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Clinical Trial Results:
A Phase 1/2 Dose Escalation Safety, Pharmacokinetic and Efficacy Study of Multiple Intravenous Administrations of a Humanized Monoclonal Antibody (SAR650984) Against CD38 in Patients With Selected CD38+ Hematological Malignancies

Summary
EudraCT number	2013-001418-13
Trial protocol	IT GR GB FI BE AT
Global end of trial date	13 Jul 2023

Results information
Results version number	v2(current)
This version publication date	07 Nov 2024
First version publication date	14 Jul 2024
Other versions	v1
Version creation reason	Correction of full data set Align with ClinicalTrials.gov

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

TED10893

ISRCTN number

US NCT number

NCT01084252

WHO universal trial number (UTN)

U1111-1116-5472

Sponsor organisation name

Sanofi aventis recherche & développement

Sponsor organisation address

1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380

Public contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Scientific contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.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

02 Aug 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

13 Jul 2023

Was the trial ended prematurely?

Main objective of the trial

Phase 1: To determine the maximum tolerated/administered dose (MTD/MAD) of isatuximab according to the investigational product (IP)-related dose limiting toxicities (DLTs) observed in participants with cluster of differentiation (CD)38+-selected hematological malignancies. Phase 2 Stage 1: To evaluate the activity of single agent isatuximab at different doses/schedules and to select dose and regimen for Phase 2 Stage 2. Phase 2 Stage 2: To further evaluate the activity in terms of overall response rate (ORR) of isatuximab (SAR650984) at the selected dose/schedule from Stage 1, as single agent (isatuximab arm) and in combination with dexamethasone in participants with relapsed or relapsed/refractory multiple myeloma (RRMM)

Protection of trial subjects

Participants were fully informed of all pertinent aspects of clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the participant and considering the local culture. During the course of the trail, participants were provided with individual participant cards indicating the nature of the trial the participant is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.

Background therapy

Evidence for comparator

Actual start date of recruitment

11 May 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 5

Country: Number of subjects enrolled

Belgium: 4

Country: Number of subjects enrolled

Brazil: 17

Country: Number of subjects enrolled

Chile: 6

Country: Number of subjects enrolled

Finland: 10

Country: Number of subjects enrolled

France: 12

Country: Number of subjects enrolled

Greece: 21

Country: Number of subjects enrolled

Israel: 3

Country: Number of subjects enrolled

Italy: 15

Country: Number of subjects enrolled

Mexico: 5

Country: Number of subjects enrolled

Peru: 7

Country: Number of subjects enrolled

Russian Federation: 13

Country: Number of subjects enrolled

Spain: 16

Country: Number of subjects enrolled

Türkiye: 9

Country: Number of subjects enrolled

Ukraine: 7

Country: Number of subjects enrolled

United Kingdom: 9

Country: Number of subjects enrolled

United States: 191

Worldwide total number of subjects

350

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

168

From 65 to 84 years

179

85 years and over

Subject disposition

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Recruitment details

Study participants were involved in the study from 11 May 2010 at 59 centers in 18 countries. A total of 418 participants were screened, of which 351 participants were enrolled. A total of 67 participants had screen failures due to failure to meet inclusion criteria. 1 participant was enrolled but not treated.

Screening details

Study consisted 2 phases;Phase 1=dose escalation part of isatuximab to determine MTD. Phase 2=for efficacy and safety evaluation of isatuximab with or without dexamethasone. It consisted of 2 stages: Stage 1 (comprised of 1a and 1b) and Stage 2. Here Completed'=Participants with end of treatment or death from any cause forms completed.

Period 1 title

Overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Phase1: Isatuximab <=1 mg/kg every 2 weeks (Q2W)

Arm description

Participants with CD38+ hematological malignancies (HM), received Isatuximab at any one of the dose less than or equal to (<=) 1 milligram per kilogram (mg/kg) (i.e. either 0.0001 mg/kg or 0.001 mg/kg or 0.01 mg/kg or 0.03 mg/kg, or 0.1 mg/kg or 0.3 mg/kg or 1 mg/kg) as intravenous (IV) infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal by participant, investigator’s decision, and/or availability of study drug.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab <=1 mg/kg was administered by IV infusion every week or Q2W in 14-day cycles until protocol defined discontinuation criteria was met.

Phase 1: Isatuximab 3mg/kg Q2W

Arm description

Participants with CD38+ HM, received Isatuximab 3 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator’s decision, and/or availability of study drug.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab 3 mg/kg was administered by IV infusion every week or Q2W in 14-day cycles until protocol defined discontinuation criteria was met.

Phase 1: Isatuximab 5 mg/kg Q2W

Arm description

Participants with CD38+ HM, received Isatuximab 5 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator’s decision, and/or availability of study drug.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab 5 mg/kg was administered by IV infusion every week or Q2W in 14-day cycles until protocol defined discontinuation criteria was met.

Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)

Arm description

Participants with CD38+ HM along with participants with standard risk multiple myeloma were included in this arm and, received Isatuximab 10 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator’s decision, and/or availability of study drug.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab 10 mg/kg was administered by IV infusion on Day 1 of each 14-day cycle until protocol defined discontinuation criteria was met.

Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)

Arm description

Participants with CD38+ HM along with participants with high risk multiple myeloma were included in this arm and, received Isatuximab 10 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator’s decision, and/or availability of study drug.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab 10 mg/kg was administered by IV infusion on Day 1 of each 14-day cycle until protocol defined discontinuation criteria was met.

Phase 1: Isatuximab 10 mg/kg Every Week (QW)

Arm description

Participants with CD38+ HM, received Isatuximab 10 mg/kg, as IV infusion QW, i.e. on Day 1 and 8 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator’s decision, and/or availability of study drug.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab 10 mg/kg was administered by IV infusion on Day 1 and 8 of each 14-day cycle until protocol defined discontinuation criteria was met.

Phase 1: Isatuximab 20 mg/kg Q2W

Arm description

Participants with CD38+ HM, received Isatuximab 20 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator’s decision, and/or availability of study drug.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab 20 mg/kg was administered by IV infusion on Day 1 of each 14-day cycle until protocol defined discontinuation criteria was met.

Phase 1: Isatuximab 20 mg/kg QW

Arm description

Participants with CD38+ HM, received Isatuximab 20 mg/kg, as IV infusion QW, i.e. on Day 1 and 8 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator’s decision, and/or availability of study drug.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab 20 mg/kg was administered by IV infusion on Day 1 and 8 of each 14-day cycle until protocol defined discontinuation criteria was met.

Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W

Arm description

Participants with multiple Myeloma received Isatuximab 3 mg/kg, as IV infusion on Day 1 and Day 15 of each 28-day cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab 3 mg/kg was administered by IV infusion on Day 1 and 15 of each 28-day cycle until protocol defined discontinuation criteria was met.

Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W

Arm description

Participants with multiple Myeloma received Isatuximab 10 mg/kg, as IV infusion on Day 1 and Day 15 of each 28-day cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab 10 mg/kg was administered by IV infusion on Day 1 and 15 of each 28-day cycle until protocol defined discontinuation criteria was met.

Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W

Arm description

Participants with multiple Myeloma received Isatuximab 10 mg/kg, as IV infusion Q2W, i.e. on Day 1 and Day 15 of Cycle 1 and 2 (each cycle 28 days), then every 4 weeks (Q4W), i.e. on Day 1 of each 28-days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab 10 mg/kg was administered by IV infusion on Day 1 and 15 of Cycle 1 and 2 (each cycle 28 days) then Q4W on Day 1 of each 28-day cycle until protocol defined discontinuation criteria was met.

Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W

Arm description

Participants with multiple Myeloma received Isatuximab 20 mg/kg, as IV infusion QW, i.e. on Day 1, 8, 15 and 22 of Cycle 1 and 2 (each cycle 28 days), then Q2W, i.e. on Day 1 and Day 15 of each 28-days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab 20 mg/kg was administered by IV infusion on Days 1, 8, 15 and 22 of Cycle 1 and 2 (each cycle 28 days) then Q2W on Days 1 and 15 of each 28-day cycle until protocol defined discontinuation criteria was met.

Phase 2 Stage 2: Isatuximab alone

Arm description

Participants with relapsed or RRMM, received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator’s decision.

Arm type

Experimental

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Isatuximab 20 mg/kg was administered by IV infusion on Days 1, 8, 15 and 22 of Cycle 1 (28 days) then on Days 1 and 15 of each subsequent 28-day cycle until protocol defined discontinuation criteria was met.

Phase 2 Stage 2: Isatuximab + Dexamethasone

Arm description

Participants with relapsed or RRMM, received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles along with dexamethasone: tablet or as IV infusion (40 mg/day for less than [<] 75 years of age; 20 mg/day for greater than or equal to [>=] 75 years of age) on Days 1, 8, 15 and 22 of each 28 days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator’s decision.

Arm type

Experimental

Investigational medicinal product name

Dexamethasone

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion, Tablet

Routes of administration

Oral use, Intravenous use

Dosage and administration details

Dexamethasone was administered (40 mg/day for <75 years of age; 20 mg/day for >=75 years of age) on Days 1, 8, 15 and 22 of each 28-day cycle until protocol defined discontinuation criteria was met.

Investigational medicinal product name

Isatuximab

Investigational medicinal product code

SAR650984

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 1	Phase1: Isatuximab <=1 mg/kg every 2 weeks (Q2W)	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW	Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W	Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Started	16	6	3	26	18	6	7	7	23	24	25	25	109	55
All Treated (AT) population	16	6	3	26	18	6	7	7	23	24	25	25	109	55
Completed	16	6	3	26	18	6	7	7	23	24	25	25	109	55

Baseline characteristics

Top of page

Reporting group title

Phase1: Isatuximab <=1 mg/kg every 2 weeks (Q2W)

Reporting group description

Reporting group title

Phase 1: Isatuximab 3mg/kg Q2W

Reporting group description

Reporting group title

Phase 1: Isatuximab 5 mg/kg Q2W

Reporting group description

Reporting group title

Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)

Reporting group description

Reporting group title

Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)

Reporting group description

Reporting group title

Phase 1: Isatuximab 10 mg/kg Every Week (QW)

Reporting group description

Reporting group title

Phase 1: Isatuximab 20 mg/kg Q2W

Reporting group description

Reporting group title

Phase 1: Isatuximab 20 mg/kg QW

Reporting group description

Reporting group title

Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W

Reporting group description

Reporting group title

Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W

Reporting group description

Reporting group title

Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W

Reporting group description

Reporting group title

Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W

Reporting group description

Reporting group title

Phase 2 Stage 2: Isatuximab alone

Reporting group description

Participants with relapsed or RRMM, received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator’s decision.

Reporting group title

Phase 2 Stage 2: Isatuximab + Dexamethasone

Reporting group description

Participants with relapsed or RRMM, received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles along with dexamethasone: tablet or as IV infusion (40 mg/day for less than [<] 75 years of age; 20 mg/day for greater than or equal to [>=] 75 years of age) on Days 1, 8, 15 and 22 of each 28 days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator’s decision.

Reporting group values	Phase1: Isatuximab <=1 mg/kg every 2 weeks (Q2W)	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW	Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W	Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone	Total
Number of subjects	16	6	3	26	18	6	7	7	23	24	25	25	109	55	350
Age categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	64.9 ( 11.6 )	63.5 ( 6.2 )	62.0 ( 3.5 )	65.0 ( 7.2 )	60.8 ( 12.6 )	61.7 ( 12.7 )	63.3 ( 10.0 )	60.0 ( 8.3 )	63.2 ( 8.9 )	63.9 ( 8.8 )	61.0 ( 7.3 )	61.1 ( 10.3 )	66.6 ( 8.8 )	66.3 ( 8.9 )	-
Sex: Female, Male
Units: participants
Female	5	3	1	11	9	2	2	3	11	11	7	13	58	26	162
Male	11	3	2	15	9	4	5	4	12	13	18	12	51	29	188
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	1	0	2	0	3
Asian	0	0	0	0	2	0	0	0	0	0	0	1	0	1	4
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Black or African American	0	1	0	0	1	0	0	0	1	2	4	3	5	3	20
White	14	4	3	20	13	4	6	7	21	19	19	21	91	45	287
More than one race	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	2	1	0	6	2	2	1	0	1	2	1	0	11	6	35

End points

Top of page

Reporting group title

Phase1: Isatuximab <=1 mg/kg every 2 weeks (Q2W)

Reporting group description

Reporting group title

Phase 1: Isatuximab 3mg/kg Q2W

Reporting group description

Reporting group title

Phase 1: Isatuximab 5 mg/kg Q2W

Reporting group description

Reporting group title

Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)

Reporting group description

Reporting group title

Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)

Reporting group description

Reporting group title

Phase 1: Isatuximab 10 mg/kg Every Week (QW)

Reporting group description

Reporting group title

Phase 1: Isatuximab 20 mg/kg Q2W

Reporting group description

Reporting group title

Phase 1: Isatuximab 20 mg/kg QW

Reporting group description

Reporting group title

Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W

Reporting group description

Reporting group title

Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W

Reporting group description

Reporting group title

Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W

Reporting group description

Reporting group title

Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W

Reporting group description

Reporting group title

Phase 2 Stage 2: Isatuximab alone

Reporting group description

Participants with relapsed or RRMM, received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator’s decision.

Reporting group title

Phase 2 Stage 2: Isatuximab + Dexamethasone

Reporting group description

Participants with relapsed or RRMM, received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles along with dexamethasone: tablet or as IV infusion (40 mg/day for less than [<] 75 years of age; 20 mg/day for greater than or equal to [>=] 75 years of age) on Days 1, 8, 15 and 22 of each 28 days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator’s decision.

Subject analysis set title

Phase 1: Isatuximab 0.3 mg/kg Q2W

Subject analysis set type

Per protocol

Subject analysis set description

Participants with CD38+ HM, received Isatuximab 0.3 mg/kg, as IV infusion on Day 1of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator’s decision, and/or availability of study drug.

Subject analysis set title

Phase 1: Isatuximab 1 mg/kg Q2W

Subject analysis set type

Per protocol

Subject analysis set description

Participants with CD38+ HM, received Isatuximab 1 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal by participant, investigator’s decision, and/or availability of study drug

Subject analysis set title

Phase 1: Isatuximab

Subject analysis set type

Per protocol

Subject analysis set description

All participants who were enrolled in Phase 1 and received Isatuximab.

Primary: Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)

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End point title

Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) ^[1] ^[2]

End point description

DLTs were assessed using the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 4.03. DLTs were defined as any Grade 3 or higher non-hematological toxicity (with the exception of allergic reaction/hypersensitivity), Grade 4 neutropenia and/or Grade 4 thrombocytopenia lasting longer than 5 days, attributed to isatuximab. Any other toxicity that the Investigator and the Sponsor deemed to be dose-limiting, regardless of the grade, was also considered as DLT. DLT evaluable population included participants who gave their informed consent, received at least 1 dose of isatuximab during Phase 1 and had a DLT assessment at the end of Cycle 2. Data was planned not to be collected and analyzed for the arm: Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma).

