Download PDF

Clinical Trial Results:
A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination with Polatuzumab Vedotin and Venetoclax in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination with Polatuzumab Vedotin and Venetoclax in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Summary
EudraCT number	2015-001998-40
Trial protocol	IT
Global end of trial date	04 Aug 2022

Results information
Results version number	v2(current)
This version publication date	07 Apr 2024
First version publication date	16 Aug 2023
Other versions	v1
Version creation reason	Correction of full data set To align with updates made to the CT.gov record post NIH QA comments.

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

GO29833

ISRCTN number

US NCT number

NCT02611323

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, + 41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, + 41 616878333, global.trial_information@roche.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

04 Aug 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

04 Aug 2022

Was the trial ended prematurely?

Main objective of the trial

The main objective of the trial was to evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and venetoclax in participants with relapsed or refractory FL, and with rituximab, polatuzumab vedotin, and venetoclax in participants with DLBCL.

Protection of trial subjects

All participants were required to sign the informed consent form (ICF).

Background therapy

Evidence for comparator

Actual start date of recruitment

09 Mar 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 53

Country: Number of subjects enrolled

Italy: 29

Country: Number of subjects enrolled

United States: 49

Worldwide total number of subjects

131

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Participants took part in this study at 23 investigative centers in Australia, Italy, & the United States from 09 March 2016 to 04 August 2022. Study consisted of two phases: dose-escalation phase & dose-expansion phase. All eligible participants in both the phases received induction treatment, & post-induction treatment as indicated.

Screening details

Participants were enrolled in in the study to receive polatuzumab vedotin + venetoclax & fixed doses of rituximab/obinutuzumab. Of the 133 enrolled participants, 131 participants received at least one dose of the study drug & their intended treatment. 2 participants did not receive any study treatment.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

FL Dose Escalation: 1.4P+400V+1000G

Arm description

Participants received venetoclax, 400 milligrams (mg), orally, once daily (QD) on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, intravenous (IV) infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.4 milligrams per kilograms (mg/kg), IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved complete response (CR), partial response (PR), or stable disease (SD) at end of induction (EOI) received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 400 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months.

Arm type

Experimental

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199; RO5537382

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received venetoclax, 400 mg, orally, QD on Days 1-21 of Cycles 1-6 followed by maintenance treatment (for participants with CR, PR or SD) at a dose of 400 mg, orally, QD until disease progression or unacceptable toxicity for up to 8 months.

Investigational medicinal product name

Obinituzumab

Investigational medicinal product code

Other name

RO5072759

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received obinutuzumab, 1000 mg, IV infusion on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 followed by maintenance treatment (only for participants with CR, PR or SD) at a dose of 1000 mg via IV infusion on Day 1 of every other month until disease progression or unacceptable toxicity for up to 24 months.

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

DCDS4501A

Other name

RO5541077

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received polatuzumab vedotin, 1.4 mg/kg, IV infusion on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

FL Dose Escalation: 1.4P+200V+1000G

Arm description

Participants received venetoclax, 200 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.4 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 200 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

DCDS4501A

Other name

RO5541077

Pharmaceutical forms

Infusion, Infusion

Routes of administration

Intravenous use, Intravenous use

Dosage and administration details

Participants received polatuzumab vedotin, 1.4 mg/kg, IV infusion on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Investigational medicinal product name

Obinituzumab

Investigational medicinal product code

Other name

RO5072759

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199; RO5537382

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

FL Dose Escalation: 1.8P+400V+1000G

Arm description

Participants received venetoclax, 400 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 400 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

DCDS4501A

Other name

RO5541077

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received polatuzumab vedotin, 1.8 mg/kg, IV infusion on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Investigational medicinal product name

Obinituzumab

Investigational medicinal product code

Other name

RO5072759

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199; RO5537382

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

FL Dose Escalation: 1.4P+600V+1000G

Arm description

Participants received venetoclax, 600 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.4 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 600 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months.

