 (8.11%)	1 / 2 (50.00%)	6 / 36 (16.67%)	2 / 8 (25.00%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 11 (18.18%)
occurrences all number	3	3	1	9	5	0	2	0	0	2
ORAL DYSAESTHESIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
ORAL PAIN
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	3	0	2	0	0	0	0	0	0
PROCTALGIA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	3	0	0	0	0	0	1
PROCTITIS
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	1	1	0	0	0	0	0
TOOTH LOSS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
TOOTHACHE
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
UPPER GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0
VOMITING
subjects affected / exposed	14 / 31 (45.16%)	24 / 37 (64.86%)	1 / 2 (50.00%)	26 / 36 (72.22%)	4 / 8 (50.00%)	1 / 2 (50.00%)	4 / 4 (100.00%)	0 / 5 (0.00%)	2 / 4 (50.00%)	9 / 11 (81.82%)
occurrences all number	18	41	1	62	10	1	6	0	2	18
Hepatobiliary disorders
HEPATOMEGALY
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	1 / 2 (50.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0
HEPATIC FAILURE
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
HYPERTRANSAMINASAEMIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
HEPATIC CYTOLYSIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	1	0	0	1
Skin and subcutaneous tissue disorders
ALOPECIA
subjects affected / exposed	3 / 31 (9.68%)	1 / 37 (2.70%)	0 / 2 (0.00%)	9 / 36 (25.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	3	1	0	9	0	1	1	0	0	2
DRY SKIN
subjects affected / exposed	1 / 31 (3.23%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	0
ERYTHEMA
subjects affected / exposed	1 / 31 (3.23%)	2 / 37 (5.41%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	2	0	1	0	0	0	1	0	0
URTICARIA
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
SKIN ULCER
subjects affected / exposed	1 / 31 (3.23%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	2	0	0	0	0	0	0	0	1
SKIN HYPERPIGMENTATION
subjects affected / exposed	1 / 31 (3.23%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	1	0
RASH MACULO-PAPULAR
subjects affected / exposed	1 / 31 (3.23%)	5 / 37 (13.51%)	0 / 2 (0.00%)	3 / 36 (8.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	3 / 11 (27.27%)
occurrences all number	1	5	0	3	0	0	0	2	0	5
RASH ERYTHEMATOUS
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
PETECHIAE
subjects affected / exposed	5 / 31 (16.13%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	6	0	0	0	0	0	0	0	0	1
PRURITUS
subjects affected / exposed	3 / 31 (9.68%)	6 / 37 (16.22%)	1 / 2 (50.00%)	5 / 36 (13.89%)	1 / 8 (12.50%)	1 / 2 (50.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	4 / 11 (36.36%)
occurrences all number	5	6	2	5	1	1	0	2	0	4
PURPURA
subjects affected / exposed	2 / 31 (6.45%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0
RASH
subjects affected / exposed	3 / 31 (9.68%)	4 / 37 (10.81%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	3	4	0	1	0	0	0	0	0	0
Renal and urinary disorders
PROTEINURIA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	0	0	0	0	0	2	1
HYDRONEPHROSIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
HAEMATURIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	5 / 36 (13.89%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	5	0	0	0	0	2	0
RENAL FAILURE
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
DYSURIA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	2	0	0	2	0	0	2
CYSTITIS NONINFECTIVE
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0
GLYCOSURIA
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
URINARY RETENTION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	1	0	0	0	1	0	0
Endocrine disorders
ADRENAL INSUFFICIENCY
subjects affected / exposed	3 / 31 (9.68%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	3	0	0	0	0	0	0	0	0	0
CUSHINGOID
subjects affected / exposed	3 / 31 (9.68%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	3	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	6 / 31 (19.35%)	2 / 37 (5.41%)	0 / 2 (0.00%)	5 / 36 (13.89%)	0 / 8 (0.00%)	1 / 2 (50.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	1 / 11 (9.09%)
occurrences all number	9	2	0	5	0	2	2	1	1	1
BACK PAIN
subjects affected / exposed	6 / 31 (19.35%)	5 / 37 (13.51%)	0 / 2 (0.00%)	3 / 36 (8.33%)	1 / 8 (12.50%)	0 / 2 (0.00%)	2 / 4 (50.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	3 / 11 (27.27%)
occurrences all number	8	5	0	3	1	0	4	1	0	4
MUSCULAR WEAKNESS
subjects affected / exposed	3 / 31 (9.68%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	3	1	0	0	0	0	0	2	0	0
GROIN PAIN
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	1	0	0	0	1	1	0
FLANK PAIN
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	2	0	0	1	0	1	0
BONE PAIN
subjects affected / exposed	0 / 31 (0.00%)	4 / 37 (10.81%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	4	0	0	1	0	0	0	0	0
PAIN IN JAW
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	3 / 36 (8.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 11 (18.18%)
occurrences all number	0	1	0	4	0	0	0	0	0	2
PAIN IN EXTREMITY
subjects affected / exposed	9 / 31 (29.03%)	5 / 37 (13.51%)	0 / 2 (0.00%)	8 / 36 (22.22%)	2 / 8 (25.00%)	1 / 2 (50.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	3 / 11 (27.27%)
occurrences all number	9	9	0	10	2	1	1	1	1	4
NECK PAIN
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	0	0	0	0	1	0	1
MUSCULOSKELETAL CHEST PAIN
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	1	0	0	0	1	0	1
MUSCULOSKELETAL PAIN
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0
MYALGIA
subjects affected / exposed	5 / 31 (16.13%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	6	2	0	0	0	0	0	0	0	1
MYOSITIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
SPINAL PAIN
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	1	0	1
Infections and infestations
BLASTOCYSTIS INFECTION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
BACTEROIDES INFECTION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
ADENOVIRUS INFECTION
subjects affected / exposed	2 / 31 (6.45%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0	0	0
CANDIDA INFECTION
subjects affected / exposed	1 / 31 (3.23%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	0
ENTEROCOCCAL INFECTION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	1 / 2 (50.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0
COVID-19