End point type

Primary

End point timeframe

Day 1 of Cycle 1 up to Day 14 of Cycle 2

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: As the endpoint was descriptive in nature, no statistical analysis was reported.
[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: Only Phase 1 participants were analyzed in this endpoint.

End point values	Phase1: Isatuximab <=1 mg/kg every 2 weeks (Q2W)	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW
Number of subjects analysed	14	6	3	6	6	6	6
Units: participants	1	1	0	0	0	0	0

No statistical analyses for this end point

Primary: Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

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End point title

Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) ^[3] ^[4]

End point description

Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment. Analysis was performed on AT population which included participants who signed informed consent and received at least 1 dose/even incomplete of isatuximab.

End point type

Primary

End point timeframe

From Baseline up to 30 days after the last dose (maximum duration: 120 weeks )

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: As the endpoint was descriptive in nature, no statistical analysis was reported.
[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: Only Phase 1 participants were analyzed in this endpoint

End point values	Phase1: Isatuximab <=1 mg/kg every 2 weeks (Q2W)	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW
Number of subjects analysed	16	6	3	26	18	6	7	7
Units: participants	16	6	3	26	18	6	7	6

No statistical analyses for this end point

Primary: Phase 2 Stage 1: Percentage of Participants With Overall Response (OR) According to International Myeloma Working Group (IMWG) Uniform Response Criteria

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End point title

Phase 2 Stage 1: Percentage of Participants With Overall Response (OR) According to International Myeloma Working Group (IMWG) Uniform Response Criteria ^[5] ^[6]

End point description

OR defined as participants with stringent complete response (sCR) or complete response (CR) or very good partial response (VGPR) or partial response (PR).Based on IMWG, CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas (STP) and <=5% plasma cells in bone marrow; sCR:CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours;PR: >=50% reduction of serum M-Protein and reduction in urinary M-protein by >=90% or to <200 mg/24 hours;>=50% decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria or >=50% reduction in plasma cells in place of M-protein if present at baseline.Analysis on AT population which included participants who signed informed consent and received at least 1 dose/even incomplete of isatuximab.

End point type

Primary

End point timeframe

From the date of randomization until disease progression or death or data cut-off (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for Stage 1b arm)

Notes
[5] - 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: As the endpoint was descriptive in nature, no statistical analysis was reported.
[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: Only Phase 2 Stage 1 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W	Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W
Number of subjects analysed	23	24	25	25
Units: percentage of participants
number (not applicable)	4.3	29.2	20.0	24.0

No statistical analyses for this end point

Primary: Phase 2 Stage 2: Percentage of Participants With Overall Response According to Updated IMWG Response Criteria

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End point title

Phase 2 Stage 2: Percentage of Participants With Overall Response According to Updated IMWG Response Criteria ^[7] ^[8]

End point description

OR: participants with sCR or CR or VGPR or PR. As per updated IMWG, CR: Negative immunofixation on serum and urine, disappearance of any STP and <=5% plasma cells in bone marrow; normal FLC ratio of 0.26-1.65 in participants with only FLC disease; sCR: CR and normal FLC ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours, >90% decrease in the difference between involved and uninvolved FLC levels; PR: >=50% reduction of serum M-Protein and reduction in urinary M-protein by >=90% or to <200 mg/24 hours; >=50% decrease in the difference between involved and uninvolved FLC levels in place of M-protein criteria or >=50% reduction in plasma cells in place of M-protein if present at baseline. Analysis was performed on AT population.

End point type

Primary

End point timeframe

From the date of randomization to date of death from any cause (maximum duration: 97 weeks)

Notes
[7] - 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: As the endpoint was descriptive in nature, no statistical analysis was reported.
[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: Only Phase 2 Stage 2 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Number of subjects analysed	109	55
Units: percentage of participants
number (not applicable)	23.9	43.6

No statistical analyses for this end point

Secondary: Pharmacokinetic (PK) assessment: Phase 1: Plasma Concentration of Isatuximab observed at the end of an Intravenous infusion (Ceoi)

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End point title

Pharmacokinetic (PK) assessment: Phase 1: Plasma Concentration of Isatuximab observed at the end of an Intravenous infusion (Ceoi) ^[9]

End point description

Ceoi was defined as the plasma concentration of Isatuximab at end of infusion. Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow). Analysis was performed on PK population: participants who gave informed consent, received at least one dose (even if incomplete) of isatuximab, had an assessable PK parameter. Here, "Number of Participants analyzed"=participants evaluable for this outcome measure and “99999” signifies none of the participant were evaluable because at Cycle 3, Day 1, only data for reporting arms “Phase 1: Isatuximab 10mg/kg QW” and “Phase 1: Isatuximab 20mg/kg QW” was planned to be collected and analyzed. Analysis was performed on AT population. Here, n= number of participants with data collected for each category.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 3 Day 1: At the end of infusion

Notes
[9] - 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: Only Phase 1 participants were analyzed in this endpoint.

End point values	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW	Phase 1: Isatuximab 0.3 mg/kg Q2W	Phase 1: Isatuximab 1 mg/kg Q2W
Number of subjects analysed	4	2	15	5	4	3	6	6	3
Units: microgram per milliliter (mcg/mL)
arithmetic mean (standard deviation)
Cycle 1 Day 1 (n= 4, 2, 15, 5, 3, 3, 6, 6, 3)	44.22500 ( 15.30651 )	125.50000 ( 53.03301 )	171.43333 ( 50.18853 )	148.80000 ( 18.48513 )	173.33333 ( 20.64784 )	400.33333 ( 52.51984 )	334.33333 ( 98.28462 )	2.08667 ( 0.65567 )	13.18333 ( 5.74464 )
Cycle 3 Day 1 (n= 0, 0, 0, 0, 4, 0, 6, 0, 0)	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	299.82500 ( 220.83898 )	99999 ( 99999 )	715.33333 ( 188.01241 )	99999 ( 99999 )	99999 ( 99999 )

No statistical analyses for this end point

Secondary: PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab

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End point title

PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab ^[10]

End point description

Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow). Analysis was performed on PK population. Here, "Number of Participants analyzed"=participants evaluable for this outcome measure and “99999” signifies none of the participant were evaluable because at Cycle 3, Day 1, only data for reporting arms “Phase 1: Isatuximab 10mg/kg QW” and “Phase 1: Isatuximab 20mg/kg QW” was planned to be collected and analyzed. 9999=pre-specified not to calculate if n<=2. Here, n= number of participants with data collected for each category.

End point type

Secondary

End point timeframe

For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 168 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 168 hr post-infusion

Notes
[10] - 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: Only Phase 1 participants were analyzed in this endpoint.

End point values	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW	Phase 1: Isatuximab 0.3 mg/kg Q2W	Phase 1: Isatuximab 1 mg/kg Q2W
Number of subjects analysed	4	2	11	5	4	3	6	6	3
Units: mcg/mL
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1 (n= 4, 2, 11, 5, 3, 3, 6, 6, 3)	53.7 ( 28 )	126 ( 9999 )	181 ( 48 )	154 ( 13 )	181 ( 20 )	457 ( 28 )	343 ( 29 )	2.00 ( 31 )	12.4 ( 45 )
Cycle 3 Day 1 1 (n= n= 0, 0, 0, 0, 4, 0, 6, 0, 0)	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	265 ( 67 )	99999 ( 9999 )	712 ( 27 )	99999 ( 99999 )	99999 ( 99999 )

No statistical analyses for this end point

Secondary: PK Assessment: Phase 1: Time to reach maximum plasma concentration observed (tmax) of Isatuximab

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End point title

PK Assessment: Phase 1: Time to reach maximum plasma concentration observed (tmax) of Isatuximab ^[11]

End point description

Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow). Analysis was performed on PK population. Here, "Number of Participants analyzed"=participants evaluable for this outcome measure and “99999” signifies none of the participant were evaluable because at Cycle 3, Day 1, only data for reporting arms “Phase 1: Isatuximab 10mg/kg QW” and “Phase 1: Isatuximab 20mg/kg QW” was planned to be collected and analyzed. Here, n= number of participants with data collected for each category.

End point type

Secondary

End point timeframe

Notes
[11] - 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: Only Phase 1 participants were analyzed in this endpoint.

End point values	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW	Phase 1: Isatuximab 0.3 mg/kg Q2W	Phase 1: Isatuximab 1 mg/kg Q2W
Number of subjects analysed	4	2	11	5	4	3	6	6	3
Units: hours
median (full range (min-max))
Cycle 1 Day 1 (n= 4, 2, 11, 5, 3, 3, 6, 6, 3)	6.99 (4.58 to 8.00)	7.65 (5.13 to 10.17)	4.28 (2.15 to 9.37)	4.92 (2.60 to 30.08)	2.25 (2.20 to 7.50)	5.87 (5.78 to 9.90)	6.83 (3.98 to 10.53)	2.49 (1.42 to 3.43)	4.35 (3.13 to 6.33)
Cycle 3 Day 1 (n= 0, 0, 0, 0, 4, 0, 6, 0, 0)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	4.30 (2.57 to 27.48)	99999 (99999 to 99999)	8.07 (2.87 to 29.03)	99999 (99999 to 99999)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3

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End point title

PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3 ^[12]

End point description

Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow). Analysis was performed on PK population. Here, ‘number analyzed’ = number of participants with available data for each category. Here, n= number of participants with data collected for each category.

End point type

Secondary

End point timeframe

Week 1, 2 and 3

Notes
[12] - 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: Only Phase 1 participants were analyzed in this endpoint.

End point values	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW	Phase 1: Isatuximab 1 mg/kg Q2W
Number of subjects analysed	6	3	18	16	6	6	7	3
Units: mcg/mL
geometric mean (geometric coefficient of variation)
Week 1 (n= 6, 3, 18, 16 6, 6, 7, 3)	1.44 ( 85 )	15.3 ( 90 )	27.6 ( 81 )	44.2 ( 52 )	20.7 ( 63 )	113 ( 37 )	108 ( 33 )	0.00223 ( 86 )
Week 2 (n= 6, 3, 18, 16 6, 6, 7, 3)	0.181 ( 136 )	1.39 ( 116 )	1.97 ( 145 )	8.31 ( 77 )	55.1 ( 63 )	63.9 ( 46 )	194.8 ( 36 )	0.000800 ( 173 )
Week 3 (n= 6, 2, 17, 14, 6, 5, 6, 3)	0.460 ( 121 )	42.7 ( 73 )	4.18 ( 133 )	18.6 ( 71 )	75.9 ( 78 )	91.0 ( 52 )	347.3 ( 36 )	0.000283 ( 145 )

No statistical analyses for this end point

Secondary: PK Assessment: Phase 1: Predicted Cumulative Area under the plasma concentration Curve (AUC) of Isatuximab Over the First Week (0-168 hours) (AUC1W)

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End point title

PK Assessment: Phase 1: Predicted Cumulative Area under the plasma concentration Curve (AUC) of Isatuximab Over the First Week (0-168 hours) (AUC1W) ^[13]

End point description

Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow). Analysis was performed on PK population. Here, "Number of Participants Analyzed" = participants evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Notes
[13] - 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: Only Phase 1 participants were analyzed in this endpoint

End point values	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW	Phase 1: Isatuximab 1 mg/kg Q2W
Number of subjects analysed	6	3	18	16	6	6	7	3
Units: mcg*hour/mL
geometric mean (geometric coefficient of variation)	2624 ( 24 )	7174 ( 54 )	11566 ( 48 )	13480 ( 38 )	12680 ( 35 )	32739 ( 28 )	28405 ( 27 )	222 ( 80 )

No statistical analyses for this end point

Secondary: PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 hours) (AUC2W)

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End point title

PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 hours) (AUC2W) ^[14]

End point description

Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow). Analysis was performed on PK population. Here, "Number of Participants Analyzed" = participants evaluable for this outcome measure

End point type

Secondary

End point timeframe

For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 336 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 336 hr post-infusion

Notes
[14] - 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: Only Phase 1 participants were analyzed in this endpoint.

End point values	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW	Phase 1: Isatuximab 1 mg/kg Q2W
Number of subjects analysed	6	3	18	16	6	6	7	3
Units: mcg*hour/mL
geometric mean (geometric coefficient of variation)	3076 ( 35 )	9546 ( 70 )	14876 ( 64 )	18967 ( 44 )	30187 ( 40 )	48003 ( 31 )	71174 ( 29 )	222 ( 80 )

No statistical analyses for this end point

Secondary: Pharmacodynamic (PD) assessment: Phase 1: Change From Baseline in Serum/Plasma Markers

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End point title

Pharmacodynamic (PD) assessment: Phase 1: Change From Baseline in Serum/Plasma Markers ^[15]

End point description

Serum/plasma markers included: tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1-β), interleukin 6 (IL-6) and interferon-gamma (IFN-Gamma). Due to change in planned analysis, data for high-sensitivity C-reactive protein (hs-CRP) and CD38 was not collected and analyzed. Analysis was performed on all randomized participants who gave their informed consent, had received at least 1 dose (even incomplete) of isatuximab and had an assessable PD parameter. Here, ‘n’ = number of participants with available data for each category. Here, n= number of participants with data collected for each category.

End point type

Secondary

End point timeframe

Cycle 1 Day 1

Notes
[15] - 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: Only Phase 1 participants were analyzed in this endpoint.

End point values	Phase1: Isatuximab <=1 mg/kg every 2 weeks (Q2W)	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW
Number of subjects analysed	16	6	3	26	18	6	7	7
Units: picogram/milliliter (pg/mL)
arithmetic mean (standard deviation)
TNF alpha (n=16, 5, 3, 23, 16, 6, 6, 5)	163.181 ( 253.373 )	179.783 ( 191.455 )	352.974 ( 220.394 )	340.799 ( 341.100 )	503.462 ( 479.813 )	342.664 ( 410.245 )	307.319 ( 398.025 )	412.541 ( 243.169 )
IL-1 Beta (n=15, 4, 3, 21, 16, 6, 6, 5)	64.577 ( 227.399 )	29.741 ( 55.515 )	7.527 ( 8.118 )	299.058 ( 572.260 )	547.770 ( 1454.175 )	327.957 ( 759.305 )	305.914 ( 621.754 )	293.307 ( 612.746 )
IL-6 (n=16, 5, 3, 23, 16, 6, 6, 5)	139.234 ( 212.385 )	261.732 ( 270.119 )	73.899 ( 53.211 )	148.594 ( 175.719 )	173.004 ( 433.297 )	-8.109 ( 45.845 )	274.616 ( 234.752 )	165.295 ( 203.451 )
IFN Gamma (n=15, 3, 3, 23, 16, 6, 6, 5)	477.116 ( 1673.063 )	5.376 ( 9.312 )	25.806 ( 44.698 )	445.772 ( 1043.982 )	568.806 ( 1022.000 )	627.089 ( 1527.647 )	448.387 ( 569.499 )	1487.097 ( 2693.826 )

No statistical analyses for this end point

Secondary: Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response

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End point title

Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response ^[16]

End point description

ADA response was categorized as: treatment induced and treatment boosted response. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period (defined as the time from the first isatuximab administration until end of Phase 1) in participants without preexisting ADA (defined as: ADA that were present in samples drawn before treatment), including participants without pre-treatment (before treatment) samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment (before treatment) and post-treatment. Analysis was performed on ADA evaluable population which included all treated participants with at least one ADA assessment with a reportable result during the ADA on-study observation period.