Arm type

Experimental

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199; RO5537382

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Obinituzumab

Investigational medicinal product code

Other name

RO5072759

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

DCDS4501A

Other name

RO5541077

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received polatuzumab vedotin, 1.4 mg/kg, IV infusion on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

FL Dose Escalation: 1.8P+600V+1000G

Arm description

Participants received venetoclax, 600 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 600 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

DCDS4501A

Other name

RO5541077

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received polatuzumab vedotin, 1.8 mg/kg, IV infusion on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Investigational medicinal product name

Obinituzumab

Investigational medicinal product code

Other name

RO5072759

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199; RO5537382

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

FL Dose Escalation: 1.8P+800V+1000G

Arm description

Participants received venetoclax, 800 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 800 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

DCDS4501A

Other name

RO5541077

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received polatuzumab vedotin, 1.8 mg/kg, IV infusion on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Investigational medicinal product name

Obinituzumab

Investigational medicinal product code

Other name

RO5072759

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199; RO5537382

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

FL: Dose Expansion: 1.8P+800V+1000G

Arm description

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

DCDS4501A

Other name

RO5541077

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received polatuzumab vedotin, 1.8 mg/kg, IV infusion on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Investigational medicinal product name

Obinituzumab

Investigational medicinal product code

Other name

RO5072759

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199; RO5537382

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

DLBCL: Dose Escalation: 1.8P+400V+375R

Arm description

Participants received venetoclax, 400 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with rituximab, 375 milligrams per square metre (mg/m^2), IV infusion, on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 8 months. During consolidation treatment participants received venetoclax, 400 mg, QD, for up to 8 months and rituximab, 375 mg/m^2 on Day 1 of every other month (1 month=28 days) starting from Month 2 up to 8 months.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

DCDS4501A

Other name

RO5541077

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received polatuzumab vedotin, 1.8 mg/kg, IV infusion on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

RO0452294

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received rituximab, 375 mg/m^2, IV, infusion on Day 1 of Cycle 1 to 6 followed by consolidation treatment (for participants with CR or PR) at a dose of 375 mg/m^2 via IV infusion on Day 1 of every other month until disease progression or unacceptable toxicity for up to 8 months.

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199; RO5537382

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received venetoclax, 400 mg, orally, QD on Days 1-21 of Cycles 1-6 followed by consolidation treatment (for participants with CR or PR) at a dose of 400 mg, orally, QD until disease progression or unacceptable toxicity for up to 8 months.

DLBCL Dose Escalation: 1.8P+600V+375R

Arm description

Participants received venetoclax, 600 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with rituximab, 375 mg/m^2, IV infusion, on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 8 months. During consolidation treatment participants received venetoclax, 600 mg, QD, for up to 8 months and rituximab, 375 mg/m^2 on Day 1 of every other month (1 month=28 days) starting from Month 2 up to 8 months.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

DCDS4501A

Other name

RO5541077

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received polatuzumab vedotin, 1.8 mg/kg, IV infusion on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199; RO5537382

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received venetoclax, 600 mg, orally, QD on Days 1-21 of Cycles 1-6 followed by consolidation treatment (for participants with CR or PR) at a dose of 400 mg, orally, QD until disease progression or unacceptable toxicity for up to 8 months.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

RO0452294

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

DLBCL Dose Escalation: 1.8P+800V+375R

Arm description

Participants received venetoclax, 800 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with rituximab, 375 mg/m^2, IV infusion, on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 8 months. During consolidation treatment participants received venetoclax, 800 mg, QD, for up to 8 months and rituximab, 375 mg/m^2 on Day 1 of every other month (1 month=28 days) starting from Month 2 up to 8 months.

Arm type

Experimental

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

DCDS4501A

Other name

RO5541077

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received polatuzumab vedotin, 1.8 mg/kg, IV infusion on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199; RO5537382

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received venetoclax, 800 mg, orally, QD on Days 1-21 of Cycles 1-6 followed by consolidation treatment (for participants with CR or PR) at a dose of 400 mg, orally, QD until disease progression or unacceptable toxicity for up to 8 months.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

RO0452294

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

DLBCL Dose Expansion: 1.8P+800V+375R

Arm description

Arm type

Experimental

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

RO0452294

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199; RO5537382

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Investigational medicinal product name

Polatuzumab vedotin

Investigational medicinal product code

DCDS4501A

Other name

RO5541077

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received polatuzumab vedotin, 1.8 mg/kg, IV infusion on Day 1 of each 28-day cycle for up to 6 cycles during induction treatment.