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	1 / 36 (2.78%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	1	0	1	0	0	0
CORONAVIRUS INFECTION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	0	0	0	0	0	0	2
CONJUNCTIVITIS
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 11 (9.09%)
occurrences all number	1	1	0	1	0	0	0	0	1	1
CLOSTRIDIAL INFECTION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
CELLULITIS
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	2	0	0	0	1	0	0
ENTEROCOLITIS INFECTIOUS
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	1	0	1	0	0	0	0	0	1
GINGIVITIS
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
GASTROENTERITIS VIRAL
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
GASTROENTERITIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	2	1
HERPES SIMPLEX
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	1	0	2	0	0	0	0	0	0
NAIL INFECTION
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
LOWER RESPIRATORY TRACT INFECTION FUNGAL
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
LARYNGITIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
ORAL CANDIDIASIS
subjects affected / exposed	2 / 31 (6.45%)	2 / 37 (5.41%)	0 / 2 (0.00%)	2 / 36 (5.56%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	2	0	2	2	0	0	0	0	0
OTITIS MEDIA ACUTE
subjects affected / exposed	0 / 31 (0.00%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
RHINOVIRUS INFECTION
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	2	0	2	0	0	0	0	0	0
RHINITIS
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
RASH PUSTULAR
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 11 (18.18%)
occurrences all number	1	0	0	0	0	0	0	0	0	2
PNEUMONIA FUNGAL
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0
PNEUMONIA
subjects affected / exposed	2 / 31 (6.45%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	2	1	0	0	0	0	0	1	1	0
PHARYNGITIS
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0
SKIN INFECTION
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	2	0	0	0	0	0	0
URINARY TRACT INFECTION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	3 / 36 (8.33%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	5	1	0	0	1	1	0
VIRAL INFECTION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	3 / 36 (8.33%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	4	0	3	1	0	1	0	1	0
STREPTOCOCCAL INFECTION
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	1 / 2 (50.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0
STAPHYLOCOCCAL INFECTION
subjects affected / exposed	0 / 31 (0.00%)	3 / 37 (8.11%)	1 / 2 (50.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	3	1	0	1	0	0	0	0	0
Metabolism and nutrition disorders
DECREASED APPETITE
subjects affected / exposed	1 / 31 (3.23%)	8 / 37 (21.62%)	0 / 2 (0.00%)	13 / 36 (36.11%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	3 / 11 (27.27%)
occurrences all number	1	10	0	20	2	0	1	0	1	5
DEHYDRATION
subjects affected / exposed	3 / 31 (9.68%)	0 / 37 (0.00%)	0 / 2 (0.00%)	2 / 36 (5.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	3	0	0	2	0	0	0	0	0	0
FLUID RETENTION
subjects affected / exposed	0 / 31 (0.00%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
HYPERTRIGLYCERIDAEMIA
subjects affected / exposed	1 / 31 (3.23%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	0	0	0	0	0	0	2
HYPERPHOSPHATAEMIA
subjects affected / exposed	1 / 31 (3.23%)	1 / 37 (2.70%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	1	0	0	0	0	0	1	0	1
HYPERNATRAEMIA
subjects affected / exposed	1 / 31 (3.23%)	3 / 37 (8.11%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	3	0	0	0	0	0	0	0	0
HYPERMAGNESAEMIA
subjects affected / exposed	3 / 31 (9.68%)	2 / 37 (5.41%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	3	3	0	0	0	0	0	1	0	0
HYPERKALAEMIA
subjects affected / exposed	7 / 31 (22.58%)	3 / 37 (8.11%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	2 / 11 (18.18%)
occurrences all number	9	3	0	0	0	0	0	1	0	2
HYPERGLYCAEMIA
subjects affected / exposed	7 / 31 (22.58%)	4 / 37 (10.81%)	0 / 2 (0.00%)	4 / 36 (11.11%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	9	5	0	4	0	0	0	0	0	1
HYPERCALCAEMIA
subjects affected / exposed	2 / 31 (6.45%)	3 / 37 (8.11%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	4	3	0	0	0	0	0	0	0	0
HYPOALBUMINAEMIA
subjects affected / exposed	7 / 31 (22.58%)	7 / 37 (18.92%)	0 / 2 (0.00%)	8 / 36 (22.22%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	2 / 5 (40.00%)	1 / 4 (25.00%)	3 / 11 (27.27%)
occurrences all number	14	8	0	10	0	0	1	3	1	5
HYPERVOLAEMIA
subjects affected / exposed	1 / 31 (3.23%)	3 / 37 (8.11%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	4	0	1	0	0	0	0	0	1
HYPERURICAEMIA
subjects affected / exposed	3 / 31 (9.68%)	2 / 37 (5.41%)	0 / 2 (0.00%)	1 / 36 (2.78%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 11 (9.09%)
occurrences all number	3	2	0	1	0	0	0	0	0	1
HYPOCALCAEMIA
subjects affected / exposed	10 / 31 (32.26%)	5 / 37 (13.51%)	0 / 2 (0.00%)	3 / 36 (8.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	3 / 11 (27.27%)
occurrences all number	18	9	0	5	0	0	0	0	0	6
HYPOGLYCAEMIA
subjects affected / exposed	4 / 31 (12.90%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 11 (0.00%)
occurrences all number	6	0	0	0	0	0	0	0	0	0
HYPOKALAEMIA
subjects affected / exposed	16 / 31 (51.61%)	17 / 37 (45.95%)	0 / 2 (0.00%)	11 / 36 (30.56%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	2 / 4 (50.00%)	5 / 11 (45.45%)
occurrences all number	32	28	0	13	0	0	1	1	4	10
HYPOMAGNESAEMIA
subjects affected / exposed	6 / 31 (19.35%)	5 / 37 (13.51%)	0 / 2 (0.00%)	0 / 36 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	3 / 11 (27.27%)
occurrences all number	12	11	0	0	1	0	0	0	1	3
HYPONATRAEMIA
subjects affected / exposed	9 / 31 (29.03%)	6 / 37 (16.22%)	0 / 2 (0.00%)	3 / 36 (8.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	3 / 5 (60.00%)	1 / 4 (25.00%)	4 / 11 (36.36%)
occurrences all number	13	8	0	6	0	0	0	3	3	4
REFEEDING SYNDROME
subjects affected / exposed	0 / 31 (0.00%)	0 / 37 (0.00%)	0 / 2 (0.00%)	0 / 36 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
HYPOPHOSPHATAEMIA
subjects affected / exposed	13 / 31 (41.94%)	7 / 37 (18.92%)	0 / 2 (0.00%)	6 / 36 (16.67%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	1 / 4 (25.00%)	4 / 11 (36.36%)
occurrences all number	23	8	0	10	0	0	0	2	3	7