End point type

Secondary

End point timeframe

Up to 120 weeks

Notes
[16] - 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: Only Phase 1 participants were analyzed in this endpoint.

End point values	Phase1: Isatuximab <=1 mg/kg every 2 weeks (Q2W)	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW
Number of subjects analysed	16	6	3	26	18	6	6	7
Units: participants
Treatment-induced ADA	2	0	0	1	1	1	1	1
Treatment boosted ADA	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Clinical assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) criteria

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End point title

Clinical assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) criteria ^[17]

End point description

OR:Participants with CR or PR as best overall response (BOR). Clinical benefit: participants with minimal response (MR) or better as BOR.BOR: best sequential response from start of treatment through the entire study excluding any time point following start of other treatment.CR: negative immunofixation on serum and urine, disappearance of any STP,<5% plasma cells in bone marrow aspirates, no increase in size or number of lytic bone lesions.PR: >=50% reduction of serum M-protein, reduction in 24 h urinary M-protein by >=90% or <200mg,>=50% reduction in size/number of STP, no increase in size or number of lytic bone lesions. MR: 25 to 49% reduction in serum M-protein, 50-89% reduction in 24h urine M-protein, 25-49% reduction in size of STP, no increase in size or number of lytic bone lesions. Analysis was performed on AT population. Here, 'number of participants analyzed' = participants evaluable for this outcome measure.

End point type

Secondary

End point timeframe

From the date of randomization to the date of first documentation of progression or death (due to any cause) (maximum duration: 120 weeks)

Notes
[17] - 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: Only Phase 1 participants were analyzed in this endpoint.

End point values	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW	Phase 1: Isatuximab 1 mg/kg Q2W
Number of subjects analysed	5	3	25	18	6	7	7	3
Units: percentage of participants
number (not applicable)
OR	0	33.3	28.0	16.7	33.3	14.3	28.6	33.3
Clinical benefit	20.0	33.3	28.0	27.8	33.3	28.6	42.9	33.3

No statistical analyses for this end point

Secondary: Clinical assessment: Phase 1: Duration of response (DOR)

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End point title

Clinical assessment: Phase 1: Duration of response (DOR) ^[18]

End point description

DOR: time from first response (PR or better) to first documented tumor progression/death.Progression (EBMT):>25% increase in serum monoclonal paraprotein level also absolute increase of >=5 g/l:>25% increase in 24h urinary light chain excretion also absolute increase of >=200 mg/24 h:>25% increase in plasma cells in a bone marrow aspirate/on trephine biopsy also absolute increase of >=10%;definite increase in size of existing bone lesions/STP; development of new bone lesions/STP or hypercalcemia (corrected serum calcium >11·5 mg/dl) not attributable to any other cause.PR:>=50% reduction of serum M-protein, reduction in 24h urinary M-protein by >=90% or <200mg,>=50% reduction in size/number of STP, no increase in size/number of lytic bone lesions. Analysis only on subset of participants who had response in Phase 1; not for reporting group with no response.22222=standard deviation cannot be calculated for single participant.

End point type

Secondary

End point timeframe

From the date of first response to the date of first documentation of progression or death (due to any cause) (maximum duration: 120 weeks)

Notes
[18] - 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: Only Phase 1 participants were analyzed in this endpoint.

End point values	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW	Phase 1: Isatuximab 1 mg/kg Q2W
Number of subjects analysed	1	7	3	2	1	2	1
Units: months
arithmetic mean (standard deviation)	7.16 ( 22222 )	5.76 ( 4.62 )	10.70 ( 11.25 )	14.31 ( 7.50 )	3.94 ( 22222 )	8.82 ( 7.83 )	20.21 ( 22222 )

No statistical analyses for this end point

Secondary: Clinical assessment: Phase 1: Time to First Response (TTR)

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End point title

Clinical assessment: Phase 1: Time to First Response (TTR) ^[19]

End point description

TTR was defined as the time from first dose of isatuximab to first response (PR or better). PR: >=50% reduction of serum M-protein, reduction in 24 h urinary M-protein by >=90% or <200mg, >=50% reduction in size/number of STP, no increase in size or number of lytic bone lesions. Analysis was performed only on subset of participants who had response in Phase 1 and not for the reporting group with no response. 22222=standard deviation cannot be calculated for a single participant.

End point type

Secondary

End point timeframe

From the date of first dose administration to the date of first response or death (due to any cause) (maximum duration: 120 weeks)

Notes
[19] - 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: Only Phase 1 participants were analyzed in this endpoint.

End point values	Phase 1: Isatuximab 5 mg/kg Q2W	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase 1: Isatuximab 10 mg/kg Every Week (QW)	Phase 1: Isatuximab 20 mg/kg Q2W	Phase 1: Isatuximab 20 mg/kg QW	Phase 1: Isatuximab 1 mg/kg Q2W
Number of subjects analysed	1	7	3	2	1	2	1
Units: months
arithmetic mean (standard deviation)	6.41 ( 22222 )	2.52 ( 3.77 )	1.96 ( 1.72 )	1.38 ( 0.65 )	1.18 ( 22222 )	1.46 ( 0.77 )	0.95 ( 22222 )

No statistical analyses for this end point

Secondary: Clinical assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Karnofsky performance status)-Shift From Baseline Value to Best Value During Treatment

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End point title

Clinical assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Karnofsky performance status)-Shift From Baseline Value to Best Value During Treatment

End point description

ECOG performance status was measured on a 4 point scale to assess participant's performance status. 0=Normal, fully functional; 1=Fatigue without significant decrease in daily activity; 2=Fatigue with significant impairment of daily activities or bed rest <50% of waking hours; 3=Bed rest/sitting >50% of waking hours; 4=Bedridden or unable to care for self, where lower score indicated good performance status. Number of participants with Baseline ECOG PS score and corresponding changes to the best values (categorized as: Baseline ECOG 1, During Treatment ECOG 0; Baseline ECOG 2, During Treatment ECOG 0; Baseline ECOG 2, During Treatment ECOG 1) are reported. Analysis was performed on AT population. Data for this outcome measure was planned to be collected and analyzed for a combined arm of overall Phase 1 AT population.

End point type

Secondary

End point timeframe

At baseline, during treatment (Day 1 up to 120 weeks)

End point values	Phase 1: Isatuximab
Number of subjects analysed	89
Units: participants
Baseline ECOG 1, During Treatment ECOG 0	11
Baseline ECOG 2, During Treatment ECOG 0	2
Baseline ECOG 2, During Treatment ECOG 1	11

No statistical analyses for this end point

Secondary: Clinical assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky performance status)-Shift From Baseline Value to Worst Value During Treatment

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End point title

Clinical assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky performance status)-Shift From Baseline Value to Worst Value During Treatment

End point description

ECOG performance status was measured on a 4 point scale to assess participant's performance status. 0=Normal, fully functional; 1=Fatigue without significant decrease in daily activity; 2=Fatigue with significant impairment of daily activities or bed rest <50% of waking hours; 3=Bed rest/sitting>50% of waking hours; 4=Bedridden or unable to care for self, where higher score indicated worst performance status.Number of participants with Baseline ECOG PS score and corresponding changes to the worst values (categorized as: Baseline ECOG 0, During Treatment ECOG 1; Baseline ECOG 2, During Treatment ECOG 1; Baseline ECOG 0, During Treatment ECOG 2; Baseline ECOG 1, During Treatment ECOG 2; Baseline ECOG 0, During Treatment ECOG 3; Baseline ECOG 1, During Treatment ECOG 3; Baseline ECOG 2, During Treatment ECOG 3) are reported. Analysis was performed on AT population. Data for this outcome measure was planned to be collected and analyzed for a combined arm of overall Phase 1 AT population.

End point type

Secondary

End point timeframe

At baseline, during treatment (up to 120 weeks)

End point values	Phase 1: Isatuximab
Number of subjects analysed	89
Units: participants
Baseline ECOG 0, During Treatment ECOG 1	8
Baseline ECOG 2, During Treatment ECOG 1	1
Baseline ECOG 0, During Treatment ECOG 2	3
Baseline ECOG 1, During Treatment ECOG 2	20
Baseline ECOG 0, During Treatment ECOG 3	1
Baseline ECOG 1, During Treatment ECOG 3	2
Baseline ECOG 2, During Treatment ECOG 3	1

No statistical analyses for this end point

Secondary: Phase 2 Stage 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

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End point title

Phase 2 Stage 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) ^[20]

End point description

Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment. Analysis was performed on AT population which included participants who signed informed consent & received at least 1 dose/even incomplete of isatuximab.

End point type

Secondary

End point timeframe

From Baseline up to 30 days after the last dose (maximum duration: 414 weeks for Stage 1a and 92 weeks for Stage 1b)

Notes
[20] - 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: Only Phase 2 Stage 1 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W	Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W
Number of subjects analysed	23	24	25	25
Units: participants	22	24	25	25

No statistical analyses for this end point

Secondary: Phase 2 Stage 1: Duration of Response

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End point title

Phase 2 Stage 1: Duration of Response ^[21]

End point description

DOR:Time from date of 1st IAC determined response (>= PR) that was subsequently confirmed, to date of first IAC determined PD/death, whichever happened earlier. updated IMWG criteria- PR:>=50% decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria or a >=50% reduction in plasma cells in place of M-protein if baseline was >=30%.If present at baseline a >=50% reduction in size of STP; PD: Increase of 25% from lowest response value in any of following: Serum M-protein >=0.5 g/dL absolute increase and/or urine M-protein >=200 mg/24 hours absolute increase and/or >10 mg/dL absolute increase in difference between involved and uninvolved FLC levels>=10% bone marrow plasma cells (PC), development of new or increase in size of bone lesions/STP, development of hypercalcemia. Analysis was only on subset of population who had response in Phase 2 stage 1.22222=Standard deviation cannot be calculated for single participant.

End point type

Secondary

End point timeframe

From the date of first response until disease progression or death or data cut-off (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)

Notes
[21] - 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: Only Phase 2 Stage 1 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W	Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W
Number of subjects analysed	1	7	5	6
Units: months
arithmetic mean (standard deviation)	1.91 ( 22222 )	11.17 ( 5.77 )	7.31 ( 3.65 )	8.11 ( 2.33 )

No statistical analyses for this end point

Secondary: Phase 2 Stage 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

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End point title

Phase 2 Stage 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) ^[22]

End point description

AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment. Analysis was performed on AT population which included participants who signed informed consent & received at least 1 dose/even incomplete of isatuximab.

End point type

Secondary

End point timeframe

From Baseline up to 30 days after the last dose (maximum duration: 301 weeks)

Notes
[22] - 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: Only Phase 2 Stage 2 participants were analyzed in this endpoint

End point values	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Number of subjects analysed	109	55
Units: participants	101	51

No statistical analyses for this end point

Secondary: Phase 2 Stage 2: Percentage of Participants With Clinical Benefit

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End point title

Phase 2 Stage 2: Percentage of Participants With Clinical Benefit ^[23]

End point description

Clinical benefit:participants with sCR, CR, VGPR, PR or MR, per IMWG criteria, determined by IAC. CR:negative immunofixation on serum & urine, disappearance of any STP,<5% plasma cells in bone marrow aspirates,normal FLC ratio(0.26-1.65) in participants with only FLC disease.sCR:CR+normal FLC ratio, absence of clonal cells in bone marrow biopsy.VGPR:serum & urine M-component detectable by immunofixation, not on electrophoresis/,>=90% reduction in serum M-component plus urine M-component level <100mg/24h/,>=90% decrease in difference between involved and uninvolved FLC levels; PR:>=50% reduction of serum M-protein, reduction in 24h urinary M-protein by >=90%/<200mg/24h,>50% decrease in difference between involved and uninvolved FLC in place of M-protein criteria, >=50% reduction in size/number of STP. MR:>=25 but <49% reduction in serum M-protein,reduction in 24h urine M-protein by 50-89%, 25-49% reduction in size of STP. Analysis was on AT population.

End point type

Secondary

End point timeframe

From the date of randomization to the date of first documentation of progression or death (maximum duration: 97 weeks )

Notes
[23] - 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: Only Phase 2 Stage 2 participants were analyzed in this endpoint

End point values	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Number of subjects analysed	109	55
Units: percentage of participants
number (not applicable)	43.1	54.5

No statistical analyses for this end point

Secondary: Phase 2 Stage 1: Percentage of Participants With Clinical Benefit

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End point title

Phase 2 Stage 1: Percentage of Participants With Clinical Benefit ^[24]

End point description

Clinical benefit:participants with sCR, CR, VGPR, PR or MR as per IMWG criteria by IAC.CR: negative immunofixation on serum & urine, disappearance of any STP, <5% PCs in bone marrow aspirates. sCR: CR + normal FLC ratio (0.26-1.65), absence of clonal cells in bone marrow biopsy. VGPR: serum & urine M-component detectable by immunofixation, not on electrophoresis/,>=90% reduction in serum M-component plus urine M-component level <100mg/24hours; PR: >=50% reduction of serum M-Protein and reduction in urinary M-protein by>=90% or to <200 mg/24 hours,>=50% decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria or >=50% reduction in plasma cells in place of M-protein if baseline >=30%. If present at baseline,>=50% size reduction in STP. MR:>=25 but <49% reduction in serum M-protein,reduction in 24h urine M-protein by 50-89%, 25-49% size reduction in STP. Analysis was on AT population.

End point type

Secondary

End point timeframe

From the date of randomization to the date of first documentation of progression or death (maximum duration: 77 weeks for Stage 1 for Stage 1a arms and 53 weeks for stage 1b arm)

Notes
[24] - 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: Only Phase 2 Stage 1 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W	Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W
Number of subjects analysed	23	24	25	25
Units: percentage of participants
number (not applicable)	4.3	41.7	32.0	36.0

No statistical analyses for this end point

Secondary: Phase 2 Stage 2: Duration of Response

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End point title

Phase 2 Stage 2: Duration of Response ^[25]

End point description

DOR: Time from date of 1st IAC determined response (>= PR) subsequently confirmed, to date of 1st IAC determined PD or death, whichever happened earlier. As per updated IMWG criteria-PR: >=50% reduction of serum M-Protein and reduction in urinary M-protein by >=90% or to <200 mg/24 hours.>=50% decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria or ≥50% reduction in plasma cells in place of M-protein if baseline >=30%. If present at baseline >=50% reduction in size of STP; PD: Increase of >25% from lowest response value in any 1 of following: Serum M-component (absolute increase >0.5 g/dL)4 and/or Urine M-component (absolute increase 200 mg/24 h) and/or >10 mg/dL absolute increase in difference between involved and uninvolved FLC levels,>=10% bone marrow plasma cell,development of hypercalcemia attributed solely to PC proliferative disorder. Analysis was only on subset of population who had response in Phase 2 stage 2.

