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Clinical Trial Results:
A Multicenter Phase 2 Study to Evaluate Subcutaneous Daratumumab in Combination with Standard Multiple Myeloma Treatment Regimens

Summary
EudraCT number	2017-004203-41
Trial protocol	GB DE CZ ES
Global end of trial date	07 Dec 2020

Results information
Results version number	v1(current)
This version publication date	24 Nov 2023
First version publication date	24 Nov 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

54767414MMY2040

ISRCTN number

US NCT number

NCT03412565

WHO universal trial number (UTN)

Sponsor organisation name

Janssen-Cilag International NV

Sponsor organisation address

Turnhoutseweg 30, Beerse, Belgium, 2340

Public contact

Clinical Registry Group, Janssen-Cilag International NV, ClinicalTrialsEU@its.jnj.com

Scientific contact

Clinical Registry Group, Janssen-Cilag International NV, ClinicalTrialsEU@its.jnj.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

07 Dec 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

07 Dec 2020

Was the trial ended prematurely?

Main objective of the trial

The main objective of this trial was to evaluate the clinical benefit of subcutaneous (SC) daratumumab administered in combination with standard multiple myeloma (MM) regimens in subjects with MM as measured by overall response rate (ORR) or very good partial response (VGPR) or better rate.

Protection of trial subjects

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

02 May 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Brazil: 5

Country: Number of subjects enrolled

Czechia: 23

Country: Number of subjects enrolled

Germany: 19

Country: Number of subjects enrolled

Spain: 55

Country: Number of subjects enrolled

United Kingdom: 29

Country: Number of subjects enrolled

France: 79

Country: Number of subjects enrolled

Israel: 21

Country: Number of subjects enrolled

Japan: 4

Country: Number of subjects enrolled

United States: 30

Worldwide total number of subjects

265

EEA total number of subjects

176

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)

115

From 65 to 84 years

149

85 years and over

Subject disposition

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Recruitment details

Screening details

Out of 265 enrolled subjects, 114 subjects completed the study.

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

Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)

Arm description

Subjects received daratumumab 1800 milligrams (mg) as a subcutaneous (SC) injection on Days 1, 8 and 15 of Cycles 1 to 3 (each cycle of 21 days) and on Day 1 of Cycle 4; bortezomib 1.3 milligrams per square meter (mg/m^2) SC injection on Days 1, 4, 8 and 11 of Cycles 1 to 4; lenalidomide 25 mg orally on Day 1 through Day 14 of Cycles 1 to 4 and dexamethasone 20 mg orally or intravenously (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4.

Arm type

Experimental

Investigational medicinal product name

Daratumumab

Investigational medicinal product code

Other name

JNJ-54767414

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subject received daratumumab 1800 mg as a SC injection on Days 1, 8 and 15 of Cycles 1 to 3 (each cycle of 21 days) and on Day 1 of Cycle 4.

Investigational medicinal product name

Bortezomib

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received bortezomib 1.3 mg/m^2 SC injection on Days 1, 4, 8 and 11 of Cycles 1 to 4.

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Subjects received lenalidomide 25 mg orally on Day 1 through Day 14 of Cycles 1 to 4.

Investigational medicinal product name

Dexamethasone

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet, Infusion

Routes of administration

Intravenous use, Oral use

Dosage and administration details

Subjects received dexamethasone 20 mg either orally or IV on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4.

D + Bortezomib + Melphalan + Prednisone (D-VMP)

Arm description

Subjects received daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1, then on Days 1 and 22 in Cycles 2 to 9, and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; bortezomib 1.3 mg/m^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m^2 orally on Days 1 to 4 of cycles 1 to 9.

Arm type

Experimental

Investigational medicinal product name

Daratumumab

Investigational medicinal product code

Other name

JNJ-54767414

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Investigational medicinal product name

Bortezomib

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received bortezomib 1.3 mg/m^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9.

Investigational medicinal product name

Melphalan

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received melphalan 9 mg/m^2 orally on Day 1 through Day 4 of Cycles 1 to 9.

Investigational medicinal product name

Prednisone

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received prednisone 60 mg/m^2 orally on Days 1 to 4 of cycles 1 to 9.

Daratumumab + Lenalidomide + Dexamethasone (D-Rd)

Arm description

Subjects received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2, then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.

Arm type

Experimental

Investigational medicinal product name

Daratumumab

Investigational medicinal product code

Other name

JNJ-54767414

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Investigational medicinal product name

Dexamethasone

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet, Infusion

Routes of administration

Oral use, Intravenous use

Dosage and administration details

Subjects received dexamethasone 40 mg either orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Subjects received lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study.

Daratumumab + Carfilzomib + Dexamethasone (D-Kd)

Arm description

Subjects received daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days), then on Day 1 and 15 of Cycles 3 to 6, and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months; Carfilzomib 20 mg/m^2 IV on Day 1 of Cycle 1 only, then 70 mg/m^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.

Arm type

Experimental

Investigational medicinal product name

Daratumumab

Investigational medicinal product code

Other name

JNJ-54767414

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Investigational medicinal product name

Dexamethasone

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet, Infusion

Routes of administration

Oral use, Intravenous use

Dosage and administration details

Subjects received dexamethasone 40 mg either orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months.

Investigational medicinal product name

Carfilzomib

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received Carfilzomib 20 mg/m^2 IV on Day 1 of Cycle 1 only, then 70 mg/m^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 7 months

Number of subjects in period 1	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Started	67	67	65	66
Completed	66	19	14	15
Not completed	1	48	51	51
Consent withdrawn by subject	-	4	5	5
Physician decision	-	-	-	1
Data collection ended	-	41	41	40
Death	1	3	4	5
Lost to follow-up	-	-	1	-

Baseline characteristics

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Reporting group title

Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)

Reporting group description

Reporting group title

D + Bortezomib + Melphalan + Prednisone (D-VMP)

Reporting group description

Reporting group title

Daratumumab + Lenalidomide + Dexamethasone (D-Rd)

Reporting group description

Reporting group title

Daratumumab + Carfilzomib + Dexamethasone (D-Kd)

Reporting group description

Reporting group values	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)	Total
Number of subjects	67	67	65	66	265
Title for AgeCategorical
Units: subjects
Children (2-11 years)	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0
Adults (18-64 years)	54	0	22	39	115
From 65 to 84 years	13	66	43	27	149
85 years and over	0	1	0	0	1
Title for AgeContinuous
Units: years
arithmetic mean (standard deviation)	57.3 ( 9.47 )	74.9 ( 4.54 )	66.8 ( 9.58 )	61 ( 9.77 )	-
Title for Gender
Units: subjects
Female	19	36	20	32	107
Male	48	31	45	34	158

End points

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Reporting group title

Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)

Reporting group description

Reporting group title

D + Bortezomib + Melphalan + Prednisone (D-VMP)

Reporting group description

Reporting group title

Daratumumab + Lenalidomide + Dexamethasone (D-Rd)

Reporting group description

Reporting group title

Daratumumab + Carfilzomib + Dexamethasone (D-Kd)

Reporting group description

Primary: D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)

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End point title

D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR) ^[1] ^[2]

End point description

ORR was defined as percentage of subjects who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to less than (<) 200 milligrams (mg) per 24 hours, If serum and urine M-protein are not measurable, a decrease of >=50% in difference between involved and uninvolved free light chain (FLC) levels is required in place of M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30. All treated analysis set included all subjects who received at least 1 dose of study treatment. This primary endpoint was planned to be analysed for D-VMP, D-Rd and D-Kd cohorts only.

End point type

Primary

End point timeframe

Up to 2 years 3 months

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be reported for this endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be reported for specified arms only.

End point values	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Number of subjects analysed	67	65	66
Units: percentage of subjects
number (confidence interval 90%)	88.1 (79.5 to 93.9)	90.8 (82.6 to 95.9)	84.8 (75.7 to 91.5)

No statistical analyses for this end point

Primary: D-VRd Cohort: Percentage of Subjects With Very Good Partial Response (VGPR) or Better Response

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End point title

D-VRd Cohort: Percentage of Subjects With Very Good Partial Response (VGPR) or Better Response ^[3] ^[4]

End point description

VGPR or better rate was defined as the percentage of subjects who achieved VGPR or complete response (CR) (including stringent complete response [sCR]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level <100 mg/24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry. All treated analysis set included all subjects who received at least 1 dose of study treatment. This primary endpoint was planned to be analysed for D-VRd cohort only.