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Were there any global substantial amendments to the protocol? Yes

13 Oct 2017

Amendment 1 -Clarified that subjects in Part 1 with relapsed/refractory malignancies must not have available curative treatment options to be eligible for study -Updated Part 1 Dose Escalation Guidelines to specify that a minimum of 3 subjects will have bone marrow involvement and a minimum of 3 subjects will not have bone marrow involvement -Clarified participation of Germany in Part 2 only -Updated contraception recommendations to include addition of a barrier method for women using hormonal contraceptives -Clarified that tumor assessments will be performed according to the specified criteria for each tumor type -Specified that blood samples are mandatory if part of routine blood draw -Defined a low-fat meal and provided a formula for calculation -Added that cerebrospinal fluid analysis is exploratory -Clarified that plasma concentration or CSF concentration of possible venetoclax metabolites may be determined using validated or non-validated methods -Specified assessments for subjects who are deriving clinical benefit and stay on venetoclax therapy beyond the 9 month duration -Noted that subjects with TCF3-HLF ALL require distinct chemotherapy regimens than those already listed in the protocol -Updated and clarified adverse event reporting and documentation process -Updated Dose-Limiting Toxicity (DLT) criteria -Defined efficacy endpoints that will be assessed -Clarified that diagnosis of TCF3-HLF positive ALL should be confirmed prior to study entry -Specified MRD assessments for subjects with TCF3-HLF positive ALL -Included dosing information for venetoclax target doses for use in combination with certain chemotherapies or if target dose is de-escalated or escalated in Part 1 (Appendix M) and target doses when co-administered with moderate and strong CYP3A inhibitors (Appendix N) -Updated Appendix R with new International Neuroblastoma Response Criteria