End point type

Secondary

End point timeframe

From the date of first response until disease progression or death or data cut-off (maximum duration: 97 weeks)

Notes
[25] - 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: Only Phase 2 Stage 2 participants were analyzed in this endpoint

End point values	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Number of subjects analysed	26	24
Units: months
arithmetic mean (standard deviation)	8.6 ( 5.2 )	10.9 ( 4.6 )

No statistical analyses for this end point

Secondary: Phase 2 Stage 1: Progression free survival (PFS)

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End point title

Phase 2 Stage 1: Progression free survival (PFS) ^[26]

End point description

PFS:Time interval from date of first isatuximab administration to date of first IAC-confirmed disease progression (PD) or date of death due to any cause, whichever came first. As per IMWG criteria, PD: Increase of > 25% from lowest response value in any 1 or more of following: Serum M-component and/or (absolute increase> 0.5 g/dL),Urine M-component and/or (absolute increase> 200 mg/24 h), > 10mg/dL decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria,>10% absolute percentage of bone marrow plasma cell, definite development of new bone lesions or STP or definite increase in the size of existing bone lesions or STP, development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) attributed solely to PC proliferative disorder. Analysis was performed by Kaplan-Meier method. Analysis was performed on AT population. 55555=Upper limit of confidence interval was not estimable due to less number of participants with event.

End point type

Secondary

End point timeframe

From the date of the first dose administration until progression or death, whichever occurred first (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)

Notes
[26] - 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: Only Phase 2 Stage 1 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W	Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W
Number of subjects analysed	23	24	25	25
Units: months
median (confidence interval 95%)	2.1 (1.02 to 5.49)	9.6 (2.23 to 55555)	4.4 (1.84 to 5.82)	3.6 (1.91 to 9.20)

No statistical analyses for this end point

Secondary: Phase 2 Stage 2: Overall survival

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End point title

Phase 2 Stage 2: Overall survival ^[27]

End point description

OS was defined as the time interval from the date of first Isatuximab administration to death from any cause. Analysis was performed by Kaplan-Meier method. Analysis was performed on AT population. 55555=Not estimable, due to less number of participants with event.

End point type

Secondary

End point timeframe

From the date of randomization to date of death from any cause (maximum duration: 97 weeks)

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only Phase 2 Stage 2 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Number of subjects analysed	109	55
Units: months
median (confidence interval 95%)	18.92 (13.602 to 23.064)	17.25 (15.409 to 55555)

No statistical analyses for this end point

Secondary: Phase 2 Stage 1: Overall survival (OS)

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End point title

Phase 2 Stage 1: Overall survival (OS) ^[28]

End point description

OS was defined as the time interval from the date of first Isatuximab administration to death from any cause. Analysis was performed by Kaplan-Meier method. Analysis was performed on AT population. 55555= Not estimable, due to less number of participants with event.

End point type

Secondary

End point timeframe

From the date of randomization to date of death from any cause (maximum duration 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)

Notes
[28] - 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: Only Phase 2 Stage 1 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W	Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W
Number of subjects analysed	23	24	25	25
Units: months
median (confidence interval 95%)	15.277 (4.7310 to 55555)	18.628 (7.7536 to 20.1068)	55555 (8.4435 to 55555)	55555 (8.3450 to 55555)

No statistical analyses for this end point

Secondary: Phase 2 Stage 2: Progression free survival

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End point title

Phase 2 Stage 2: Progression free survival ^[29]

End point description

PFS was defined as the time interval from the date of first isatuximab administration to the date of the first IAC-confirmed disease progression or the date of death due to any cause, whichever came first. As per IMWG criteria, PD: Increase of >25% from lowest response value in any one of the following: Serum M-component (the absolute increase must be >0.5 g/dL)4 and/or Urine M-component (the absolute increase must be >200 mg/24 h) and/or >10 mg/dL decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria, ≥10% bone marrow plasma cell, development of hypercalcemia (corrected serum calcium >11.5 mg/dL) attributed solely to the plasma cell proliferative disorder. Analysis was performed by Kaplan-Meier method. Analysis was performed on AT population.

End point type

Secondary

End point timeframe

From the date of the first dose administration until progression or death, whichever occurred first (maximum duration: 97 weeks)

Notes
[29] - 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: Only Phase 2 Stage 2 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Number of subjects analysed	109	55
Units: months
median (confidence interval 95%)	4.86 (3.877 to 7.688)	10.15 (4.862 to 17.347)

No statistical analyses for this end point

Secondary: Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status

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End point title

Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status ^[30]

End point description

EORTC-QLQ-C30:Cancer-specific instrument with 30 questions for evaluation of new chemotherapy;provides an assessment of participant reported outcome dimensions.1st 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social),3 symptom scales (fatigue,nausea/vomiting,pain);other single items.For each item,high score=high level of problem.Last 2 questions were participant’s assessment of overall health+quality of life (QoL),coded on 7-point scale (1=very poor to 7=excellent).It observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales,3 symptom scales and other single items (scoring of questions 1 to 28).Answers were converted into grading scale, values between 0 and 100.High score:favorable outcome with best QoL. Analysis:AT population.Only those participants with data available for each specified category are reported.

End point type

Secondary

End point timeframe

Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10 and End of Treatment (EOT: anytime up to 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)

Notes
[30] - 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: Only Phase 2 Stage 1 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W	Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W
Number of subjects analysed	22	21	24	22
Units: score on a scale
arithmetic mean (standard deviation)
Cycle 2 day 1 (n=14, 15, 19, 18)	-8.33 ( 20.15 )	2.22 ( 16.51 )	-3.95 ( 20.67 )	0.00 ( 15.39 )
Cycle 3 day 1 (n=7, 11, 14, 12)	0.00 ( 19.25 )	-0.76 ( 16.44 )	6.55 ( 19.66 )	-2.08 ( 15.54 )
Cycle 4 day 1 (n=4, 11, 11, 9)	0.00 ( 24.53 )	-5.30 ( 21.50 )	6.06 ( 21.11 )	7.41 ( 8.78 )
Cycle 5 day 1 (n=4, 12, 9, 5)	0.00 ( 24.53 )	0.69 ( 15.27 )	6.48 ( 21.15 )	5.00 ( 4.56 )
Cycle 6 day 1 (n=4, 9, 7, 4)	12.50 ( 14.43 )	-10.19 ( 25.27 )	5.95 ( 13.36 )	10.42 ( 7.98 )
Cycle 7 day 1 (n=2, 7, 4, 5)	12.50 ( 5.89 )	-3.57 ( 15.85 )	8.33 ( 11.79 )	6.67 ( 6.97 )
Cycle 8 day 1 (n=2, 6, 4, 4)	0.00 ( 35.36 )	-11.11 ( 18.76 )	4.17 ( 15.96 )	6.25 ( 10.49 )
Cycle 9 day 1 (n=2, 5, 4, 4)	-8.33 ( 11.79 )	-10.00 ( 19.90 )	4.17 ( 14.43 )	6.25 ( 10.49 )
Cycle 10 day 1 (n=2, 3, 4, 5)	-8.33 ( 35.36 )	-16.67 ( 22.05 )	8.33 ( 11.79 )	3.33 ( 7.45 )
End of treatment (n=5, 5, 3, 2)	3.33 ( 33.64 )	-11.67 ( 13.94 )	-11.11 ( 20.97 )	-12.50 ( 5.89 )

No statistical analyses for this end point

Secondary: Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score

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End point title

Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score ^[31]

End point description

EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with MM. It has 4 subscales: body image, future perspective), and 2 symptoms scales (disease symptoms and side-effects of treatment). Disease symptoms subscale used 4-point scale ranged from 1= 'Not at All' to 4= 'Very Much'. Scores were averaged, and transformed to 0 -100 scale, where higher scores = more symptoms and lower health-related quality of life (HRQL) and lower score = less symptoms and more HRQL. Analysis was performed on AT population. Here, "Number of Participants Analyzed" = participants evaluable for this outcome measure and 'n' = number of participants with data collected for each category.

End point type

Secondary

End point timeframe

Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10 and EOT (anytime up to 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)

Notes
[31] - 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: Only Phase 2 Stage 1 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W	Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W
Number of subjects analysed	22	21	23	22
Units: score on a scale
arithmetic mean (standard deviation)
Cycle 2 day 1 (n=14, 13, 18, 17)	5.56 ( 18.36 )	-3.42 ( 11.24 )	0.93 ( 13.91 )	2.61 ( 18.75 )
Cycle 3 day 1 (n=7, 11, 13, 11)	7.94 ( 11.94 )	-5.05 ( 14.15 )	-5.98 ( 16.89 )	-1.52 ( 13.17 )
Cycle 4 day 1 (n=4, 10, 10, 9)	8.33 ( 13.22 )	-3.89 ( 16.98 )	-10.00 ( 16.93 )	0.62 ( 30.10 )
Cycle 5 day 1 (n=4, 11, 8, 5)	-6.94 ( 10.52 )	0.51 ( 19.95 )	-9.03 ( 17.04 )	-6.67 ( 17.74 )
Cycle 6 day 1 (n=4, 9, 7, 4)	8.33 ( 7.17 )	1.23 ( 23.53 )	-15.08 ( 20.96 )	-6.94 ( 10.52 )
Cycle 7 day 1 (n=2, 6, 4, 5)	2.78 ( 3.93 )	-3.70 ( 22.95 )	-18.06 ( 21.93 )	-11.11 ( 11.79 )
Cycle 8 day 1 (n=2, 6, 4, 4)	-5.56 ( 7.86 )	-2.78 ( 23.50 )	-15.28 ( 23.30 )	-4.17 ( 5.32 )
Cycle 9 day 1 (n=2, 5, 4, 4)	5.56 ( 7.86 )	-10.00 ( 10.69 )	-16.67 ( 29.75 )	-6.94 ( 12.32 )
Cycle 10 day 1 (n=2, 3, 4, 5)	0.00 ( 0.00 )	0.00 ( 19.25 )	-15.28 ( 30.56 )	-6.67 ( 17.30 )
End of treatment (n=4, 5, 3, 2)	-9.72 ( 19.44 )	7.78 ( 24.41 )	24.07 ( 22.45 )	25.00 ( 35.36 )

No statistical analyses for this end point

Secondary: Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores

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End point title

Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores ^[32]

End point description

EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. Analysis was performed on AT population. Here, "Number of Participants Analyzed" = participants evaluable for this outcome measure and 'n' = number of participants with available data for each category. 22222=Standard deviation cannot be calculated for a single participant. 99999=no evaluable participants

End point type

Secondary

End point timeframe

Baseline, Day 1 of Cycles 4, 7, 10, 13, 16, 19, and EOT (anytime up to 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)

Notes
[32] - 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: Only Phase 2 Stage 1 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W	Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W
Number of subjects analysed	22	21	22	22
Units: score on a scale
arithmetic mean (standard deviation)
Cycle 4 day 1 (n=4, 9, 9, 9)	-5.75 ( 18.55 )	2.00 ( 16.88 )	-4.78 ( 15.71 )	4.89 ( 16.02 )
Cycle 7 day 1 (n=2, 6, 3, 5)	-2.50 ( 0.71 )	-6.00 ( 27.39 )	9.00 ( 18.25 )	1.00 ( 7.94 )
Cycle 10 day 1 (n=2, 3, 3, 5)	0.50 ( 2.12 )	-10.33 ( 9.29 )	10.33 ( 24.38 )	-2.60 ( 8.11 )
Cycle 13 day 1 (n=2, 3, 1, 1)	14.00 ( 19.80 )	-5.00 ( 4.00 )	-9.00 ( 22222 )	-5.00 ( 22222 )
Cycle 16 day 1 (n=2, 3, 0, 0)	5.00 ( 5.66 )	0.67 ( 23.71 )	99999 ( 99999 )	99999 ( 99999 )
Cycle 19 day 1 (n=0, 2, 0, 0)	99999 ( 99999 )	-5.50 ( 4.95 )	99999 ( 99999 )	99999 ( 99999 )
End of treatment (n=4, 5, 3, 2)	-18.50 ( 16.98 )	-11.60 ( 11.37 )	-10.00 ( 9.54 )	-9.00 ( 0.00 )

No statistical analyses for this end point

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: Area under the plasma concentration versus time curve of Isatuximab over 1 week interval

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End point title

Pharmacokinetic assessment: Phase 2 Stage 2: Area under the plasma concentration versus time curve of Isatuximab over 1 week interval ^[33]

End point description

Analysis was performed on PK population which included participants who gave informed consent, received at least one dose (even if incomplete) of isatuximab, had an assessable PK parameter.

End point type

Secondary

End point timeframe

Pre-dose, at the end of infusion, 1 hour and 168 hours post dose on Day 1 of Cycle 1

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only Phase 2 Stage 2 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Number of subjects analysed	102	52
Units: mcg*hour/mL
geometric mean (geometric coefficient of variation)	37096 ( 80 )	35423 ( 88 )

No statistical analyses for this end point

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: Area under the plasma concentration versus time curve of Isatuximab over 2 weeks interval

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End point title

Pharmacokinetic assessment: Phase 2 Stage 2: Area under the plasma concentration versus time curve of Isatuximab over 2 weeks interval ^[34]

End point description

Analysis was performed on PK population.

End point type

Secondary

End point timeframe

Cycle 1, Day 1: pre-dose, at the end of infusion, 168 and 336 hours post-infusion

Notes
[34] - 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: Only Phase 2 Stage 2 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Number of subjects analysed	102	52
Units: mcg*hour/mL
geometric mean (geometric coefficient of variation)	91271 ( 78 )	86761 ( 77 )

No statistical analyses for this end point

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: Area under the plasma concentration versus time curve of Isatuximab over 4 weeks interval

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End point title

Pharmacokinetic assessment: Phase 2 Stage 2: Area under the plasma concentration versus time curve of Isatuximab over 4 weeks interval ^[35]

End point description

Analysis was performed on PK population.