End point type

Primary

End point timeframe

Up to 2 years and 3 months

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be reported for this endpoint.
[4] - 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: This endpoint was planned to be reported for specified arms only.

End point values	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)
Number of subjects analysed	67
Units: percentage of subjects
number (confidence interval 90%)	71.6 (61.2 to 80.6)

No statistical analyses for this end point

Secondary: Maximum Observed Serum Concentration (Cmax) of Daratumumab

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End point title

Maximum Observed Serum Concentration (Cmax) of Daratumumab

End point description

Cmax was defined as maximum serum concentration observed following daratumumab administration. Each cycle for: D-VRd cohort is of 21 days, D-VMP cohort is of 42 days and D-Rd and D-Kd cohorts is of 28 days. Each cohort have a treatment period of 84 days. Pharmacokinetics (PK) analysis set: subjects who received at least 1 dose of daratumumab SC and had at least 1 PK sample value after first dose. 'N' (number of subjects analysed): subjects evaluated for this endpoint; 'n' (number analysed): subjects analysed at specific timepoints. The “0” in the number analysed field indicates that no subject was evaluable for PK at that timepoint. Here, '99999' indicates that no subject was available for analysis.

End point type

Secondary

End point timeframe

D-VRd: Day 4 of Cycles 1 and 4 and post treatment at Week 8; D-VMP: Day 4 of Cycles 1 and 2 and post treatment at Week 8; D-Rd and D-Kd: Day 4 of Cycles 1 and 3 and post treatment at Week 8

End point values	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Number of subjects analysed	60	66	56	57
Units: micrograms per milliliter (mcg/mL)
arithmetic mean (standard deviation)
Cycle 1 Day 4 (n=60, 66, 56, 57)	100 ( 48.5 )	98.6 ( 51.6 )	108 ( 49.9 )	137 ( 56.7 )
Cycle 2 Day 4 (n=0, 55, 0, 0)	99999 ( 99999 )	612 ( 256 )	99999 ( 99999 )	99999 ( 99999 )
Cycle 3 Day 4 (n= 0, 0, 50, 45)	99999 ( 99999 )	99999 ( 99999 )	648 ( 238 )	869 ( 274 )
Cycle 4 Day 4 (n= 56, 0, 0, 0)	746 ( 275 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )
Post-treatment Phase Week 8 (n=43, 1, 0, 6)	263 ( 190 )	162 ( 99999 )	99999 ( 99999 )	49.3 ( 106 )

No statistical analyses for this end point

Secondary: D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Subjects With VGPR or Better Response

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End point title

D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Subjects With VGPR or Better Response ^[5]

End point description

VGPR or better rate was defined as the percentage of subjects who achieved VGPR or CR (including sCR) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry. All treated analysis set included all subjects who received at least 1 dose of study treatment. This secondary endpoint was planned to be analysed for D-VMP, D-Rd and D-Kd cohorts only.

End point type

Secondary

End point timeframe

From baseline up to 2 years 7 months

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was planned to be reported for specified arms only.

End point values	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Number of subjects analysed	67	65	66
Units: percentage of subjects
number (confidence interval 90%)	77.6 (67.6 to 85.7)	80.0 (70.1 to 87.7)	77.3 (67.2 to 85.4)

No statistical analyses for this end point

Secondary: Percentage of Subjects with Infusion-Related Reactions (IRRs)

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End point title

Percentage of Subjects with Infusion-Related Reactions (IRRs)

End point description

Percentage of subjects with IRRs were reported. The administration-related systemic reactions are referred to as IRRs. All treated analysis set included all subjects who received at least 1 dose of study treatment.

End point type

Secondary

End point timeframe

For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months

End point values	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Number of subjects analysed	67	67	65	66
Units: percentage of subjects
number (confidence interval 90%)	9.0 (4.0 to 16.9)	9.0 (4.0 to 16.9)	4.6 (1.3 to 11.5)	4.5 (1.3 to 11.3)

No statistical analyses for this end point

Secondary: D-VRd Cohort: Overall Response Rate (ORR)

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End point title

D-VRd Cohort: Overall Response Rate (ORR) ^[6]

End point description

ORR was defined as the percentage of subjects who achieved a PR or better, IMWG criteria, during the study or during follow up. IMWG criteria for PR >= 50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% or to <200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required. All treated analysis set included all subjects who received at least 1 dose of study treatment. This secondary endpoint was planned to be analysed for D-VRd cohort only.

End point type

Secondary

End point timeframe

Up to 2 years and 3 months

Notes
[6] - 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: This endpoint was planned to be reported for specified arms only.

End point values	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)
Number of subjects analysed	67
Units: percentage of subjects
number (confidence interval 90%)	97.0 (90.9 to 99.5)

No statistical analyses for this end point

Secondary: Percentage of Subjects With CR or Better Response

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End point title

Percentage of Subjects With CR or Better Response

End point description

CR or better rate was defined as the percentage of subjects with a CR or better response (that is, CR and sCR) as per IMWG criteria. CR: as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (<) 5 percent plasma cells in bone marrow; sCR: CR plus normal FLC ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. All treated analysis set included all subjects who received at least 1 dose of study treatment.

End point type

Secondary

End point timeframe

For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months

End point values	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Number of subjects analysed	67	67	65	66
Units: percentage of subjects
number (confidence interval 90%)	16.4 (9.5 to 25.7)	55.2 (44.5 to 65.6)	50.8 (39.9 to 61.5)	42.4 (32.1 to 53.3)

No statistical analyses for this end point

Secondary: D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)

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End point title

D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR) ^[7]

End point description

DOR=time from date of initial documented response (PR or better response) to date of first documented evidence of progressive disease (PD) or death due to PD. PD=increase of 25% from lowest response value in one of following: serum and urine M-component (absolute increase must be >=0.5 gram per deciliter [g/dL] and >=200 mg/24 hours); only in subjects without measurable serum and urine M-protein level difference between involved and uninvolved FLC level (absolute increase must be >10 mg/dL);definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 mg/dL). Analysis population included number of responders (partial response or better) in each cohort. Here, ‘99999’ indicates that median duration of response was not estimable due to less number of events.

End point type

Secondary

End point timeframe

From baseline up to 2 years 7 months

Notes
[7] - 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: This endpoint was planned to be reported for specified arms only.

End point values	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Number of subjects analysed	60	61	56
Units: months
median (full range (min-max))	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: Percentage of Subjects with Anti-Daratumumab Antibodies

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End point title

Percentage of Subjects with Anti-Daratumumab Antibodies

End point description

Percentage of subjects with antibodies to daratumumab were reported. Immunogenicity-evaluable analysis set was defined as all subjects who received at least 1 dose administration of daratumumab SC and had at least 1 immunogenicity sample for detection of anti-daratumumab antibodies after the first dose.

End point type

Secondary

End point timeframe

For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months

End point values	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Number of subjects analysed	65	64	62	64
Units: percentage of subjects
number (not applicable)	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects with Anti-rHuPH20 Antibodies

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End point title

Percentage of Subjects with Anti-rHuPH20 Antibodies

End point description

Percentage of subjects with antibodies to rHuPH20 were reported. Immunogenicity-evaluable analysis set for rHuPH20 is defined as all subjects who received at least one dose of daratumumab SC and had appropriate plasma samples for detection of antibodies to rHuPH20 (at least 1 sample after the start of the first dose of daratumumab SC).

End point type

Secondary

End point timeframe

For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months

End point values	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Number of subjects analysed	66	64	62	64
Units: percentage of subjects
number (not applicable)	6.1	3.1	4.8	4.7

No statistical analyses for this end point

Secondary: D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Subjects with Minimal Residual Disease (MRD) Negative Rate

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End point title

D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Subjects with Minimal Residual Disease (MRD) Negative Rate ^[8]

End point description

MRD negativity rate was defined as the percentage of subjects who were considered MRD negative after MRD testing at any timepoint after the first dose by bone marrow aspirate. MRD negativity rate was assessed by next-generation sequencing at a threshold of <10^5. All treated analysis set included all subjects who have received at least 1 dose of study treatment. This secondary endpoint was planned to be analysed for D-VMP, D-Rd and D-Kd cohorts only.