23 Feb 2018

Amendment 2 -Updated the number of subjects enrolled in the study -Updated the timing of study drug administration to allow flexibility for dosing -Clarified that subjects with confirmed TCF3-HLF ALL and BCL-2 expression will enroll in the fifth cohort -Clarified the criteria to begin the second stage of enrollment into individual cohorts -Clarified CNS disease is to be confirmed by lumbar puncture in order to obtain results from CSF sample collection -Updated Section 5.2.1 Part 1 (Dose Determination) to specify the minimum number of subjects in each age group: < 2, 2 –11, and 12 –17 years of age -Clarified in Part 2 (cohort expansion portion) that archived scans within 42 days of enrollment are allowed -Noted that subjects should not receive a live vaccine before (4 weeks before) or during treatment, unless in discussion with the AbbVie TA MD -Clarified the procedure must be followed for uric acid samples containing rasburicase only -Clarified subjects that have completed the DLT period in Part 1 following discussion with AbbVie TA MD may switch to oral tablets, to add rinse step instruction for 800 mg dose preparation, and to clarify that patients must take all of the solution and rinses within 60 minutes of preparation -Clarified venetoclax dose should be withheld if persistent blood chemistry change suggestive of TLS is reported -Included additional DLT criteria stating Grade 4 neutropenia or thrombocytopenia lasting ≥42 days from the start of venetoclax in the absence of evidence of active leukemia -Added diltiazem and removed azithromycin based on recent data that supports inclusion and exclusion respectively

19 Oct 2018

Amendment 3 -Increased the number of subjects to be enrolled to 165 -Added a 400 mg and 600 mg adult-equivalent target dose of venetoclax tablet for those with solid tumors -Incorporated the addition of the Dose Escalation/De-escalation for solid tumors in Part 1 -Provided guidance on how to manage Grade 3 and 4 neutropenia and thrombocytopenia in solid tumor subjects -Added Section 5.1.2.1 Part 1 –Dose Escalation/De-escalation in Neuroblastoma and Solid Tumor Patients (Cohorts S1, S2, S_ 1, S_ 2) to include a Dose Escalation/De-escalation for solid tumor subjects in Part 1 -Clarified required time points for clinical laboratory tests -Updated venetoclax dosing to allow for combination therapy earlier for relapsed and/or refractory tumors in pediatric patients -Updated rinse volumes for certain doses were updated and/or the second rinse was removed based on newly generated analytic data supporting the change -Revised dosing instructions for venetoclax tablets for oral suspension and added instructions for venetoclax oral tablets -Increased dose of chemotherapy from a palliative dose to a standard dose tolerated by pediatric subjects -Allowed a one-time switch of the chemotherapy regimen for AML and ALL subjects -Updated Appendix H Pharmacokinetic Sampling for Subjects with ALL, AML, or NHL in Part 2 (Cohort Expansion) to add Day 8 Intensive PK sampling -Updated Appendix I Pharmacokinetic Sampling For Subjects with Solid Tumors (Excluding NHL) -Updated Appendix M Age and Weight Adjusted Adult-Equivalent Venetoclax dose and Appendix N Adult Equivalent Venetoclax Doses When Moderate and Strong CYP3A Inhibitors are Administered Concomitantly