End point type

Secondary

End point timeframe

Cycle 1, Day 1: pre-dose, at the end of infusion, 168, 336, and 672 hours post-infusion

Notes
[35] - 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: Only Phase 2 Stage 2 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Number of subjects analysed	102	52
Units: mcg*hour/mL
geometric mean (geometric coefficient of variation)	236360 ( 72 )	226372 ( 66 )

No statistical analyses for this end point

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: Accumulation ratio of Isatuximab based on Ctrough

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End point title

Pharmacokinetic assessment: Phase 2 Stage 2: Accumulation ratio of Isatuximab based on Ctrough ^[36]

End point description

Ctrough is the plasma concentration observed before treatment administration. For 1st category, the accumulation ratio was calculated by dividing Ctrough value of Cycle 2 Day 1 by Cycle 1 Day 8 and for second category, accumulation ratio was calculated by dividing Ctrough value of Cycle 4 Day 1 by Cycle 1 Day 8. Analysis was performed on PK population. Here, ‘number of participants analyzed’ = participants evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Cycle 2, Day 1; Cycle 1, Day 8; Cycle 4, Day 1

Notes
[36] - 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: Only Phase 2 Stage 2 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Number of subjects analysed	95	48
Units: ratio
arithmetic mean (standard deviation)
Cycle 2 Day 1/Cycle 1 Day 8	521.38338 ( 4891.63390 )	3.24370 ( 1.73860 )
Cycle 4 Day 1/Cycle 1 Day 8	3.58378 ( 2.77398 )	3.95950 ( 3.19310 )

No statistical analyses for this end point

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: plasma concentration of Isatuximab before treatment administration (Ctrough)

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End point title

Pharmacokinetic assessment: Phase 2 Stage 2: plasma concentration of Isatuximab before treatment administration (Ctrough) ^[37]

End point description

Analysis was performed on PK population.

End point type

Secondary

End point timeframe

At Days 7, 14, 28

Notes
[37] - 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: Only Phase 2 Stage 2 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Number of subjects analysed	102	52
Units: mcg/mL
geometric mean (geometric coefficient of variation)
Day 7	137 ( 75 )	128 ( 54 )
Day 14	230 ( 70 )	214 ( 57 )
Day 28	360 ( 63 )	305 ( 66 )

No statistical analyses for this end point

Secondary: Immunogenicity assessment: Phase 2 Stage 2: Number of participants with anti-drug antibodies to Isatuximab

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End point title

Immunogenicity assessment: Phase 2 Stage 2: Number of participants with anti-drug antibodies to Isatuximab ^[38]

End point description

ADA response was categorized as: treatment induced and treatment boosted response. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period (defined as the time from the first isatuximab administration until end of Phase 2 Stage 2) in participants without preexisting ADA (defined as: ADA that were present in samples drawn before treatment), including participants without pre-treatment (before treatment) samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment (before treatment) and post-treatment. Analysis was performed on ADA evaluable population which included all treated participants with at least one ADA assessment with a reportable result during the ADA on-study observation period.

End point type

Secondary

End point timeframe

Up to 97 weeks

Notes
[38] - 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: Only Phase 2 Stage 2 participants were analyzed in this endpoint.

End point values	Phase 2 Stage 2: Isatuximab alone	Phase 2 Stage 2: Isatuximab + Dexamethasone
Number of subjects analysed	107	53
Units: participants
Treatment induced ADA	1	0
Treatment boosted ADA	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

All AEs=from signing of informed consent up to 30 days from last administration of IP(maximum exposure:up to 120 weeks-Phase 1, 414 weeks-Phase 2 Stage 1a,92 weeks-Phase 2 Stage 1b, 301 weeks-Phase 2 Stage 2).Deaths=for entire study duration, 683 weeks

Adverse event reporting additional description

Reported AEs were TEAEs which was defined as an AE that developed or worsened during the ‘on treatment period’ (time from the first dose of any study treatment up to 30 days after the last administration of the study treatment). Analysis was performed on AT population. Phase 1 MedDRA version was 19.1. Phase 2 MedDRA version was 26.0.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

Phase 1: Isatuximab 10mg/kg QW

Reporting group description

Reporting group title

Phase 1: Isatuximab 20mg/kg Q2W

Reporting group description

Reporting group title

Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)

Reporting group description

Reporting group title

Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)

Reporting group description

Participants with CD38+ HM along with participants with standard risk multiple myeloma were included in this arm and, received Isatuximab 10 mg/kg, as IV infusion on Day 1 of each 14-daytreatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug.

Reporting group title

Phase 1: Isatuximab 5mg/kg Q2W

Reporting group description

Reporting group title

Phase 1: Isatuximab 3mg/kg Q2W

Reporting group description

Reporting group title

Phase 1: Isatuximab <=1mg/kg Q2W

Reporting group description

Participants with CD38+ HM, received Isatuximab at any one of the dose <=1 mg/kg (i.e. either 0.0001 mg/kg or 0.001 mg/kg or 0.01 mg/kg or 0.03 mg/kg, or 0.1 mg/kg or 0.3 mg/kg or 1 mg/kg) as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal by participant, investigator's decision, and/or availability of study drug.

Reporting group title

Phase 1: Isatuximab 20mg/kg QW

Reporting group description

Reporting group title

Phase 2 Stage 2: Isatuximab Alone

Reporting group description

Participants with relapsed or relapsed/refractory multiple myeloma (RRMM), received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator's decision.

Reporting group title

Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W

Reporting group description

Reporting group title

Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W

Reporting group description

Reporting group title

Phase 2 Stage 1a: Isatuximab 3mg/kg Q2W

Reporting group description

Reporting group title

Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W

Reporting group description

Reporting group title

Phase 2 Stage 2: Isatuximab + Dexamethasone

Reporting group description

Participants with relapsed or RRMM, received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles along with dexamethasone: tablet or as IV infusion (40 mg/day for <75 years of age; 20 mg/day for >=75 years of age) on Days 1, 8, 15 and 22 of each 28 days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator’s decision.

Phase 1: Isatuximab 10mg/kg QW

Phase 1: Isatuximab 20mg/kg Q2W

Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)

Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)

Phase 1: Isatuximab 5mg/kg Q2W

Phase 1: Isatuximab 3mg/kg Q2W

Phase 1: Isatuximab <=1mg/kg Q2W

Phase 1: Isatuximab 20mg/kg QW

Phase 2 Stage 2: Isatuximab Alone

Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W

Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W

Phase 2 Stage 1a: Isatuximab 3mg/kg Q2W

Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W

Phase 2 Stage 2: Isatuximab + Dexamethasone

Total subjects affected by serious adverse events

subjects affected / exposed

3 / 6 (50.00%)

3 / 7 (42.86%)

10 / 18 (55.56%)

10 / 26 (38.46%)

1 / 3 (33.33%)

3 / 6 (50.00%)

3 / 16 (18.75%)

3 / 7 (42.86%)

52 / 109 (47.71%)

10 / 25 (40.00%)

11 / 24 (45.83%)

13 / 23 (56.52%)

9 / 25 (36.00%)

27 / 55 (49.09%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Basal Cell Carcinoma

subjects affected / exposed

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colon Cancer

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Myelodysplastic Syndrome

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 16 (6.25%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant Melanoma

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Plasma Cell Leukaemia

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Prostate Cancer

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 18 (5.56%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Squamous Cell Carcinoma Of The Oral Cavity

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Aortic Aneurysm

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Extrinsic Iliac Vein Compression

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypertensive Crisis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

1 / 26 (3.85%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Chills

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Asthenia

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Disease Progression

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 16 (6.25%)

0 / 7 (0.00%)

7 / 109 (6.42%)

1 / 25 (4.00%)

0 / 24 (0.00%)

4 / 23 (17.39%)

1 / 25 (4.00%)

2 / 55 (3.64%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 7

0 / 1

0 / 0

0 / 4

0 / 1

0 / 2

deaths causally related to treatment / all

0 / 0

6 / 7

1 / 1

0 / 0

4 / 4

0 / 1

2 / 2

Fatigue

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Feeling Cold

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Hyperpyrexia

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General Physical Health Deterioration

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Non-Cardiac Chest Pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

1 / 26 (3.85%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malaise

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

1 / 26 (3.85%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Physical Deconditioning

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

1 / 25 (4.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Performance Status Decreased

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

1 / 26 (3.85%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sudden Death

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Immune system disorders

Anaphylactic Reaction

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Social circumstances

Loss Of Personal Independence In Daily Activities

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

Prostatitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 18 (5.56%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pelvic Pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Acute Respiratory Failure

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

1 / 7 (14.29%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

2 / 109 (1.83%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Bronchospasm

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

2 / 109 (1.83%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Apnoea

subjects affected / exposed

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspnoea At Rest

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Dyspnoea Exertional

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Haemoptysis

subjects affected / exposed

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Laryngeal Oedema

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

1 / 7 (14.29%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Laryngospasm

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

1 / 7 (14.29%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pharyngeal Swelling

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural Effusion

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

2 / 109 (1.83%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

1 / 25 (4.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary Embolism

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

1 / 1

Respiratory Tract Haemorrhage

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Respiratory Alkalosis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary Fibrosis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Product issues

Device Malfunction

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Device Occlusion

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Blood Creatinine Increased

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 18 (5.56%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Blood Pressure Increased

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Fall

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infusion Related Reaction

subjects affected / exposed

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

6 / 109 (5.50%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

2 / 55 (3.64%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

6 / 6

0 / 0

1 / 1

0 / 0

2 / 2

deaths causally related to treatment / all

0 / 0

Joint Injury

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 18 (5.56%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Road Traffic Accident

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Post Procedural Complication

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Traumatic Fracture

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

1 / 25 (4.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute Coronary Syndrome

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

1 / 26 (3.85%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Acute Myocardial Infarction

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial Fibrillation

subjects affected / exposed

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

1 / 25 (4.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Stress Cardiomyopathy

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

1 / 7 (14.29%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac Failure

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tachycardia

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Cerebral Haemorrhage

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Dizziness

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Headache

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sciatica

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ischaemic Stroke

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Seizure

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal Cord Compression

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

2 / 109 (1.83%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Somnolence

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Syncope

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 6 (0.00%)

1 / 7 (14.29%)

1 / 18 (5.56%)

1 / 26 (3.85%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

4 / 109 (3.67%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile Neutropenia

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 18 (5.56%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Hyperviscosity Syndrome

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Thrombocytopenia

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Eye disorders

Eye Pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cataract

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Visual Impairment

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Diarrhoea

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Diverticular Perforation

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Gastrointestinal Haemorrhage

subjects affected / exposed

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal Amyloidosis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

1 / 25 (4.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intussusception

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ileus

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

1 / 25 (4.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Mechanical Ileus

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small Intestinal Obstruction

subjects affected / exposed

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

2 / 55 (3.64%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Obstruction Gastric

subjects affected / exposed

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Hyperbilirubinaemia

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholestasis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute Kidney Injury

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 18 (5.56%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 16 (6.25%)

0 / 7 (0.00%)

4 / 109 (3.67%)

2 / 25 (8.00%)

1 / 24 (4.17%)

1 / 23 (4.35%)

0 / 25 (0.00%)

3 / 55 (5.45%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 4

0 / 3

0 / 1

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 2

Chronic Kidney Disease

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal Failure

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endocrine disorders

Hypercalcaemia Of Malignancy

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Musculoskeletal Chest Pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bone Pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 18 (5.56%)

0 / 26 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

1 / 25 (4.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Back Pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

2 / 18 (11.11%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

1 / 25 (4.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal Pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pathological Fracture

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 18 (5.56%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

3 / 109 (2.75%)

2 / 25 (8.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 2

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pain In Extremity

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

2 / 55 (3.64%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Spinal Stenosis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Acute Sinusitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal Sepsis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atypical Pneumonia

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchiolitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Bronchitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

1 / 26 (3.85%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 23 (4.35%)

0 / 25 (0.00%)

3 / 55 (5.45%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Campylobacter Gastroenteritis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Covid-19 Pneumonia

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Device Related Infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia Sepsis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

1 / 25 (4.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis Rotavirus

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

1 / 25 (4.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemophilus Sepsis

subjects affected / exposed

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infectious Colitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 18 (5.56%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Herpes Zoster

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

1 / 26 (3.85%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infective Aortitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Influenza

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

2 / 24 (8.33%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Intervertebral Discitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lower Respiratory Tract Infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

2 / 109 (1.83%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Lower Respiratory Tract Infection Viral

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lung Infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 18 (5.56%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Meningitis Bacterial

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 16 (6.25%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Meningococcal Sepsis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

1 / 25 (4.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Otitis Media

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

1 / 26 (3.85%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Parainfluenzae Virus Infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

1 / 7 (14.29%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumococcal Bacteraemia

subjects affected / exposed

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumocystis Jirovecii Pneumonia

subjects affected / exposed

1 / 6 (16.67%)

0 / 7 (0.00%)

1 / 18 (5.56%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia Aspiration

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 18 (0.00%)

4 / 26 (15.38%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 16 (0.00%)

0 / 7 (0.00%)

8 / 109 (7.34%)

2 / 25 (8.00%)

4 / 24 (16.67%)

1 / 23 (4.35%)

0 / 25 (0.00%)

5 / 55 (9.09%)

occurrences causally related to treatment / all

1 / 1

0 / 0

2 / 4

0 / 0

1 / 1

0 / 0

4 / 10

0 / 2

0 / 4

0 / 1

0 / 0

1 / 5

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

Pneumonia Bacterial

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

2 / 109 (1.83%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia Mycoplasmal

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia Respiratory Syncytial Viral

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia Streptococcal

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

1 / 7 (14.29%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary Sepsis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pneumonia Viral

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory Syncytial Virus Infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Respiratory Tract Infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

3 / 109 (2.75%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

2 / 3

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

Septic Shock

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

1 / 1

Sepsis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 18 (5.56%)

2 / 26 (7.69%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

3 / 109 (2.75%)

0 / 25 (0.00%)

1 / 24 (4.17%)

4 / 23 (17.39%)

0 / 25 (0.00%)

2 / 55 (3.64%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 3

0 / 0

1 / 3

0 / 0

0 / 1

0 / 4

0 / 0

1 / 3

deaths causally related to treatment / all

0 / 0

2 / 2

0 / 0

Sinusitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Tracheobronchitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

2 / 109 (1.83%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Upper Respiratory Tract Infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

2 / 23 (8.70%)

1 / 25 (4.00%)

1 / 55 (1.82%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 1

deaths causally related to treatment / all

0 / 0

Urinary Tract Infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Varicella

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

1 / 26 (3.85%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Varicella Zoster Virus Infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Decreased Appetite

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dehydration

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

1 / 25 (4.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Electrolyte Imbalance

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypercalcaemia

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

1 / 16 (6.25%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour Lysis Syndrome

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 18 (5.56%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

0 / 109 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperuricaemia

subjects affected / exposed

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 18 (0.00%)

0 / 26 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 16 (0.00%)

0 / 7 (0.00%)

1 / 109 (0.92%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 25 (0.00%)