End point type

Secondary

End point timeframe

Up to 2 years and 3 months

Notes
[8] - 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: This endpoint was planned to be reported for specified arms only.

End point values	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Number of subjects analysed	67	65	66
Units: percentage of subjects
number (confidence interval 90%)	25.4 (16.9 to 35.6)	21.5 (13.5 to 31.6)	27.3 (18.4 to 37.7)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From baseline up to 2 years 7 months

Adverse event reporting additional description

All treated analysis set included all subjects who had received at least 1 dose of study treatment.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

21.1/23.1

Reporting group title

Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)

Reporting group description

Reporting group title

D + Bortezomib + Melphalan + Prednisone (D-VMP)

Reporting group description

Reporting group title

Daratumumab + Lenalidomide + Dexamethasone (D-Rd)

Reporting group description

Reporting group title

Daratumumab + Carfilzomib + Dexamethasone (D-Kd)

Reporting group description

Serious adverse events	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Total subjects affected by serious adverse events
subjects affected / exposed	19 / 67 (28.36%)	30 / 67 (44.78%)	37 / 65 (56.92%)	22 / 66 (33.33%)
number of deaths (all causes)	1	3	4	5
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous Cell Carcinoma of Skin
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Plasma Cell Myeloma
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myelodysplastic Syndrome
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Adenocarcinoma Pancreas
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute Myeloid Leukaemia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic Neoplasm
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep Vein Thrombosis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	1 / 67 (1.49%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Cardiac Ablation
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Performance Status Decreased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Non-Cardiac Chest Pain
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General Physical Health Deterioration
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	2 / 67 (2.99%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chills
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	4 / 67 (5.97%)	5 / 67 (7.46%)	3 / 65 (4.62%)	2 / 66 (3.03%)
occurrences causally related to treatment / all	4 / 5	3 / 5	0 / 3	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Uterine Prolapse
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
subjects affected / exposed	2 / 67 (2.99%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 1	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic Obstructive Pulmonary Disease
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute Respiratory Failure
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Failure
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Pulmonary Hypertension
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Body Temperature Increased
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oxygen Saturation Decreased
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respirovirus Test Positive
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Transaminases Increased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hip Fracture
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Limb Injury
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thoracic Vertebral Fracture
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wrist Fracture
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Arrhythmia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Left Ventricular Dysfunction
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial Infarction
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Cardiac Failure Congestive
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Atrial Fibrillation
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial Flutter
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac Failure
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	3 / 65 (4.62%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Nervous system disorders
Cerebellar Haematoma
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Incoherent
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Generalised Tonic-Clonic Seizure
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral Small Vessel Ischaemic Disease
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic Stroke
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal Cord Compression
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Loss of Consciousness
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thalamic Infarction
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vith Nerve Paresis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	3 / 65 (4.62%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anaemia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Febrile Neutropenia
subjects affected / exposed	1 / 67 (1.49%)	2 / 67 (2.99%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	2 / 3	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	1 / 67 (1.49%)	2 / 67 (2.99%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 2	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Ophthalmic Vein Thrombosis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	5 / 65 (7.69%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	2 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	2 / 67 (2.99%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal Haemorrhage
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Skin Lesion
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rash Maculo-Papular
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rash Pruritic
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperhidrosis
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal Impairment
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal Failure
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute Kidney Injury
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	3 / 65 (4.62%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Muscular Weakness
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypercreatinaemia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bone Pain
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Back Pain
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arthralgia
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal Chest Pain
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal Pain
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Campylobacter Gastroenteritis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infection
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia Urinary Tract Infection
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enterobacter Infection
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea Infectious
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Covid-19 Pneumonia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Covid-19
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium Difficile Colitis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infective Exacerbation of Chronic Obstructive Airways Disease
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper Respiratory Tract Infection
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	3 / 65 (4.62%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Pneumonia
subjects affected / exposed	1 / 67 (1.49%)	6 / 67 (8.96%)	9 / 65 (13.85%)	3 / 66 (4.55%)
occurrences causally related to treatment / all	1 / 1	1 / 7	4 / 10	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumocystis Jirovecii Pneumonia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary Tract Infection
subjects affected / exposed	1 / 67 (1.49%)	2 / 67 (2.99%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenic Sepsis
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	3 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
Lower Respiratory Tract Infection
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	3 / 65 (4.62%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	4 / 65 (6.15%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 1	2 / 4	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumococcal Sepsis
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral Pharyngitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyperkalaemia
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic Metabolic Decompensation
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)	D + Bortezomib + Melphalan + Prednisone (D-VMP)	Daratumumab + Lenalidomide + Dexamethasone (D-Rd)	Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Total subjects affected by non serious adverse events
subjects affected / exposed	67 / 67 (100.00%)	67 / 67 (100.00%)	65 / 65 (100.00%)	66 / 66 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin Papilloma
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Seborrhoeic Keratosis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Pituitary Tumour Benign
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Malignant Melanoma
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Lipoma
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Gastrointestinal Tract Adenoma
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Colon Adenoma
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Basal Cell Carcinoma
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Tumour Pain
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Vascular disorders
Aortic Stenosis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Venous Thrombosis Limb
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	0	1	1
Deep Vein Thrombosis
subjects affected / exposed	3 / 67 (4.48%)	1 / 67 (1.49%)	4 / 65 (6.15%)	2 / 66 (3.03%)
occurrences all number	3	1	4	2
Flushing
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	1	0	0	1
Haematoma
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	2 / 66 (3.03%)
occurrences all number	0	0	1	2
Hot Flush
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Hypertension
subjects affected / exposed	1 / 67 (1.49%)	10 / 67 (14.93%)	8 / 65 (12.31%)	23 / 66 (34.85%)
occurrences all number	1	19	9	55
Hypotension
subjects affected / exposed	3 / 67 (4.48%)	8 / 67 (11.94%)	4 / 65 (6.15%)	2 / 66 (3.03%)
occurrences all number	3	8	5	2
Orthostatic Hypotension
subjects affected / exposed	1 / 67 (1.49%)	3 / 67 (4.48%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	3	0	0
Peripheral Coldness
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Phlebitis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	2 / 66 (3.03%)
occurrences all number	0	0	1	2
Thrombophlebitis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	3 / 66 (4.55%)
occurrences all number	0	0	0	3
Thrombophlebitis Superficial
subjects affected / exposed	2 / 67 (2.99%)	0 / 67 (0.00%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	2	0	0	2
Thrombosed Varicose Vein
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Varicose Vein
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Vascular Pain
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Cyanosis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
White Coat Hypertension
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	18 / 67 (26.87%)	10 / 67 (14.93%)	19 / 65 (29.23%)	13 / 66 (19.70%)
occurrences all number	25	20	36	16
Administration Site Erythema
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	2
Administration Site Pruritus
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Administration Site Swelling
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Asthenia
subjects affected / exposed	10 / 67 (14.93%)	17 / 67 (25.37%)	21 / 65 (32.31%)	14 / 66 (21.21%)
occurrences all number	12	31	38	18
Catheter Site Erythema
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Chest Discomfort
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	1	1	0	1
Chest Pain
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	3 / 65 (4.62%)	1 / 66 (1.52%)
occurrences all number	0	0	3	1
Chills
subjects affected / exposed	8 / 67 (11.94%)	3 / 67 (4.48%)	4 / 65 (6.15%)	2 / 66 (3.03%)
occurrences all number	10	3	5	2
Cyst
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Discomfort
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Face Oedema