25 Jun 2019

Amendment 4 -Added myeloid growth factor to the treatment options to minimize neutropenia and thrombocytopenia; Table 5 was revised to provide further guidance on the dose and duration of venetoclax and chemotherapy following hematologic toxicity -Updated Inclusion Criteria to add hepatic function criteria for subjects who previously received inotuzumab ozogamicin within 30 days of the first dose of study drug -Modified Exclusion Criteria number 2 to only exclude subjects with CNS disease with cranial involvement requiring radiation; Criteria number 3 was changed to exclude subjects who were treated with inotuzumab ozogamicin within 30 days of the first dose of study drug and to add exception for Ph+ ALL patients receiving TKI anti-cancer therapies -Updated Section 5.2.4 Contraceptive Recommendations to add surgical sterilization for females and vasectomy for males as acceptable contraceptive methods -Updated Sections 6.1.3 Relationship to Study Drug and Section 6.1.4 Adverse Event Collection Period -Updated Section 6.1.8 Toxicity Management for Dose Limiting Toxicities to update the DLT criteria for patients with NHL, neuroblastoma, and other solid tumors -Updated Appendix H Pharmacokinetic Sampling for Subjects with ALL, AML, or NHL to clarify the pharmacokinetic sampling requirements for neonates -Updated Appendix N Table. Adult-Equivalent Venetoclax Doses (mg) When Moderate and Strong CYP3A Inhibitors are Administered Concomitantly, to correct the dose for subjects with hematologic malignancies using the 800 mg adult equivalent dose weighing ≥45 kg on day 1 of the dose ramp up, from 25 mg to 30 mg -Updated Section 5.5.2 Chemotherapy Administered to include subjects who experience an acute lineage switch while on study or present with mixed lineage leukemia prior to enrollment the option to be treated using chemotherapy options for either AML or ALL

09 Mar 2021

Amendment 5 -Revised TLS prophylaxis requirements for subjects with solid tumors -Increased number of subjects projected to enroll from 30 to 45 -Clarified that in Part 2, neuroblastoma and solid tumor subjects are not required to recover neutrophil and platelet counts to start the next cycle of combination therapy -Clarified that agents that increase platelet production may be administered -Provided flexibility for subjects on the intermittent dosing schedule -Added gemtuzumab ozogamicin to inclusion criteria number 3 -Clarified that subjects with TCF3-HLF-ALL in the fifth cohort are not required to have evidence of BCL-2 expression -Allowed for collection of labs prior to consent; clarified review of the Day 1 pre-dose labs when Day –1 labs are found to be clinically acceptable; replaced wording of "liquid tumor" with hematologic malignancies/NHL; revised TLS lab collection timepoints for subjects with solid tumors; clarified labs collected at unscheduled timepoints should be entered into EDC as unscheduled visits -Clarified that in Part 2, neuroblastoma and solid tumor subjects are not required to recover neutrophil and platelet counts to start the next cycle of combination therapy -Updated Appendix D to include other hematologic malignancy patients -Provided guidance on the intermittent dosing schedule regarding labs, scans, venetoclax administration and bone marrow aspirate and/or biopsy; clarified a bone marrow biopsy and/or aspirate is required for subjects with relevant tumor types -Added other hematologic malignancy subjects and clarified W2 Day 8 collection for neonates -Updated Pharmacokinetic Sampling to add cohorts S1 and S2 and remove Part 2 cohort expansion -Incorporated necessary protocol modifications due to the COVID-19 pandemic -Added information that remote monitoring may be employed as needed

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase 1 Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients with Relapsed or Refractory Malignancies

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With Adverse Events

Primary: Number of Participants With Adverse Events

Primary: Part 1: Number of Participants With Dose Limiting Toxicities (DLT) of Venetoclax Monotherapy

Primary: Part 1: Number of Participants With Dose Limiting Toxicities (DLT) of Venetoclax Monotherapy

Primary: Part 1: Maximum Observed Plasma Concentration (Cmax) of Venetoclax (Week 2, Day 8) of Venetoclax (Week 2, Day 8)

Primary: Part 1: Maximum Observed Plasma Concentration (Cmax) of Venetoclax (Week 2, Day 8) of Venetoclax (Week 2, Day 8)

Primary: Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax (Week 2, Day 8)

Primary: Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax (Week 2, Day 8)

Primary: Part 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to 24 Hours (AUC0-24) of Venetoclax (Week 2, Day 8)

Primary: Part 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to 24 Hours (AUC0-24) of Venetoclax (Week 2, Day 8)

Primary: Part 1: Apparent clearance (CL/F) of venetoclax (Week 2, Day 8)

Primary: Part 1: Apparent clearance (CL/F) of venetoclax (Week 2, Day 8)

Secondary: Objective Response Rate

Secondary: Objective Response Rate

Secondary: Complete Response (CR) Rate

Secondary: Complete Response (CR) Rate

Secondary: Partial Response Rate

Secondary: Partial Response Rate

Secondary: Progression-free Survival (PFS)

Secondary: Progression-free Survival (PFS)

Secondary: Overall Survival

Secondary: Overall Survival

Secondary: Minimal Residual Disease (MRD) negativity rate

Secondary: Minimal Residual Disease (MRD) negativity rate

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 1 Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients with Relapsed or Refractory Malignancies