0 / 55 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Phase 1: Isatuximab 10mg/kg QW	Phase 1: Isatuximab 20mg/kg Q2W	Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)	Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)	Phase 1: Isatuximab 5mg/kg Q2W	Phase 1: Isatuximab 3mg/kg Q2W	Phase 1: Isatuximab <=1mg/kg Q2W	Phase 1: Isatuximab 20mg/kg QW	Phase 2 Stage 2: Isatuximab Alone	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W	Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W	Phase 2 Stage 1a: Isatuximab 3mg/kg Q2W	Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W	Phase 2 Stage 2: Isatuximab + Dexamethasone
Total subjects affected by non serious adverse events
subjects affected / exposed	6 / 6 (100.00%)	6 / 7 (85.71%)	18 / 18 (100.00%)	26 / 26 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)	16 / 16 (100.00%)	6 / 7 (85.71%)	92 / 109 (84.40%)	25 / 25 (100.00%)	23 / 24 (95.83%)	22 / 23 (95.65%)	24 / 25 (96.00%)	47 / 55 (85.45%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	1	0	0	0	0
Tumour Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Vascular disorders
Hypertension
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	2 / 18 (11.11%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	1 / 109 (0.92%)	1 / 25 (4.00%)	2 / 24 (8.33%)	3 / 23 (13.04%)	0 / 25 (0.00%)	4 / 55 (7.27%)
occurrences all number	2	0	2	1	0	0	1	0	1	1	8	3	0	4
Hot Flush
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	3 / 109 (2.75%)	2 / 25 (8.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	1	0	0	0	0	0	0	0	3	2	0	0	1	1
Flushing
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 16 (0.00%)	2 / 7 (28.57%)	5 / 109 (4.59%)	3 / 25 (12.00%)	1 / 24 (4.17%)	4 / 23 (17.39%)	4 / 25 (16.00%)	1 / 55 (1.82%)
occurrences all number	1	0	0	0	1	0	0	39	5	4	1	4	5	1
Hypotension
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	5 / 109 (4.59%)	1 / 25 (4.00%)	2 / 24 (8.33%)	3 / 23 (13.04%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	0	0	0	0	5	1	2	3	1	1
Pallor
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	1	0	0
Peripheral Coldness
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	0	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 18 (11.11%)	4 / 26 (15.38%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	8 / 109 (7.34%)	0 / 25 (0.00%)	2 / 24 (8.33%)	1 / 23 (4.35%)	0 / 25 (0.00%)	7 / 55 (12.73%)
occurrences all number	0	0	2	4	0	0	0	0	9	0	2	1	0	7
Chest Discomfort
subjects affected / exposed	2 / 6 (33.33%)	2 / 7 (28.57%)	1 / 18 (5.56%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	3 / 25 (12.00%)	4 / 24 (16.67%)	1 / 23 (4.35%)	6 / 25 (24.00%)	2 / 55 (3.64%)
occurrences all number	3	2	1	1	0	0	0	0	1	3	4	1	6	2
Chills
subjects affected / exposed	2 / 6 (33.33%)	0 / 7 (0.00%)	1 / 18 (5.56%)	3 / 26 (11.54%)	0 / 3 (0.00%)	1 / 6 (16.67%)	4 / 16 (25.00%)	0 / 7 (0.00%)	9 / 109 (8.26%)	8 / 25 (32.00%)	5 / 24 (20.83%)	3 / 23 (13.04%)	2 / 25 (8.00%)	4 / 55 (7.27%)
occurrences all number	3	0	1	3	0	1	6	0	10	12	6	5	2	5
Face Oedema
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0
Fatigue
subjects affected / exposed	4 / 6 (66.67%)	4 / 7 (57.14%)	5 / 18 (27.78%)	8 / 26 (30.77%)	1 / 3 (33.33%)	2 / 6 (33.33%)	8 / 16 (50.00%)	1 / 7 (14.29%)	18 / 109 (16.51%)	11 / 25 (44.00%)	7 / 24 (29.17%)	5 / 23 (21.74%)	9 / 25 (36.00%)	11 / 55 (20.00%)
occurrences all number	7	6	6	10	1	2	10	1	106	12	7	5	9	17
Implant Site Pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Feeling Hot
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 18 (11.11%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	0	0	2	1	0	0	0	0	0	0	0	0	1	0
Influenza Like Illness
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	2 / 109 (1.83%)	1 / 25 (4.00%)	2 / 24 (8.33%)	0 / 23 (0.00%)	0 / 25 (0.00%)	2 / 55 (3.64%)
occurrences all number	0	0	0	0	0	0	1	0	2	2	2	0	0	2
Malaise
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	2 / 24 (8.33%)	2 / 23 (8.70%)	0 / 25 (0.00%)	2 / 55 (3.64%)
occurrences all number	1	0	0	0	0	0	1	0	0	0	2	2	0	2
Injection Site Pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Non-Cardiac Chest Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	3 / 109 (2.75%)	0 / 25 (0.00%)	3 / 24 (12.50%)	0 / 23 (0.00%)	2 / 25 (8.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	3	0	4	0	2	0
Oedema Peripheral
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	3 / 18 (16.67%)	2 / 26 (7.69%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	5 / 109 (4.59%)	1 / 25 (4.00%)	5 / 24 (20.83%)	2 / 23 (8.70%)	2 / 25 (8.00%)	5 / 55 (9.09%)
occurrences all number	1	0	3	3	0	0	2	0	5	1	6	3	3	5
Pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	5 / 109 (4.59%)	2 / 25 (8.00%)	1 / 24 (4.17%)	1 / 23 (4.35%)	4 / 25 (16.00%)	3 / 55 (5.45%)
occurrences all number	0	1	0	1	0	0	1	0	5	2	2	1	5	3
Peripheral Swelling
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	1	0	0	1
Pyrexia
subjects affected / exposed	1 / 6 (16.67%)	1 / 7 (14.29%)	3 / 18 (16.67%)	5 / 26 (19.23%)	1 / 3 (33.33%)	0 / 6 (0.00%)	4 / 16 (25.00%)	0 / 7 (0.00%)	4 / 109 (3.67%)	4 / 25 (16.00%)	5 / 24 (20.83%)	3 / 23 (13.04%)	3 / 25 (12.00%)	7 / 55 (12.73%)
occurrences all number	1	1	4	6	1	0	4	0	4	4	6	3	3	7
Immune system disorders
Cytokine Release Syndrome
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Reproductive system and breast disorders
Nipple Pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Vulvovaginal Pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Bronchospasm
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	2 / 26 (7.69%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	5 / 109 (4.59%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	0	0	1	2	0	0	0	0	5	0	0	0	1	1
Epistaxis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	3 / 26 (11.54%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	6 / 109 (5.50%)	4 / 25 (16.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	3 / 25 (12.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	3	0	0	0	0	6	4	1	0	3	1
Dyspnoea Exertional
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	3 / 109 (2.75%)	3 / 25 (12.00%)	2 / 24 (8.33%)	1 / 23 (4.35%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	3	2	1	1	0
Dyspnoea
subjects affected / exposed	1 / 6 (16.67%)	3 / 7 (42.86%)	5 / 18 (27.78%)	4 / 26 (15.38%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 16 (12.50%)	0 / 7 (0.00%)	17 / 109 (15.60%)	8 / 25 (32.00%)	5 / 24 (20.83%)	5 / 23 (21.74%)	4 / 25 (16.00%)	7 / 55 (12.73%)
occurrences all number	2	3	7	5	0	1	4	0	19	8	6	6	4	7
Cough
subjects affected / exposed	3 / 6 (50.00%)	1 / 7 (14.29%)	2 / 18 (11.11%)	6 / 26 (23.08%)	1 / 3 (33.33%)	2 / 6 (33.33%)	3 / 16 (18.75%)	2 / 7 (28.57%)	19 / 109 (17.43%)	7 / 25 (28.00%)	10 / 24 (41.67%)	2 / 23 (8.70%)	8 / 25 (32.00%)	12 / 55 (21.82%)
occurrences all number	4	1	3	6	1	2	5	2	22	10	14	3	11	16
Hypoxia
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	1	1	0	0	0	1	0	0	0	0	0
Laryngeal Discomfort
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Laryngospasm
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Nasal Congestion
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 16 (0.00%)	1 / 7 (14.29%)	9 / 109 (8.26%)	4 / 25 (16.00%)	3 / 24 (12.50%)	0 / 23 (0.00%)	3 / 25 (12.00%)	2 / 55 (3.64%)
occurrences all number	0	0	1	0	1	0	0	1	10	5	5	0	3	2
Oropharyngeal Pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	3 / 109 (2.75%)	4 / 25 (16.00%)	4 / 24 (16.67%)	0 / 23 (0.00%)	0 / 25 (0.00%)	4 / 55 (7.27%)
occurrences all number	0	1	1	0	0	0	0	0	3	5	5	0	0	4
Productive Cough
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	1 / 7 (14.29%)	5 / 109 (4.59%)	3 / 25 (12.00%)	3 / 24 (12.50%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	4	0	0	1	0	0	1	1	5	3	3	0	2	0
Rhinitis Allergic
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	1 / 7 (14.29%)	3 / 109 (2.75%)	1 / 25 (4.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	0	1	0	0	0	0	1	3	1	0	1	0	1
Rhinorrhoea
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	3 / 18 (16.67%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	3 / 109 (2.75%)	1 / 25 (4.00%)	1 / 24 (4.17%)	1 / 23 (4.35%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	1	0	3	0	0	0	0	0	3	1	1	1	1	1
Throat Lesion
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Throat Tightness
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	0	1	0	0	0	0	0	0	1	0	1	0	1	1
Sinus Congestion
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 18 (11.11%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	2 / 25 (8.00%)	2 / 24 (8.33%)	1 / 23 (4.35%)	3 / 25 (12.00%)	3 / 55 (5.45%)
occurrences all number	0	0	2	0	0	0	0	0	1	3	2	1	3	4
Sneezing
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	2 / 109 (1.83%)	2 / 25 (8.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	1	0	0	0	0	0	2	2	1	0	0	1
Throat Irritation
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	5 / 109 (4.59%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	2 / 25 (8.00%)	3 / 55 (5.45%)
occurrences all number	0	1	0	0	0	0	0	0	5	1	2	0	2	3
Upper-Airway Cough Syndrome
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	1 / 25 (4.00%)	2 / 24 (8.33%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	1	1	3	0	0	0
Tracheal Stenosis
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Wheezing
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	2 / 18 (11.11%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	1 / 7 (14.29%)	0 / 109 (0.00%)	5 / 25 (20.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	3 / 25 (12.00%)	1 / 55 (1.82%)
occurrences all number	0	1	2	1	0	0	0	1	0	5	0	1	3	1
Psychiatric disorders
Abnormal Dreams
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Agitation
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 25 (0.00%)	2 / 55 (3.64%)
occurrences all number	0	0	0	1	0	0	1	0	1	0	1	0	0	2
Confusional State
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 18 (5.56%)	2 / 26 (7.69%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	2 / 109 (1.83%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	3 / 25 (12.00%)	0 / 55 (0.00%)
occurrences all number	1	0	1	2	0	0	0	0	2	0	0	0	3	0
Bradyphrenia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Anxiety
subjects affected / exposed	1 / 6 (16.67%)	1 / 7 (14.29%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	4 / 109 (3.67%)	1 / 25 (4.00%)	1 / 24 (4.17%)	1 / 23 (4.35%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	1	1	1	0	0	0	0	0	4	1	1	1	1	1
Depression
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	3 / 109 (2.75%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	1	0	0	1	0	3	0	1	0	0	1
Insomnia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	3 / 26 (11.54%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 16 (6.25%)	1 / 7 (14.29%)	2 / 109 (1.83%)	2 / 25 (8.00%)	6 / 24 (25.00%)	1 / 23 (4.35%)	3 / 25 (12.00%)	14 / 55 (25.45%)
occurrences all number	0	0	0	3	0	1	1	1	4	2	7	1	3	19
Restlessness
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	3	0	0	1	0	0	0	0	0	0	0	0	0	1
Nightmare
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Irritability
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0	0	0	1
Investigations
Carbon Monoxide Diffusing Capacity Decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0	0	0	0
Blood Creatinine Increased
subjects affected / exposed	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	1 / 109 (0.92%)	1 / 25 (4.00%)	2 / 24 (8.33%)	2 / 23 (8.70%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	1	0	1	0	0	2	0	2	2	2	2	0	1
Electrocardiogram T Wave Abnormal
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Lymphocyte Count Decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0	0	2	0	0	0	0	1	0	0
Platelet Count Decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	2 / 25 (8.00%)	0 / 24 (0.00%)	5 / 23 (21.74%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	9	1	0
Neutrophil Count Decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	2 / 23 (8.70%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	2	0	0
Qrs Axis Abnormal
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Weight Decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	3 / 26 (11.54%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	2 / 109 (1.83%)	2 / 25 (8.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	2 / 25 (8.00%)	2 / 55 (3.64%)
occurrences all number	0	0	0	3	0	0	0	0	2	2	0	1	2	2
Injury, poisoning and procedural complications
Accidental Overdose
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Contusion
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 16 (12.50%)	1 / 7 (14.29%)	2 / 109 (1.83%)	1 / 25 (4.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	0	0	3	1	3	1	0	1	1	1
Infusion Related Reaction
subjects affected / exposed	4 / 6 (66.67%)	4 / 7 (57.14%)	10 / 18 (55.56%)	12 / 26 (46.15%)	2 / 3 (66.67%)	3 / 6 (50.00%)	5 / 16 (31.25%)	3 / 7 (42.86%)	38 / 109 (34.86%)	14 / 25 (56.00%)	13 / 24 (54.17%)	9 / 23 (39.13%)	15 / 25 (60.00%)	20 / 55 (36.36%)
occurrences all number	4	4	13	12	2	4	7	74	41	14	17	11	16	21
Fall
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	2 / 109 (1.83%)	0 / 25 (0.00%)	2 / 24 (8.33%)	0 / 23 (0.00%)	3 / 25 (12.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	2	0	2	0	5	0
Joint Injury
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Procedural Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	1 / 7 (14.29%)	1 / 109 (0.92%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	1	0	0	0
Sports Injury
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Scapula Fracture
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Cardiac disorders
Bundle Branch Block Right
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Palpitations
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	2 / 55 (3.64%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0	0	0	3
Bradycardia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0	0	0	0
Right Ventricular Hypertrophy
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Angina Pectoris
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	1	0
Tachycardia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	3 / 109 (2.75%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	3 / 55 (5.45%)
occurrences all number	0	0	0	0	0	0	0	0	3	2	0	0	1	3
Sinus Tachycardia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	1
Nervous system disorders
Balance Disorder
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Amnesia
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Dizziness
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 18 (5.56%)	2 / 26 (7.69%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 16 (6.25%)	1 / 7 (14.29%)	3 / 109 (2.75%)	1 / 25 (4.00%)	1 / 24 (4.17%)	1 / 23 (4.35%)	3 / 25 (12.00%)	4 / 55 (7.27%)
occurrences all number	1	0	1	3	0	1	1	1	3	1	1	1	3	5
Cranial Nerve Paralysis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Cognitive Disorder
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	1 / 7 (14.29%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Dysgeusia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	2 / 16 (12.50%)	1 / 7 (14.29%)	0 / 109 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1	1	2	1	0	0	1	0	1	1
Head Discomfort
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Headache
subjects affected / exposed	0 / 6 (0.00%)	2 / 7 (28.57%)	2 / 18 (11.11%)	5 / 26 (19.23%)	1 / 3 (33.33%)	0 / 6 (0.00%)	5 / 16 (31.25%)	1 / 7 (14.29%)	15 / 109 (13.76%)	7 / 25 (28.00%)	5 / 24 (20.83%)	4 / 23 (17.39%)	7 / 25 (28.00%)	8 / 55 (14.55%)
occurrences all number	0	4	2	5	1	0	8	33	22	8	6	4	8	9
Paraesthesia
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	2 / 109 (1.83%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	2 / 25 (8.00%)	1 / 55 (1.82%)
occurrences all number	0	1	0	0	0	0	0	0	3	0	0	0	2	1
Mental Impairment
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypoaesthesia
subjects affected / exposed	0 / 6 (0.00%)	2 / 7 (28.57%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	4 / 109 (3.67%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	0	2	1	0	0	0	0	0	5	0	1	0	1	0
Peripheral Sensory Neuropathy
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	2 / 109 (1.83%)	0 / 25 (0.00%)	2 / 24 (8.33%)	2 / 23 (8.70%)	4 / 25 (16.00%)	5 / 55 (9.09%)
occurrences all number	0	0	0	0	0	0	1	0	2	0	2	2	4	5
Vith Nerve Paralysis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Toxic Encephalopathy
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Restless Legs Syndrome
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	1 / 7 (14.29%)	0 / 109 (0.00%)	1 / 25 (4.00%)	2 / 24 (8.33%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	5	0	0	1	0	0	0	2	0	1	2	1	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	4 / 18 (22.22%)	10 / 26 (38.46%)	0 / 3 (0.00%)	2 / 6 (33.33%)	6 / 16 (37.50%)	0 / 7 (0.00%)	4 / 109 (3.67%)	8 / 25 (32.00%)	3 / 24 (12.50%)	9 / 23 (39.13%)	8 / 25 (32.00%)	1 / 55 (1.82%)