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	3 / 66 (4.55%)
occurrences all number	0	0	1	7
Facial Pain
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Feeling Cold
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	2	0	0
Injection Site Rash
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	1	0	0
Generalised Oedema
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	3
Hernia Pain
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Hyperthermia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Hypothermia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	1	0	1
Impaired Healing
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Inflammation
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Influenza Like Illness
subjects affected / exposed	0 / 67 (0.00%)	3 / 67 (4.48%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	3	2	0
Infusion Site Pain
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Injection Site Bruising
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Injection Site Eczema
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Injection Site Erythema
subjects affected / exposed	9 / 67 (13.43%)	5 / 67 (7.46%)	0 / 65 (0.00%)	5 / 66 (7.58%)
occurrences all number	12	13	0	5
Injection Site Haemorrhage
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Injection Site Induration
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Injection Site Pain
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	0	0	0	4
Injection Site Pruritus
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	3	0	0
General Physical Health Deterioration
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	1	0	0
Localised Oedema
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	0	0	0	3
Injection Site Swelling
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Vaccination Site Erythema
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Temperature Regulation Disorder
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Swelling Face
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Swelling
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	0	0	0	2
Secretion Discharge
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Pyrexia
subjects affected / exposed	22 / 67 (32.84%)	22 / 67 (32.84%)	16 / 65 (24.62%)	14 / 66 (21.21%)
occurrences all number	30	32	23	22
Peripheral Swelling
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	3 / 66 (4.55%)
occurrences all number	0	1	0	3
Pain
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	3 / 65 (4.62%)	2 / 66 (3.03%)
occurrences all number	0	0	3	2
Oedema Peripheral
subjects affected / exposed	13 / 67 (19.40%)	11 / 67 (16.42%)	15 / 65 (23.08%)	12 / 66 (18.18%)
occurrences all number	14	16	30	23
Oedema
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	2	0	0
Injection Site Reaction
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Malaise
subjects affected / exposed	0 / 67 (0.00%)	5 / 67 (7.46%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	9	1	0
Mucosal Inflammation
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	1	1	0
Multiple Organ Dysfunction Syndrome
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Non-Cardiac Chest Pain
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	3 / 65 (4.62%)	0 / 66 (0.00%)
occurrences all number	1	1	3	0
Immune system disorders
Drug Hypersensitivity
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Allergy to Plants
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Hypogammaglobulinaemia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	2 / 66 (3.03%)
occurrences all number	0	1	1	2
Reproductive system and breast disorders
Benign Prostatic Hyperplasia
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	2	0	0	1
Breast Haematoma
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Cystocele
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Genital Rash
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Pelvic Discomfort
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	2
Pelvic Floor Muscle Weakness
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Pelvic Pain
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Scrotal Erythema
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Uterine Prolapse
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	1	0	1
Vaginal Haemorrhage
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Vulvovaginal Pruritus
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Atelectasis
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Bronchopneumopathy
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Cough
subjects affected / exposed	5 / 67 (7.46%)	12 / 67 (17.91%)	10 / 65 (15.38%)	13 / 66 (19.70%)
occurrences all number	5	13	11	13
Dysphonia
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	5 / 65 (7.69%)	0 / 66 (0.00%)
occurrences all number	0	2	5	0
Dyspnoea
subjects affected / exposed	9 / 67 (13.43%)	4 / 67 (5.97%)	16 / 65 (24.62%)	12 / 66 (18.18%)
occurrences all number	11	4	24	13
Dyspnoea Exertional
subjects affected / exposed	3 / 67 (4.48%)	2 / 67 (2.99%)	2 / 65 (3.08%)	4 / 66 (6.06%)
occurrences all number	3	2	2	4
Epistaxis
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	1	0	0	1
Haemoptysis
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Hiccups
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Orthopnoea
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Lung Disorder
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Nasal Congestion
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	0	2	0
Oropharyngeal Pain
subjects affected / exposed	2 / 67 (2.99%)	1 / 67 (1.49%)	1 / 65 (1.54%)	3 / 66 (4.55%)
occurrences all number	2	1	1	3
Oropharyngeal Spasm
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Hypoxia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Wheezing
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	2	0	0
Upper-Airway Cough Syndrome
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	1	0	1
Pharyngeal Erythema
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Pleural Effusion
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	1	0	0
Pneumothorax
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Productive Cough
subjects affected / exposed	0 / 67 (0.00%)	5 / 67 (7.46%)	2 / 65 (3.08%)	4 / 66 (6.06%)
occurrences all number	0	5	3	5
Pulmonary Congestion
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Pulmonary Oedema
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Respiratory Distress
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Respiratory Failure
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	2	0	0
Rhinitis Allergic
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	0	1	1
Rhinorrhoea
subjects affected / exposed	0 / 67 (0.00%)	3 / 67 (4.48%)	0 / 65 (0.00%)	5 / 66 (7.58%)
occurrences all number	0	4	0	5
Sleep Apnoea Syndrome
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Sneezing
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Upper Respiratory Tract Congestion
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	2 / 66 (3.03%)
occurrences all number	0	0	2	2
Aggression
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Mood Swings
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	0	4	0
Mood Altered
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Psychiatric Decompensation
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Psychotic Disorder
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Restlessness
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	1 / 66 (1.52%)
occurrences all number	0	0	2	1
Sleep Disorder
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	3 / 65 (4.62%)	4 / 66 (6.06%)
occurrences all number	0	2	4	5
Anxiety
subjects affected / exposed	2 / 67 (2.99%)	1 / 67 (1.49%)	4 / 65 (6.15%)	7 / 66 (10.61%)
occurrences all number	3	1	4	8
Confusional State
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	2 / 65 (3.08%)	1 / 66 (1.52%)
occurrences all number	2	0	2	1
Depressed Mood
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	0	1	1
Depression
subjects affected / exposed	0 / 67 (0.00%)	4 / 67 (5.97%)	4 / 65 (6.15%)	2 / 66 (3.03%)
occurrences all number	0	4	5	2
Depressive Symptom
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	1	0	1
Emotional Disorder
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Emotional Distress
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Hallucination
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	1	1	0	1
Insomnia
subjects affected / exposed	12 / 67 (17.91%)	16 / 67 (23.88%)	13 / 65 (20.00%)	23 / 66 (34.85%)
occurrences all number	12	25	23	37
Irritability
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	2 / 65 (3.08%)	4 / 66 (6.06%)
occurrences all number	1	1	2	5
Libido Decreased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	0	2	0
Nervousness
subjects affected / exposed	1 / 67 (1.49%)	2 / 67 (2.99%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	1	2	0	2
Product issues
Device Breakage
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Device Dislocation
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	0	1	1
Investigations
Alanine Aminotransferase Decreased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Blood Lactate Dehydrogenase Increased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	0	0	0	2
Blood Iron Decreased
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Blood Fibrinogen Increased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Blood Creatinine Increased
subjects affected / exposed	2 / 67 (2.99%)	7 / 67 (10.45%)	8 / 65 (12.31%)	2 / 66 (3.03%)
occurrences all number	2	11	13	2
Blood Creatinine Decreased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Activated Partial Thromboplastin Time Prolonged
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Blood Alkaline Phosphatase Increased
subjects affected / exposed	1 / 67 (1.49%)	5 / 67 (7.46%)	3 / 65 (4.62%)	5 / 66 (7.58%)
occurrences all number	1	7	3	10
Aspergillus Test Positive
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Aspartate Aminotransferase Increased
subjects affected / exposed	2 / 67 (2.99%)	4 / 67 (5.97%)	3 / 65 (4.62%)	3 / 66 (4.55%)
occurrences all number	2	6	4	6
Alanine Aminotransferase Increased
subjects affected / exposed	3 / 67 (4.48%)	5 / 67 (7.46%)	4 / 65 (6.15%)	7 / 66 (10.61%)
occurrences all number	3	6	6	16
Blood Creatine Phosphokinase Increased
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	2	0	0
Respiratory Rate Increased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Pain Threshold Decreased
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
N-Terminal Prohormone Brain Natriuretic Peptide Increased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Myoglobin Blood Increased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Intra-Abdominal Pressure Increased
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
International Normalised Ratio Increased
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Gamma-Glutamyltransferase Increased
subjects affected / exposed	1 / 67 (1.49%)	5 / 67 (7.46%)	0 / 65 (0.00%)	8 / 66 (12.12%)
occurrences all number	1	17	0	19
Ejection Fraction Decreased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	0	0	0	2
Clostridium Test Positive
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Cardiac Murmur
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
C-Reactive Protein Increased
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	2 / 65 (3.08%)	2 / 66 (3.03%)
occurrences all number	1	0	3	2
Body Temperature Increased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Blood Urea Increased
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Reticulocyte Count Increased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Blood Pressure Increased
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Weight Increased
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	2	1	0	2
Weight Decreased
subjects affected / exposed	2 / 67 (2.99%)	7 / 67 (10.45%)	8 / 65 (12.31%)	1 / 66 (1.52%)
occurrences all number	2	10	12	1
Troponin I Increased
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Injury, poisoning and procedural complications
Meniscus Cyst
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Animal Bite
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Arthropod Bite
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Clavicle Fracture
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Contusion
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	3 / 65 (4.62%)	0 / 66 (0.00%)
occurrences all number	0	0	5	0
Face Injury
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Ligament Sprain