occurrences all number	2	0	7	13	0	2	6	0	4	11	3	14	12	1
Thrombocytopenia
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 18 (5.56%)	3 / 26 (11.54%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 16 (12.50%)	0 / 7 (0.00%)	3 / 109 (2.75%)	0 / 25 (0.00%)	0 / 24 (0.00%)	2 / 23 (8.70%)	6 / 25 (24.00%)	1 / 55 (1.82%)
occurrences all number	2	0	2	4	0	1	2	0	3	0	0	2	9	2
Neutropenia
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 18 (5.56%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	5 / 109 (4.59%)	0 / 25 (0.00%)	1 / 24 (4.17%)	1 / 23 (4.35%)	3 / 25 (12.00%)	0 / 55 (0.00%)
occurrences all number	2	0	2	2	0	0	0	0	5	0	1	1	4	0
Eye disorders
Conjunctival Haemorrhage
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	1
Scleral Discolouration
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Diplopia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0	0	0	1
Dry Eye
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0	1	0	0	0
Lacrimation Increased
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	2 / 109 (1.83%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	2	0	1	0	2	0
Vision Blurred
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	1	0	0	2	0	2	0	0	0	0	0
Visual Impairment
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal Discomfort
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	1	0	0	0	0	0
Abdominal Distension
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 18 (5.56%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	1	0	1	1	0	0	0	0	1	0	0	1	1	1
Abdominal Pain
subjects affected / exposed	1 / 6 (16.67%)	1 / 7 (14.29%)	1 / 18 (5.56%)	4 / 26 (15.38%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	7 / 109 (6.42%)	3 / 25 (12.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	2 / 25 (8.00%)	1 / 55 (1.82%)
occurrences all number	1	1	1	4	0	0	1	0	8	3	0	1	2	2
Abdominal Pain Upper
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	2 / 24 (8.33%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	1	0	0	0	1	0	1	0	2	0	0	1
Abdominal Tenderness
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Dry Mouth
subjects affected / exposed	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	1 / 24 (4.17%)	1 / 23 (4.35%)	2 / 25 (8.00%)	1 / 55 (1.82%)
occurrences all number	1	1	0	1	0	0	1	0	1	0	1	1	2	1
Diarrhoea
subjects affected / exposed	1 / 6 (16.67%)	1 / 7 (14.29%)	4 / 18 (22.22%)	6 / 26 (23.08%)	1 / 3 (33.33%)	0 / 6 (0.00%)	3 / 16 (18.75%)	2 / 7 (28.57%)	23 / 109 (21.10%)	9 / 25 (36.00%)	7 / 24 (29.17%)	5 / 23 (21.74%)	5 / 25 (20.00%)	11 / 55 (20.00%)
occurrences all number	1	1	6	9	1	0	4	2	37	11	13	7	9	17
Constipation
subjects affected / exposed	2 / 6 (33.33%)	0 / 7 (0.00%)	1 / 18 (5.56%)	2 / 26 (7.69%)	2 / 3 (66.67%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	11 / 109 (10.09%)	2 / 25 (8.00%)	4 / 24 (16.67%)	6 / 23 (26.09%)	2 / 25 (8.00%)	4 / 55 (7.27%)
occurrences all number	2	0	1	2	2	0	1	0	13	3	4	6	2	4
Dyspepsia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 18 (11.11%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	2 / 109 (1.83%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	5 / 55 (9.09%)
occurrences all number	0	0	2	1	0	0	0	0	2	0	0	0	0	7
Gastrointestinal Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Dysphagia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	2 / 24 (8.33%)	0 / 23 (0.00%)	0 / 25 (0.00%)	2 / 55 (3.64%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	2	0	0	2
Gastrooesophageal Reflux Disease
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	1	0	0	0
Glossitis
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Glossodynia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Haemorrhoids
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	2 / 25 (8.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	2 / 25 (8.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	3	0	0	2	0
Nausea
subjects affected / exposed	4 / 6 (66.67%)	1 / 7 (14.29%)	6 / 18 (33.33%)	10 / 26 (38.46%)	1 / 3 (33.33%)	2 / 6 (33.33%)	4 / 16 (25.00%)	1 / 7 (14.29%)	16 / 109 (14.68%)	11 / 25 (44.00%)	9 / 24 (37.50%)	6 / 23 (26.09%)	7 / 25 (28.00%)	7 / 55 (12.73%)
occurrences all number	6	4	8	13	1	2	6	1	18	16	14	6	8	32
Mouth Ulceration
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Rectal Haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Vomiting
subjects affected / exposed	1 / 6 (16.67%)	1 / 7 (14.29%)	4 / 18 (22.22%)	6 / 26 (23.08%)	1 / 3 (33.33%)	1 / 6 (16.67%)	2 / 16 (12.50%)	1 / 7 (14.29%)	13 / 109 (11.93%)	7 / 25 (28.00%)	4 / 24 (16.67%)	1 / 23 (4.35%)	6 / 25 (24.00%)	3 / 55 (5.45%)
occurrences all number	2	2	5	7	1	1	2	1	15	9	7	1	10	3
Toothache
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	2 / 109 (1.83%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	2	0	1	0	1	0
Stomatitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	1 / 7 (14.29%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	2	0	0	1	0
Skin and subcutaneous tissue disorders
Actinic Keratosis
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	1	0	0	0	0
Dermatitis Contact
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	0
Dermatitis Acneiform
subjects affected / exposed	0 / 6 (0.00%)	2 / 7 (28.57%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0	0	0
Alopecia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Erythema
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 18 (11.11%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	2	1	0	0	0	0	0	0	0	0	0	1
Hair Texture Abnormal
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Hyperhidrosis
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 25 (4.00%)	3 / 55 (5.45%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	1	0	1	3
Pruritus
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 18 (5.56%)	2 / 26 (7.69%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	1 / 7 (14.29%)	3 / 109 (2.75%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	2 / 55 (3.64%)
occurrences all number	0	2	1	2	0	0	0	1	4	1	0	0	0	2
Pain Of Skin
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	0	0	0
Onychoclasis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	0	0	0	0	0
Rash
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	1 / 7 (14.29%)	5 / 109 (4.59%)	1 / 25 (4.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	0	0	0	0	0	0	1	5	1	0	1	0	1
Rash Maculo-Papular
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	2	0	1	0	0	0	1	0	0	0	0
Rash Macular
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	0	0	0	0	0
Rash Erythematous
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Rash Pruritic
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	1	0	0
Skin Disorder
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	1 / 7 (14.29%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Skin Ulcer
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Renal and urinary disorders
Acute Kidney Injury
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	1 / 23 (4.35%)	2 / 25 (8.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1	2	2	0
Urinary Incontinence
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	2	0
Pollakiuria
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	2 / 25 (8.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	2 / 18 (11.11%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	12 / 109 (11.01%)	3 / 25 (12.00%)	5 / 24 (20.83%)	3 / 23 (13.04%)	5 / 25 (20.00%)	5 / 55 (9.09%)
occurrences all number	1	0	2	1	0	0	0	0	15	5	7	3	5	10
Back Pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	7 / 18 (38.89%)	6 / 26 (23.08%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 16 (6.25%)	1 / 7 (14.29%)	20 / 109 (18.35%)	3 / 25 (12.00%)	7 / 24 (29.17%)	2 / 23 (8.70%)	3 / 25 (12.00%)	9 / 55 (16.36%)
occurrences all number	2	0	7	6	1	0	1	5	23	3	8	2	3	10
Bone Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	3 / 18 (16.67%)	4 / 26 (15.38%)	2 / 3 (66.67%)	0 / 6 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	10 / 109 (9.17%)	1 / 25 (4.00%)	3 / 24 (12.50%)	1 / 23 (4.35%)	2 / 25 (8.00%)	1 / 55 (1.82%)
occurrences all number	0	0	4	5	2	0	2	0	12	1	3	1	2	1
Bursitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Flank Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	2 / 26 (7.69%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	2	0	1	0	0	1	0	1	0	1	1
Groin Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 16 (6.25%)	0 / 7 (0.00%)	3 / 109 (2.75%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	3	0	0	1	0	0
Joint Swelling
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Limb Discomfort
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Muscle Fatigue
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	2	0	0	0	0	0
Muscle Spasms
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	3 / 26 (11.54%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	4 / 109 (3.67%)	0 / 25 (0.00%)	2 / 24 (8.33%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	3	0	0	3	0	0	1	0	5	0	2	0	0	1
Musculoskeletal Pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 18 (5.56%)	0 / 26 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	3 / 109 (2.75%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	2 / 55 (3.64%)
occurrences all number	0	1	1	0	1	0	0	0	5	1	0	0	1	2
Musculoskeletal Chest Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 18 (11.11%)	1 / 26 (3.85%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 16 (6.25%)	1 / 7 (14.29%)	9 / 109 (8.26%)	2 / 25 (8.00%)	1 / 24 (4.17%)	3 / 23 (13.04%)	1 / 25 (4.00%)	5 / 55 (9.09%)
occurrences all number	0	0	2	1	1	0	1	3	9	2	1	3	1	5
Muscular Weakness
subjects affected / exposed	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	2 / 109 (1.83%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	1	1	0	0	0	0	0	0	2	0	1	0	1	2
Myalgia
subjects affected / exposed	2 / 6 (33.33%)	1 / 7 (14.29%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	8 / 109 (7.34%)	1 / 25 (4.00%)	4 / 24 (16.67%)	0 / 23 (0.00%)	1 / 25 (4.00%)	3 / 55 (5.45%)
occurrences all number	3	1	0	1	0	0	1	0	10	1	7	0	1	3
Neck Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	0	1	1	1
Pain In Extremity
subjects affected / exposed	2 / 6 (33.33%)	0 / 7 (0.00%)	0 / 18 (0.00%)	3 / 26 (11.54%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	8 / 109 (7.34%)	4 / 25 (16.00%)	2 / 24 (8.33%)	2 / 23 (8.70%)	4 / 25 (16.00%)	10 / 55 (18.18%)
occurrences all number	3	0	0	3	0	0	2	0	8	5	2	2	4	13
Pathological Fracture
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	2 / 26 (7.69%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	4 / 109 (3.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	1	2	0	0	0	0	4	0	0	0	0	1
Spinal Osteoarthritis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	1
Spinal Pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	2 / 55 (3.64%)
occurrences all number	0	1	0	0	0	0	0	0	1	0	0	0	0	3
Infections and infestations
Gastroenteritis Viral
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	0	2
Bronchitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	3 / 18 (16.67%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	1 / 7 (14.29%)	6 / 109 (5.50%)	1 / 25 (4.00%)	2 / 24 (8.33%)	0 / 23 (0.00%)	1 / 25 (4.00%)	2 / 55 (3.64%)
occurrences all number	0	0	5	1	0	0	1	1	8	1	2	0	1	4
Angular Cheilitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Gingivitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Herpes Simplex
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	0	0	0	0	0
Lower Respiratory Tract Infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Influenza
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	4 / 109 (3.67%)	2 / 25 (8.00%)	1 / 24 (4.17%)	1 / 23 (4.35%)	0 / 25 (0.00%)	4 / 55 (7.27%)
occurrences all number	0	0	0	1	0	0	0	0	6	2	1	1	0	5
Hordeolum
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	1 / 7 (14.29%)	4 / 109 (3.67%)	2 / 25 (8.00%)	2 / 24 (8.33%)	1 / 23 (4.35%)	0 / 25 (0.00%)	7 / 55 (12.73%)
occurrences all number	0	0	0	0	0	0	0	8	7	2	3	1	0	8
Otitis Media
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 18 (11.11%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	1 / 7 (14.29%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	2	1	0	0	1	1	0	0	0	0	0	0
Oral Candidiasis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	2 / 25 (8.00%)	3 / 24 (12.50%)	2 / 23 (8.70%)	1 / 25 (4.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	0	0	0	0	0	3	3	2	1	1
Sinusitis
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 18 (5.56%)	2 / 26 (7.69%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	5 / 109 (4.59%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	1 / 25 (4.00%)	3 / 55 (5.45%)
occurrences all number	0	1	1	2	1	0	1	0	5	0	0	1	1	5
Rhinitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	5 / 109 (4.59%)	1 / 25 (4.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	1	0	0	0	0	0	5	1	0	1	0	1
Respiratory Tract Infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	3 / 109 (2.75%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	3 / 55 (5.45%)
occurrences all number	0	0	0	0	0	0	1	0	4	0	0	0	0	3
Pyuria
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	1 / 7 (14.29%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 16 (0.00%)	0 / 7 (0.00%)	5 / 109 (4.59%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	3 / 55 (5.45%)
occurrences all number	0	0	0	0	0	1	0	0	5	0	0	1	0	3
Tooth Abscess
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Tooth Infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	2 / 26 (7.69%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	2 / 109 (1.83%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	2	1	0	0	0	0
Urinary Tract Infection
subjects affected / exposed	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	8 / 109 (7.34%)	0 / 25 (0.00%)	1 / 24 (4.17%)	1 / 23 (4.35%)	2 / 25 (8.00%)	2 / 55 (3.64%)
occurrences all number	2	1	0	1	0	0	2	0	9	0	1	1	2	2
Upper Respiratory Tract Infection
subjects affected / exposed	3 / 6 (50.00%)	3 / 7 (42.86%)	3 / 18 (16.67%)	7 / 26 (26.92%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 16 (6.25%)	1 / 7 (14.29%)	14 / 109 (12.84%)	9 / 25 (36.00%)	7 / 24 (29.17%)	4 / 23 (17.39%)	6 / 25 (24.00%)	8 / 55 (14.55%)
occurrences all number	4	4	3	11	1	1	4	1	16	20	17	5	9	9
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	1 / 6 (16.67%)	1 / 7 (14.29%)	3 / 18 (16.67%)	5 / 26 (19.23%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 16 (0.00%)	1 / 7 (14.29%)	11 / 109 (10.09%)	3 / 25 (12.00%)	3 / 24 (12.50%)	4 / 23 (17.39%)	5 / 25 (20.00%)	4 / 55 (7.27%)
occurrences all number	1	1	4	5	1	0	0	1	11	3	4	4	5	4
Dehydration
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	3 / 109 (2.75%)	0 / 25 (0.00%)	4 / 24 (16.67%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	3	0	4	0	1	0
Hypercalcaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	3 / 24 (12.50%)	3 / 23 (13.04%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0	0	2	0	0	0	3	5	2	0
Hyperglycaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	3 / 109 (2.75%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	3 / 55 (5.45%)
occurrences all number	0	0	0	1	0	0	0	0	8	0	0	1	0	3
Hypophosphataemia
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 18 (5.56%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	1	0	0	1	0
Hypomagnesaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 18 (11.11%)	0 / 26 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	2	0	1	1	0	0	0	2	0	1	0	0
Hypokalaemia
subjects affected / exposed	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 18 (5.56%)	1 / 26 (3.85%)	1 / 3 (33.33%)	2 / 6 (33.33%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 109 (0.92%)	1 / 25 (4.00%)	3 / 24 (12.50%)	1 / 23 (4.35%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	1	1	3	2	0	0	2	1	3	1	0	0
Hypocalcaemia
subjects affected / exposed	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 25 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	1	0	0	4
Hyperuricaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	1 / 26 (3.85%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	3 / 23 (13.04%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	3	0	0
Hyperkalaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 18 (5.56%)	3 / 26 (11.54%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 25 (4.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	3	0	0	0	0	0	1	2	0	1	0
Pseudohyponatraemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 18 (0.00%)	0 / 26 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 109 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 25 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