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Joint Injury
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Joint Dislocation
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Head Injury
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	0	2	0
Hand Fracture
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Fall
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	6 / 65 (9.23%)	0 / 66 (0.00%)
occurrences all number	0	2	10	0
Muscle Rupture
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Muscle Strain
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Post Procedural Complication
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Rib Fracture
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Skin Abrasion
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Skin Laceration
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Spinal Compression Fracture
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	2	0	0	0
Subcutaneous Haematoma
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Sunburn
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Tendon Rupture
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	2	0
Thermal Burn
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Tooth Fracture
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	2	0	1
Wound Dehiscence
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Congenital, familial and genetic disorders
Ichthyosis
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Hydrocele
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Limb Malformation
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Malformation Venous
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	2
Cardiac disorders
Cardiac Septal Hypertrophy
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Palpitations
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	1	0	0	1
Sinus Bradycardia
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	0	1	0
Sinus Tachycardia
subjects affected / exposed	2 / 67 (2.99%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	2	1	1	0
Supraventricular Tachycardia
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	0	1	0
Tachycardia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	2 / 65 (3.08%)	3 / 66 (4.55%)
occurrences all number	0	1	2	5
Cardiac Failure Chronic
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Cardiac Failure
subjects affected / exposed	1 / 67 (1.49%)	3 / 67 (4.48%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	4	1	0
Bundle Branch Block Right
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Bradycardia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Atrial Flutter
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	0	1	0
Atrial Fibrillation
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	1	3	0
Ventricular Pre-Excitation
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Angina Pectoris
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	2	1	0
Nervous system disorders
Ageusia
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	1	1	0
Head Discomfort
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Amnesia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	3 / 65 (4.62%)	0 / 66 (0.00%)
occurrences all number	0	0	3	0
Aphasia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Ataxia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Balance Disorder
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Burning Sensation
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Cauda Equina Syndrome
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Cerebral Small Vessel Ischaemic Disease
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Cervical Radiculopathy
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Cervicobrachial Syndrome
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Cognitive Disorder
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Depressed Level of Consciousness
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Dizziness
subjects affected / exposed	6 / 67 (8.96%)	8 / 67 (11.94%)	9 / 65 (13.85%)	3 / 66 (4.55%)
occurrences all number	6	9	12	5
Dysaesthesia
subjects affected / exposed	2 / 67 (2.99%)	1 / 67 (1.49%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	2	1	0	2
Dysgeusia
subjects affected / exposed	3 / 67 (4.48%)	2 / 67 (2.99%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	3	2	2	0
Allodynia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Headache
subjects affected / exposed	7 / 67 (10.45%)	6 / 67 (8.96%)	5 / 65 (7.69%)	15 / 66 (22.73%)
occurrences all number	7	6	7	23
Piriformis Syndrome
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Hypoaesthesia
subjects affected / exposed	0 / 67 (0.00%)	3 / 67 (4.48%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	3	0	1
Hypogeusia
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Lethargy
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	0	4	0
Leukoencephalopathy
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Loss of Consciousness
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Memory Impairment
subjects affected / exposed	0 / 67 (0.00%)	3 / 67 (4.48%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	3	1	0
Monoparesis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	0	0	0	3
Neuralgia
subjects affected / exposed	2 / 67 (2.99%)	2 / 67 (2.99%)	2 / 65 (3.08%)	2 / 66 (3.03%)
occurrences all number	2	2	2	2
Neuromyopathy
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Neuropathy Peripheral
subjects affected / exposed	1 / 67 (1.49%)	3 / 67 (4.48%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	3	2	0
Paraesthesia
subjects affected / exposed	2 / 67 (2.99%)	9 / 67 (13.43%)	5 / 65 (7.69%)	6 / 66 (9.09%)
occurrences all number	2	11	6	6
Peripheral Motor Neuropathy
subjects affected / exposed	1 / 67 (1.49%)	4 / 67 (5.97%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	10	1	0
Peripheral Sensorimotor Neuropathy
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	5
Peripheral Sensory Neuropathy
subjects affected / exposed	28 / 67 (41.79%)	26 / 67 (38.81%)	14 / 65 (21.54%)	7 / 66 (10.61%)
occurrences all number	42	56	27	14
Hyperaesthesia
subjects affected / exposed	2 / 67 (2.99%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	2	0	0	1
Polyneuropathy
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Psychomotor Hyperactivity
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Radiculopathy
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Resting Tremor
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Restless Legs Syndrome
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	1	1	1
Sciatica
subjects affected / exposed	2 / 67 (2.99%)	3 / 67 (4.48%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	3	4	1	1
Seizure
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Sensory Disturbance
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Somnolence
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	1	1	1
Syncope
subjects affected / exposed	0 / 67 (0.00%)	4 / 67 (5.97%)	3 / 65 (4.62%)	1 / 66 (1.52%)
occurrences all number	0	5	3	1
Taste Disorder
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	2 / 65 (3.08%)	1 / 66 (1.52%)
occurrences all number	0	1	2	1
Tremor
subjects affected / exposed	4 / 67 (5.97%)	3 / 67 (4.48%)	4 / 65 (6.15%)	2 / 66 (3.03%)
occurrences all number	4	3	7	3
Trigeminal Neuralgia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Presyncope
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Blood and lymphatic system disorders
Leukocytosis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Increased Tendency to Bruise
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Febrile Neutropenia
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	1	1	1	1
Bone Marrow Failure
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Leukopenia
subjects affected / exposed	9 / 67 (13.43%)	8 / 67 (11.94%)	11 / 65 (16.92%)	6 / 66 (9.09%)
occurrences all number	20	49	75	38
Anaemia Macrocytic
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Neutropenia
subjects affected / exposed	25 / 67 (37.31%)	30 / 67 (44.78%)	44 / 65 (67.69%)	15 / 66 (22.73%)
occurrences all number	64	138	226	27
Lymphopenia
subjects affected / exposed	13 / 67 (19.40%)	15 / 67 (22.39%)	10 / 65 (15.38%)	12 / 66 (18.18%)
occurrences all number	42	130	64	53
Lymphadenopathy
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Anaemia
subjects affected / exposed	12 / 67 (17.91%)	30 / 67 (44.78%)	26 / 65 (40.00%)	25 / 66 (37.88%)
occurrences all number	19	86	74	58
Thrombocytopenic Purpura
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Thrombocytopenia
subjects affected / exposed	25 / 67 (37.31%)	38 / 67 (56.72%)	23 / 65 (35.38%)	34 / 66 (51.52%)
occurrences all number	68	179	95	175
Neutrophilia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	3
Ear and labyrinth disorders
Vertigo Positional
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Vertigo
subjects affected / exposed	1 / 67 (1.49%)	2 / 67 (2.99%)	0 / 65 (0.00%)	6 / 66 (9.09%)
occurrences all number	1	2	0	8
Tympanic Membrane Perforation
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Tinnitus
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	1 / 65 (1.54%)	2 / 66 (3.03%)
occurrences all number	1	1	1	3
Meniere's Disease
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Hypoacusis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	2	1	0
Eustachian Tube Dysfunction
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Ear Pain
subjects affected / exposed	1 / 67 (1.49%)	2 / 67 (2.99%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	2	1	0
Ear Discomfort
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Deafness Neurosensory
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Deafness
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Eye disorders
Dry Age-Related Macular Degeneration
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Diplopia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Corneal Oedema
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Corneal Disorder
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	2	0	0
Conjunctivitis Allergic
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Conjunctival Irritation
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Conjunctival Hyperaemia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Conjunctival Haemorrhage
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	0	0	0	2
Chalazion
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	4	0	0
Cataract Nuclear
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Cataract Cortical
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Cataract
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	11 / 65 (16.92%)	2 / 66 (3.03%)
occurrences all number	0	1	13	2
Blepharitis
subjects affected / exposed	1 / 67 (1.49%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	2	0	0
Keratitis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Lens Dislocation
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Macular Degeneration
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Macular Hole
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Ocular Discomfort
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Periorbital Swelling
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Retinal Detachment
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	3
Retinal Vein Occlusion
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Vision Blurred
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	2 / 65 (3.08%)	1 / 66 (1.52%)
occurrences all number	1	1	2	1
Visual Impairment
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	0	1	1
Vitreoretinal Traction Syndrome
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Dry Eye
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	2	2	0
Eye Discharge
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Eye Pain
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Eyelid Ptosis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Foreign Body Sensation in Eyes
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal disorders
Abdominal Discomfort
subjects affected / exposed	1 / 67 (1.49%)	4 / 67 (5.97%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	1	6	0	2
Abdominal Distension
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	1	1	1
Abdominal Hernia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Faecal Vomiting
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Abdominal Pain Upper
subjects affected / exposed	2 / 67 (2.99%)	4 / 67 (5.97%)	3 / 65 (4.62%)	4 / 66 (6.06%)
occurrences all number	2	4	3	5
Aerophagia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Anal Fissure
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Aphthous Ulcer
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Bile Acid Malabsorption
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Chronic Gastritis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Constipation
subjects affected / exposed	26 / 67 (38.81%)	30 / 67 (44.78%)	21 / 65 (32.31%)	6 / 66 (9.09%)
occurrences all number	30	39	28	6
Dental Caries
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	2	1	0
Diarrhoea
subjects affected / exposed	16 / 67 (23.88%)	23 / 67 (34.33%)	32 / 65 (49.23%)	20 / 66 (30.30%)
occurrences all number	20	37	68	30
Diarrhoea Haemorrhagic
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Dry Mouth
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	2	2	0
Dyspepsia
subjects affected / exposed	2 / 67 (2.99%)	4 / 67 (5.97%)	1 / 65 (1.54%)	2 / 66 (3.03%)
occurrences all number	2	4	1	2
Dysphagia
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	1	1	0	2
Epigastric Discomfort
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	1	0	1
Abdominal Pain
subjects affected / exposed	3 / 67 (4.48%)	9 / 67 (13.43%)	3 / 65 (4.62%)	4 / 66 (6.06%)
occurrences all number	4	9	4	4
Faeces Discoloured
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	0	1	0
Intestinal Obstruction
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Food Poisoning
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Gastric Disorder
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Gastritis
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	3	0	1
Gastrointestinal Disorder
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Gastrointestinal Motility Disorder
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Gastrooesophageal Reflux Disease
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	3 / 66 (4.55%)
occurrences all number	0	0	0	3
Gingival Bleeding
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Gingival Discomfort
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Gingival Pain
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Gingival Ulceration
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Haematochezia
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Haemorrhoidal Haemorrhage
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Haemorrhoids
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	1 / 66 (1.52%)
occurrences all number	0	0	2	1
Hypoaesthesia Teeth
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Infrequent Bowel Movements
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Flatulence
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	1	0	0
Swollen Tongue
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Stomatitis
subjects affected / exposed	2 / 67 (2.99%)	4 / 67 (5.97%)	3 / 65 (4.62%)	0 / 66 (0.00%)
occurrences all number	2	5	3	0
Intra-Abdominal Haematoma
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Irritable Bowel Syndrome
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Melaena
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Mouth Cyst
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Mouth Haemorrhage
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	1	0	0	1
Mouth Ulceration
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	1	0	0
Nausea
subjects affected / exposed	12 / 67 (17.91%)	23 / 67 (34.33%)	8 / 65 (12.31%)	17 / 66 (25.76%)
occurrences all number	14	32	11	28
Noninfective Gingivitis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	2
Odynophagia
subjects affected / exposed	3 / 67 (4.48%)	2 / 67 (2.99%)	2 / 65 (3.08%)	4 / 66 (6.06%)
occurrences all number	3	2	2	5
Oesophagitis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	3
Oral Dysaesthesia
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Oral Pain
subjects affected / exposed	2 / 67 (2.99%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	2	0	1	0
Paraesthesia Oral
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Proctalgia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Rectal Haemorrhage
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Tooth Disorder
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Toothache
subjects affected / exposed	2 / 67 (2.99%)	0 / 67 (0.00%)	2 / 65 (3.08%)	2 / 66 (3.03%)
occurrences all number	2	0	2	2
Vomiting
subjects affected / exposed	6 / 67 (8.96%)	14 / 67 (20.90%)	7 / 65 (10.77%)	11 / 66 (16.67%)
occurrences all number	10	16	9	14
Upper Gastrointestinal Haemorrhage
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Hepatobiliary disorders
Biliary Colic
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Hepatic Function Abnormal
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	2 / 66 (3.03%)
occurrences all number	0	7	1	2
Cholestasis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Cholelithiasis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	0	2	0
Liver Disorder
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	0	3	0
Hypertransaminasaemia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	6
Hyperbilirubinaemia
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	2 / 65 (3.08%)	1 / 66 (1.52%)
occurrences all number	1	0	2	3
Hepatotoxicity
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	1	0	1
Hepatocellular Injury
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	4	0	1	0
Skin and subcutaneous tissue disorders
Actinic Keratosis
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	3	0	0
Alopecia
subjects affected / exposed	1 / 67 (1.49%)	3 / 67 (4.48%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	3	1	0
Petechiae
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Dermatitis Diaper
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Dermatitis Exfoliative Generalised
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Drug Eruption
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Ecchymosis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Erythema
subjects affected / exposed	4 / 67 (5.97%)	7 / 67 (10.45%)	2 / 65 (3.08%)	5 / 66 (7.58%)
occurrences all number	4	7	2	8
Haemorrhage Subcutaneous
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	2	0	0
Hirsutism
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Hyperhidrosis
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	2 / 65 (3.08%)	1 / 66 (1.52%)
occurrences all number	1	1	2	1
Hyperkeratosis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Intertrigo
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	3	0
Macule
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Night Sweats
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Pain of Skin
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Dermatitis Allergic
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Pruritus
subjects affected / exposed	4 / 67 (5.97%)	8 / 67 (11.94%)	3 / 65 (4.62%)	6 / 66 (9.09%)
occurrences all number	5	11	3	8
Urticaria
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	0	1	0
Rash
subjects affected / exposed	9 / 67 (13.43%)	11 / 67 (16.42%)	10 / 65 (15.38%)	6 / 66 (9.09%)
occurrences all number	12	17	12	9
Rash Erythematous
subjects affected / exposed	2 / 67 (2.99%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	2	0	1	0
Rash Generalised
subjects affected / exposed	4 / 67 (5.97%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	4	0	0	0
Rash Macular
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	2
Rash Maculo-Papular
subjects affected / exposed	3 / 67 (4.48%)	4 / 67 (5.97%)	4 / 65 (6.15%)	1 / 66 (1.52%)
occurrences all number	8	8	6	1
Rash Pruritic
subjects affected / exposed	3 / 67 (4.48%)	3 / 67 (4.48%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	4	4	0	1
Rosacea
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Segmented Hyalinising Vasculitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Sensitive Skin
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Skin Lesion
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	2	2	0
Skin Mass
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	0	2	0
Skin Reaction
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	2	0	0	0
Skin Ulcer
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	2	0
Swelling Face
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	2	0
Toxic Skin Eruption
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Psoriasis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Renal and urinary disorders
Acute Kidney Injury
subjects affected / exposed	1 / 67 (1.49%)	3 / 67 (4.48%)	4 / 65 (6.15%)	1 / 66 (1.52%)
occurrences all number	1	8	6	1
Urinary Retention
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	2	1	1
Chronic Kidney Disease
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	2	0	1
Cystitis Noninfective
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Dysuria
subjects affected / exposed	0 / 67 (0.00%)	3 / 67 (4.48%)	0 / 65 (0.00%)	3 / 66 (4.55%)
occurrences all number	0	4	0	5
Haematuria
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	2	1	0
Hydronephrosis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Ketonuria
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Nocturia
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	2	1	0
Oliguria
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	1	0	1
Pollakiuria
subjects affected / exposed	1 / 67 (1.49%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	2	0	0
Renal Colic
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Renal Failure
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	3 / 65 (4.62%)	2 / 66 (3.03%)
occurrences all number	0	2	5	2
Renal Impairment
subjects affected / exposed	1 / 67 (1.49%)	2 / 67 (2.99%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	1	2	3	0
Urethral Haemorrhage
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Urinary Incontinence
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Bladder Pain
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Urinary Tract Obstruction
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Endocrine disorders
Adrenal Insufficiency
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Cushing's Syndrome
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Thyroid Mass
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Goitre
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Musculoskeletal and connective tissue disorders
Amyotrophy
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Arthralgia
subjects affected / exposed	1 / 67 (1.49%)	15 / 67 (22.39%)	10 / 65 (15.38%)	13 / 66 (19.70%)
occurrences all number	1	23	21	15
Arthritis
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	2	0	0
Arthropathy
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Back Pain
subjects affected / exposed	7 / 67 (10.45%)	19 / 67 (28.36%)	14 / 65 (21.54%)	11 / 66 (16.67%)
occurrences all number	8	30	17	14
Bone Pain
subjects affected / exposed	0 / 67 (0.00%)	5 / 67 (7.46%)	1 / 65 (1.54%)	7 / 66 (10.61%)
occurrences all number	0	5	1	8
Cervical Spinal Stenosis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Flank Pain
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	1	0	1
Foot Deformity
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Fracture Pain
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Groin Pain
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	1	0	0
Haematoma Muscle
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	1	2	0
Hypercreatinaemia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Intervertebral Disc Disorder
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	0	1	1
Joint Effusion
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Joint Range of Motion Decreased
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Joint Stiffness
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Joint Swelling
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Osteonecrosis of Jaw
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	2	0
Metatarsalgia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Osteitis
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	4	0	0
Neck Pain
subjects affected / exposed	2 / 67 (2.99%)	1 / 67 (1.49%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	2	1	1	1
Myopathy
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	2	0	1	0
Myalgia
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	4 / 65 (6.15%)	2 / 66 (3.03%)
occurrences all number	0	2	6	4
Musculoskeletal Stiffness
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	1	1	0	1
Musculoskeletal Pain
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	1	1	0
Musculoskeletal Discomfort
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Musculoskeletal Chest Pain
subjects affected / exposed	1 / 67 (1.49%)	8 / 67 (11.94%)	6 / 65 (9.23%)	7 / 66 (10.61%)