16 Dec 2009

The definition of DLT was revised to include hematological toxicities. A procedure to notify investigators of DLTs and SAEs within 24 hours of occurrence was provided. Clarifications and revisions were incorporated to ensure the first 2 participants in a multiple-dose cohort would not receive study treatment on the same day. Updates were incorporated to remove participants from the study who had dose delays >2 weeks for an AE from study. The definition of participants who were considered unsuitable for standard first-line treatment but suitable for treatment with study treatment was clarified. An assessment of vital signs 6 hours following the first infusion of study treatment was added.

07 Apr 2010

Information regarding the Clinical Study Director was updated. The clinical trial summary, assessment schedule, and disease response evaluation were corrected. The PK/PD flowcharts were revised and corrections/updates were made. Clarifications were provided regarding the secondary endpoint(s) for PK samples. Appendix C was revised to reflect central labs. Minor edits for consistency in formatting were incorporated.

11 Oct 2010

The study design was revised to include intra-participant dose escalation. The main selection criteria were revised to exclude participants whose platelet counts were <50 × 10^9 /L for all indications. The study treatment infusion rate was clarified for all participants. The study flowcharts were revised. Minor edits for formatting consistency were incorporated.

05 Jan 2011

The study design was revised to remove intra-participant dose escalation. The main selection criteria for multiple myeloma were clarified to include participants with free light-chain disease. The main selection criteria were revised to exclude participants with platelet counts <50 × 10^9/L for all indications. The IP dilution and rate of infusion for participants were clarified. The study flowcharts were revised. Minor edits for formatting consistency were incorporated.

10 Sep 2012

The definition for DLT was modified to remove Grade 2 or higher allergic reaction/hypersensitivity attributed to SAR650984. The study flowchart for basic dose escalation was modified. The Guidelines for Management of Hypersensitivity Reactions were changed to include clarification for the management of hypersensitivity reactions in the setting of routine premedication with methylprednisolone, diphenhydramine, and acetaminophen. The dose of drug per administration was clarified to indicate that actual body weight was to be measured at each cycle and should be used for dose escalation. Routine premedication with dexamethasone and diphenhydramine for mild hypersensitivity reactions previously observed was instituted. It was clarified that the selection of disease assessment parameter was based on clinical indication and the judgment of the investigator. The timing of safety evaluations, including laboratory assessments and electrocardiograms, was clarified to be consistent with the study flowcharts. Minor edits for formatting and consistency were incorporated.

05 Apr 2013

Dose escalation and expansion cohorts were added. Updates were made to the eligibility criteria. New infusion rate information was added for the 20 mg/kg dose escalation cohort. Assessments schedules were added or updated. Other administrative changes and clarifications were incorporated.

13 Aug 2013

Exclusion criterion was clarified/added to better define required contraception. Information for the Clinical Study Director was updated.

19 Mar 2014

The dose modification guidance was changed to enable participants in the Phase 1 part of the study to be considered for intra-participant dose modifications if they had received treatment for at least 12 weeks on the current dose level and had no study treatment related AE >Grade 1. The frequency of chest X-ray, spirometry, and diffusion capacity was reduced to only being required during the first 2 cycles, and thereafter as clinically indicated. Minor edits for formatting and consistency were incorporated. Phase 2 was added to the study to allow seamless enrollment of participants after the standard risk expansion cohort had completed enrollment; a few changes related to Phase 2 were made.

08 Apr 2014

Phase 1 exclusion criterion and Phase 2 exclusion criterion: Clarified wording related to excipients to match Investigator’s Brochure (IB). A time window for the collection of PK samples was included. Minor edits for formatting and consistency were incorporated.

22 Aug 2014

Cohort 13 was added to the Phase 1 part of the study to enable evaluation of the 20 mg/kg weekly dose level. MRD and tumor cell CD38 messenger ribonucleic acid were added to the exploratory endpoints. The collection of an optional pharmacogenetics sample was added. The definition of adverse events of special interest (AESI) and overdose was clarified and updated based on the ongoing safety review. The definition of the high risk cohort was clarified (prior therapy inclusion requirements were clarified). The follow-up for related AEs and all SAEs ongoing at the time of study treatment discontinuation was clarified. The required assessments at 60 days and post-60 days after the last study treatment administration were clarified and harmonized. The guidelines for managing potential hypersensitivity reactions and potential tumor lysis syndrome (TLS) were clarified and harmonized with updated AESI language. The PK software used and PK parameters to be assessed were clarified. Minor edits for formatting and consistency were incorporated. An additional cohort was added to the Phase 2 part of the study to evaluate the dose of 20 mg/kg QW for 4 weeks followed by Q2W in 24 patients. Hereafter, there were 3 parts to the Phase 2 study. Clarified that Phase 1 and Phase 2 data were to be analyzed separately. Changed dose modification guidance to allow participants receiving 3/mg kg who had disease progression to escalate their dose if safety criteria were met. Immunoglobulin (Ig) D and IgE analyses were added. Study flowcharts were added/updated. Definitions added/clarified for AESIs, overdose, refractory disease, AESI, pregnancy.

22 Apr 2016

Serum pregnancy tests were added to the beginning of each cycle. A new section of contraceptive measures was added. The assessment of the study treatment was updated with general guidelines to be implements for infusion associated reactions and TLS. Appendix K was added to provide Investigators with background information and guidance regarding anti-CD38 interference with serologic testing. Minor edits for formatting and consistency were incorporated. Added a Phase 2 Stage 2 part: isatuximab alone (105 participants) or in combination with dexamethasone (55 participants). A few changes were applied to Stage 2.

12 Jul 2017

Estimated glomerular filtration rate exclusion criterion was changed. Permitted participants in Phase 2 Stage 1 to switch formulation after the study cutoff. Clarified data collection for participants continuing treatment after analysis cut off date. Clarified timing and assessments at follow-up visits. Modified schedule and /or analyses for PK, ADA, and urinalysis. Modified definition of infusion associated reaction and AESI. Clarified intervals for dose delays/modifications. Clarified instructions when eliminating premedications could be reconsidered. Clarified definition of treatment exposure. Appendices added/deleted/modified to support changes in the protocol. Clarified dose delay management during Cycle 1 QW dosing. Added exception to dose delay criteria resulting in permanent treatment discontinuation if a participant had objective clinical benefit and after Investigator and Sponsor discussion. Added assessment for blood type, phenotype, and antibody screen pretreatment.

11 Jun 2019

Based on updated PK characterization of isatuximab, the plasma half-life was re-estimated to 28 days. As duration of contraceptive measures was required to last for 5 half-lives, a revised duration of contraceptive measures and pregnancy testing of 5 months after the last isatuximab dose was required.

22 Jul 2020

A risk of hepatitis reactivation was identified in the SAR650984 IB edition 11 and the respective updates were made. Treatment supply option (oral dexamethasone provided to the participant via a Sponsor-approved courier company) for participants who were unable to come to the study site because of a regional or national emergency declared by a governmental agency. Clarification was added for only necessary copies of medical records (hospitalization and examination reports for SAEs were not to be systematically requested) to be shared with Sponsor. Since ADA were not tested beyond final analysis cutoff date, 30-day follow up sampling (30 days following last use of study drug) was considered sufficient.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase 1/2 Dose Escalation Safety, Pharmacokinetic and Efficacy Study of Multiple Intravenous Administrations of a Humanized Monoclonal Antibody (SAR650984) Against CD38 in Patients With Selected CD38+ Hematological Malignancies

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)

Primary: Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)

Primary: Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Primary: Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Primary: Phase 2 Stage 1: Percentage of Participants With Overall Response (OR) According to International Myeloma Working Group (IMWG) Uniform Response Criteria

Primary: Phase 2 Stage 1: Percentage of Participants With Overall Response (OR) According to International Myeloma Working Group (IMWG) Uniform Response Criteria

Primary: Phase 2 Stage 2: Percentage of Participants With Overall Response According to Updated IMWG Response Criteria

Primary: Phase 2 Stage 2: Percentage of Participants With Overall Response According to Updated IMWG Response Criteria

Secondary: Pharmacokinetic (PK) assessment: Phase 1: Plasma Concentration of Isatuximab observed at the end of an Intravenous infusion (Ceoi)

Secondary: Pharmacokinetic (PK) assessment: Phase 1: Plasma Concentration of Isatuximab observed at the end of an Intravenous infusion (Ceoi)

Secondary: PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab

Secondary: PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab

Secondary: PK Assessment: Phase 1: Time to reach maximum plasma concentration observed (tmax) of Isatuximab

Secondary: PK Assessment: Phase 1: Time to reach maximum plasma concentration observed (tmax) of Isatuximab

Secondary: PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3

Secondary: PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3

Secondary: PK Assessment: Phase 1: Predicted Cumulative Area under the plasma concentration Curve (AUC) of Isatuximab Over the First Week (0-168 hours) (AUC1W)

Secondary: PK Assessment: Phase 1: Predicted Cumulative Area under the plasma concentration Curve (AUC) of Isatuximab Over the First Week (0-168 hours) (AUC1W)

Secondary: PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 hours) (AUC2W)

Secondary: PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 hours) (AUC2W)

Secondary: Pharmacodynamic (PD) assessment: Phase 1: Change From Baseline in Serum/Plasma Markers

Secondary: Pharmacodynamic (PD) assessment: Phase 1: Change From Baseline in Serum/Plasma Markers

Secondary: Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response

Secondary: Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response

Secondary: Clinical assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) criteria

Secondary: Clinical assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) criteria

Secondary: Clinical assessment: Phase 1: Duration of response (DOR)

Secondary: Clinical assessment: Phase 1: Duration of response (DOR)

Secondary: Clinical assessment: Phase 1: Time to First Response (TTR)

Secondary: Clinical assessment: Phase 1: Time to First Response (TTR)

Secondary: Clinical assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Karnofsky performance status)-Shift From Baseline Value to Best Value During Treatment

Secondary: Clinical assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Karnofsky performance status)-Shift From Baseline Value to Best Value During Treatment

Secondary: Clinical assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky performance status)-Shift From Baseline Value to Worst Value During Treatment

Secondary: Clinical assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky performance status)-Shift From Baseline Value to Worst Value During Treatment

Secondary: Phase 2 Stage 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Secondary: Phase 2 Stage 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Secondary: Phase 2 Stage 1: Duration of Response

Secondary: Phase 2 Stage 1: Duration of Response

Secondary: Phase 2 Stage 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Secondary: Phase 2 Stage 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Secondary: Phase 2 Stage 2: Percentage of Participants With Clinical Benefit

Secondary: Phase 2 Stage 2: Percentage of Participants With Clinical Benefit

Secondary: Phase 2 Stage 1: Percentage of Participants With Clinical Benefit

Secondary: Phase 2 Stage 1: Percentage of Participants With Clinical Benefit

Secondary: Phase 2 Stage 2: Duration of Response

Secondary: Phase 2 Stage 2: Duration of Response

Secondary: Phase 2 Stage 1: Progression free survival (PFS)

Secondary: Phase 2 Stage 1: Progression free survival (PFS)

Secondary: Phase 2 Stage 2: Overall survival

Secondary: Phase 2 Stage 2: Overall survival

Secondary: Phase 2 Stage 1: Overall survival (OS)

Secondary: Phase 2 Stage 1: Overall survival (OS)

Secondary: Phase 2 Stage 2: Progression free survival

Secondary: Phase 2 Stage 2: Progression free survival

Secondary: Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status

Secondary: Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status

Secondary: Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score

Secondary: Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score

Secondary: Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores

Secondary: Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: Area under the plasma concentration versus time curve of Isatuximab over 1 week interval

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: Area under the plasma concentration versus time curve of Isatuximab over 1 week interval

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: Area under the plasma concentration versus time curve of Isatuximab over 2 weeks interval

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: Area under the plasma concentration versus time curve of Isatuximab over 2 weeks interval

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: Area under the plasma concentration versus time curve of Isatuximab over 4 weeks interval

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: Area under the plasma concentration versus time curve of Isatuximab over 4 weeks interval

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: Accumulation ratio of Isatuximab based on Ctrough

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: Accumulation ratio of Isatuximab based on Ctrough

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: plasma concentration of Isatuximab before treatment administration (Ctrough)

Secondary: Pharmacokinetic assessment: Phase 2 Stage 2: plasma concentration of Isatuximab before treatment administration (Ctrough)

Clinical Trial Results:
A Phase 1/2 Dose Escalation Safety, Pharmacokinetic and Efficacy Study of Multiple Intravenous Administrations of a Humanized Monoclonal Antibody (SAR650984) Against CD38 in Patients With Selected CD38+ Hematological Malignancies