occurrences all number	1	9	8	7
Muscular Weakness
subjects affected / exposed	2 / 67 (2.99%)	4 / 67 (5.97%)	3 / 65 (4.62%)	1 / 66 (1.52%)
occurrences all number	3	4	3	1
Muscle Tightness
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Muscle Spasms
subjects affected / exposed	4 / 67 (5.97%)	4 / 67 (5.97%)	21 / 65 (32.31%)	7 / 66 (10.61%)
occurrences all number	4	4	36	9
Muscle Discomfort
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Muscle Contracture
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Muscle Atrophy
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	0	4	0
Osteoarthritis
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	2	1	1
Trismus
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Tendonitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Tendon Disorder
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Synovial Cyst
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Spinal Pain
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	3 / 65 (4.62%)	6 / 66 (9.09%)
occurrences all number	1	0	3	6
Rotator Cuff Syndrome
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Pain in Jaw
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	1	1	1
Pain in Extremity
subjects affected / exposed	6 / 67 (8.96%)	11 / 67 (16.42%)	3 / 65 (4.62%)	4 / 66 (6.06%)
occurrences all number	6	11	6	7
Osteoporosis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Infections and infestations
Bacterial Infection
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Acarodermatitis
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Balanitis Candida
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Conjunctivitis
subjects affected / exposed	2 / 67 (2.99%)	5 / 67 (7.46%)	4 / 65 (6.15%)	3 / 66 (4.55%)
occurrences all number	2	5	4	5
Clostridium Difficile Infection
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Clostridium Difficile Colitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Clostridium Colitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Citrobacter Infection
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Cellulitis Orbital
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Cellulitis
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	3 / 65 (4.62%)	1 / 66 (1.52%)
occurrences all number	1	0	4	2
Candida Infection
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	1	0	1
Campylobacter Infection
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Campylobacter Gastroenteritis
subjects affected / exposed	1 / 67 (1.49%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	1	0	0
Bronchitis Viral
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	0	1	1
Bronchitis
subjects affected / exposed	2 / 67 (2.99%)	17 / 67 (25.37%)	10 / 65 (15.38%)	7 / 66 (10.61%)
occurrences all number	2	28	19	7
Body Tinea
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Covid-19
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	0	1	0	2
Herpes Virus Infection
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Cytomegalovirus Infection Reactivation
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	3	0	0
Ear Infection
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	2	0	0
Herpes Dermatitis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Hepatitis E
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Gingivitis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Genital Infection
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal Infection
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Gastroenteritis Viral
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Gastroenteritis
subjects affected / exposed	1 / 67 (1.49%)	7 / 67 (10.45%)	2 / 65 (3.08%)	3 / 66 (4.55%)
occurrences all number	1	7	3	3
Gastritis Viral
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Folliculitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Eye Infection
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	1	0	2	0
Escherichia Urinary Tract Infection
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	3	0	1
Escherichia Pyelonephritis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Erysipelas
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Cystitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	3	0
Hordeolum
subjects affected / exposed	2 / 67 (2.99%)	3 / 67 (4.48%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	3	5	1	0
Impetigo
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	3	0
Infected Skin Ulcer
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Infection
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	4 / 65 (6.15%)	3 / 66 (4.55%)
occurrences all number	0	0	4	3
Infection Parasitic
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Infective Exacerbation of Chronic Obstructive Airways Disease
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Influenza
subjects affected / exposed	1 / 67 (1.49%)	3 / 67 (4.48%)	3 / 65 (4.62%)	3 / 66 (4.55%)
occurrences all number	1	3	3	3
Klebsiella Infection
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Lower Respiratory Tract Infection
subjects affected / exposed	3 / 67 (4.48%)	1 / 67 (1.49%)	2 / 65 (3.08%)	3 / 66 (4.55%)
occurrences all number	3	1	4	3
Metapneumovirus Infection
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Nasopharyngitis
subjects affected / exposed	2 / 67 (2.99%)	16 / 67 (23.88%)	8 / 65 (12.31%)	17 / 66 (25.76%)
occurrences all number	3	21	11	24
Omphalitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Oral Candidiasis
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	2	1	1
Oral Fungal Infection
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Oral Herpes
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	0	1	1
Otitis Externa
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Herpes Zoster
subjects affected / exposed	0 / 67 (0.00%)	6 / 67 (8.96%)	2 / 65 (3.08%)	1 / 66 (1.52%)
occurrences all number	0	7	2	1
Respiratory Syncytial Virus Infection
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Pulpitis Dental
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Postoperative Wound Infection
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Pneumonia Bacterial
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Pneumonia
subjects affected / exposed	3 / 67 (4.48%)	6 / 67 (8.96%)	9 / 65 (13.85%)	2 / 66 (3.03%)
occurrences all number	3	7	13	2
Respiratory Tract Infection Viral
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	0	1	1
Periodontitis
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	3	0	0
Paronychia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	1	0	2
Parainfluenzae Virus Infection
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	1	0	1
Otitis Media
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Respiratory Tract Infection
subjects affected / exposed	1 / 67 (1.49%)	3 / 67 (4.48%)	2 / 65 (3.08%)	3 / 66 (4.55%)
occurrences all number	1	3	2	4
Pharyngitis
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	2 / 65 (3.08%)	3 / 66 (4.55%)
occurrences all number	0	2	2	3
Tooth Infection
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	0	1	1
Tooth Abscess
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	1 / 66 (1.52%)
occurrences all number	0	0	2	2
Tonsillitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	1	0	1
Tongue Fungal Infection
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Tinea Infection
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Skin Infection
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	1	1	0
Sinusitis
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	2 / 65 (3.08%)	1 / 66 (1.52%)
occurrences all number	0	2	2	1
Sepsis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Rhinovirus Infection
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Rhinitis
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	7 / 65 (10.77%)	5 / 66 (7.58%)
occurrences all number	0	4	9	7
Tracheitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Viral Infection
subjects affected / exposed	3 / 67 (4.48%)	0 / 67 (0.00%)	3 / 65 (4.62%)	0 / 66 (0.00%)
occurrences all number	3	0	3	0
Urinary Tract Infection Fungal
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Urinary Tract Infection Bacterial
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	3	0	0
Urinary Tract Infection
subjects affected / exposed	0 / 67 (0.00%)	9 / 67 (13.43%)	8 / 65 (12.31%)	2 / 66 (3.03%)
occurrences all number	0	11	10	2
Upper Respiratory Tract Infection Bacterial
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Upper Respiratory Tract Infection
subjects affected / exposed	5 / 67 (7.46%)	19 / 67 (28.36%)	20 / 65 (30.77%)	12 / 66 (18.18%)
occurrences all number	5	34	32	19
Viral Pharyngitis
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Viral Rhinitis
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Viral Upper Respiratory Tract Infection
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	2
Vulvovaginal Mycotic Infection
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	3	0	0
Viral Rash
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Metabolism and nutrition disorders
Cachexia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	2	0	0
Hyperkalaemia
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	3 / 65 (4.62%)	0 / 66 (0.00%)
occurrences all number	0	4	4	0
Hyperglycaemia
subjects affected / exposed	1 / 67 (1.49%)	2 / 67 (2.99%)	9 / 65 (13.85%)	7 / 66 (10.61%)
occurrences all number	3	3	31	13
Hypercreatininaemia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	1	1	1
Hypercholesterolaemia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Hypercalcaemia
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	2	0	1
Hyperamylasaemia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Gout
subjects affected / exposed	0 / 67 (0.00%)	2 / 67 (2.99%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	2	1	0
Fluid Retention
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	1	3	2
Fluid Overload
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Diabetic Metabolic Decompensation
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	0	2	0
Diabetes Mellitus Inadequate Control
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Diabetes Mellitus
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Decreased Appetite
subjects affected / exposed	2 / 67 (2.99%)	13 / 67 (19.40%)	4 / 65 (6.15%)	4 / 66 (6.06%)
occurrences all number	2	18	6	6
Hypernatraemia
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Vitamin B12 Deficiency
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	0	1	0	6
Hyperuricaemia
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	2 / 65 (3.08%)	1 / 66 (1.52%)
occurrences all number	0	2	2	1
Type 2 Diabetes Mellitus
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0
Steroid Diabetes
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	2 / 65 (3.08%)	0 / 66 (0.00%)
occurrences all number	0	0	2	0
Malnutrition
subjects affected / exposed	1 / 67 (1.49%)	0 / 67 (0.00%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	1	0	0	0
Iron Deficiency
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	1 / 66 (1.52%)
occurrences all number	0	0	1	1
Increased Appetite
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	1
Hypophosphataemia
subjects affected / exposed	1 / 67 (1.49%)	4 / 67 (5.97%)	4 / 65 (6.15%)	0 / 66 (0.00%)
occurrences all number	1	6	20	0
Hyponatraemia
subjects affected / exposed	1 / 67 (1.49%)	3 / 67 (4.48%)	0 / 65 (0.00%)	2 / 66 (3.03%)
occurrences all number	1	5	0	4
Hypomagnesaemia
subjects affected / exposed	2 / 67 (2.99%)	0 / 67 (0.00%)	5 / 65 (7.69%)	2 / 66 (3.03%)
occurrences all number	2	0	11	2
Hypokalaemia
subjects affected / exposed	2 / 67 (2.99%)	7 / 67 (10.45%)	10 / 65 (15.38%)	2 / 66 (3.03%)
occurrences all number	2	8	28	4
Hypoglycaemia
subjects affected / exposed	2 / 67 (2.99%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	3	0	6	0
Hypoferritinaemia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	1 / 65 (1.54%)	0 / 66 (0.00%)
occurrences all number	0	0	1	0
Hypocalcaemia
subjects affected / exposed	5 / 67 (7.46%)	6 / 67 (8.96%)	9 / 65 (13.85%)	4 / 66 (6.06%)
occurrences all number	5	11	23	6
Hypoalbuminaemia
subjects affected / exposed	2 / 67 (2.99%)	0 / 67 (0.00%)	4 / 65 (6.15%)	0 / 66 (0.00%)
occurrences all number	3	0	4	0
Hyperphosphataemia
subjects affected / exposed	0 / 67 (0.00%)	0 / 67 (0.00%)	0 / 65 (0.00%)	1 / 66 (1.52%)
occurrences all number	0	0	0	2
Vitamin D Deficiency
subjects affected / exposed	0 / 67 (0.00%)	1 / 67 (1.49%)	0 / 65 (0.00%)	0 / 66 (0.00%)
occurrences all number	0	1	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

06 Jun 2018

The purpose of this amendment-1 was to include address Health Authority requests and to correct administrative errors and inconsistencies in the original protocol.

12 Oct 2018

The purpose of this amendment-2 was to add a cohort to explore the efficacy and safety of daratumumab subcutaneous (SC) in combination with carfilzomib and dexamethasone (D-Kd).

31 Jan 2019

The purpose of this amendment-3 was to identification of a new important risk (hepatitis B virus reactivation).

28 Jan 2020

The purpose of this amendment-4 was to clarify the timing of the primary analysis for the D-Kd cohort and the end of study and to align language for anticipated events and pregnancy/contraception with the daratumumab program standard.

30 Sep 2020

The purpose of this amendment-5 was to define when the clinical cutoff for the final analysis occurred which marks the end of data collection, to define the end of study, and to clarify access to study drugs for subjects who continued to receive study treatment after data collection has ended.

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 Multicenter Phase 2 Study to Evaluate Subcutaneous Daratumumab in Combination with Standard Multiple Myeloma Treatment Regimens

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)

Primary: D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)

Primary: D-VRd Cohort: Percentage of Subjects With Very Good Partial Response (VGPR) or Better Response

Primary: D-VRd Cohort: Percentage of Subjects With Very Good Partial Response (VGPR) or Better Response

Secondary: Maximum Observed Serum Concentration (Cmax) of Daratumumab

Secondary: Maximum Observed Serum Concentration (Cmax) of Daratumumab

Secondary: D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Subjects With VGPR or Better Response

Secondary: D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Subjects With VGPR or Better Response

Secondary: Percentage of Subjects with Infusion-Related Reactions (IRRs)

Secondary: Percentage of Subjects with Infusion-Related Reactions (IRRs)

Secondary: D-VRd Cohort: Overall Response Rate (ORR)

Secondary: D-VRd Cohort: Overall Response Rate (ORR)

Secondary: Percentage of Subjects With CR or Better Response

Secondary: Percentage of Subjects With CR or Better Response

Secondary: D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)

Secondary: D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)

Secondary: Percentage of Subjects with Anti-Daratumumab Antibodies

Secondary: Percentage of Subjects with Anti-Daratumumab Antibodies

Secondary: Percentage of Subjects with Anti-rHuPH20 Antibodies

Secondary: Percentage of Subjects with Anti-rHuPH20 Antibodies

Secondary: D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Subjects with Minimal Residual Disease (MRD) Negative Rate

Secondary: D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Subjects with Minimal Residual Disease (MRD) Negative Rate

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Outside EU/EEA

Clinical trials

Clinical Trial Results: A Multicenter Phase 2 Study to Evaluate Subcutaneous Daratumumab in Combination with Standard Multiple Myeloma Treatment Regimens

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)

Primary: D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)

Primary: D-VRd Cohort: Percentage of Subjects With Very Good Partial Response (VGPR) or Better Response

Primary: D-VRd Cohort: Percentage of Subjects With Very Good Partial Response (VGPR) or Better Response

Secondary: Maximum Observed Serum Concentration (Cmax) of Daratumumab

Secondary: Maximum Observed Serum Concentration (Cmax) of Daratumumab

Secondary: D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Subjects With VGPR or Better Response

Secondary: D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Subjects With VGPR or Better Response

Secondary: Percentage of Subjects with Infusion-Related Reactions (IRRs)

Secondary: Percentage of Subjects with Infusion-Related Reactions (IRRs)

Secondary: D-VRd Cohort: Overall Response Rate (ORR)

Secondary: D-VRd Cohort: Overall Response Rate (ORR)

Secondary: Percentage of Subjects With CR or Better Response

Secondary: Percentage of Subjects With CR or Better Response

Secondary: D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)

Secondary: D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)

Secondary: Percentage of Subjects with Anti-Daratumumab Antibodies

Secondary: Percentage of Subjects with Anti-Daratumumab Antibodies

Secondary: Percentage of Subjects with Anti-rHuPH20 Antibodies

Secondary: Percentage of Subjects with Anti-rHuPH20 Antibodies

Secondary: D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Subjects with Minimal Residual Disease (MRD) Negative Rate

Secondary: D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Subjects with Minimal Residual Disease (MRD) Negative Rate

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Multicenter Phase 2 Study to Evaluate Subcutaneous Daratumumab in Combination with Standard Multiple Myeloma Treatment Regimens