Number of subjects in period 1	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL: Dose Escalation: 1.8P+400V+375R	DLBCL Dose Escalation: 1.8P+600V+375R	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Started	7	3	3	3	9	8	41	3	6	8	40
Completed	2	2	3	3	8	7	30	2	2	0	11
Not completed	5	1	0	0	1	1	11	1	4	8	29
Adverse event, serious fatal	3	1	-	-	1	1	8	-	4	6	26
Consent withdrawn by subject	1	-	-	-	-	-	-	1	-	1	-
Progressive Disease	-	-	-	-	-	-	-	-	-	-	1
Lost to follow-up	1	-	-	-	-	-	3	-	-	-	2
Found Another Malignancy After Starting Trial	-	-	-	-	-	-	-	-	-	1	-

Baseline characteristics

Top of page

Reporting group title

FL Dose Escalation: 1.4P+400V+1000G

Reporting group description

Reporting group title

FL Dose Escalation: 1.4P+200V+1000G

Reporting group description

Reporting group title

FL Dose Escalation: 1.8P+400V+1000G

Reporting group description

Reporting group title

FL Dose Escalation: 1.4P+600V+1000G

Reporting group description

Reporting group title

FL Dose Escalation: 1.8P+600V+1000G

Reporting group description

Participants received venetoclax, 600 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 600 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months.

Reporting group title

FL Dose Escalation: 1.8P+800V+1000G

Reporting group description

Reporting group title

FL: Dose Expansion: 1.8P+800V+1000G

Reporting group description

Reporting group title

DLBCL: Dose Escalation: 1.8P+400V+375R

Reporting group description

Reporting group title

DLBCL Dose Escalation: 1.8P+600V+375R

Reporting group description

Reporting group title

DLBCL Dose Escalation: 1.8P+800V+375R

Reporting group description

Reporting group title

DLBCL Dose Expansion: 1.8P+800V+375R

Reporting group description

Reporting group values	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL: Dose Escalation: 1.8P+400V+375R	DLBCL Dose Escalation: 1.8P+600V+375R	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R	Total
Number of subjects	7	3	3	3	9	8	41	3	6	8	40	131
Age categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	58.9 ( 6.8 )	61.3 ( 8.5 )	56.7 ( 13.6 )	58.3 ( 10.3 )	64.6 ( 6.1 )	58.0 ( 11.9 )	62.2 ( 11.3 )	56.0 ( 16.5 )	58.7 ( 17.4 )	67.4 ( 15.2 )	65.8 ( 9.6 )	-
Sex: Female, Male
Units: participants
Female	3	1	0	0	4	4	20	2	4	5	18	61
Male	4	2	3	3	5	4	21	1	2	3	22	70
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0	1	0	0	1	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	1	0	0	1	2	4
White	7	3	3	3	8	7	34	2	6	6	30	109
More than one race	0	0	0	0	0	0	0	0	0	0	1	1
Unknown or Not Reported	0	0	0	0	1	1	6	0	0	1	6	15
Race/Ethnicity, Customized
Units: Subjects
Hispanic or Latino	0	0	0	0	0	0	3	0	0	0	0	3
Not Hispanic or Latino	7	3	3	3	8	8	30	3	6	7	31	109
Not Stated	0	0	0	0	1	0	6	0	0	1	6	14
Unknown	0	0	0	0	0	0	2	0	0	0	3	5

End points

Top of page

Reporting group title

FL Dose Escalation: 1.4P+400V+1000G

Reporting group description

Reporting group title

FL Dose Escalation: 1.4P+200V+1000G

Reporting group description

Reporting group title

FL Dose Escalation: 1.8P+400V+1000G

Reporting group description

Reporting group title

FL Dose Escalation: 1.4P+600V+1000G

Reporting group description

Reporting group title

FL Dose Escalation: 1.8P+600V+1000G

Reporting group description

Participants received venetoclax, 600 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 600 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months.

Reporting group title

FL Dose Escalation: 1.8P+800V+1000G

Reporting group description

Reporting group title

FL: Dose Expansion: 1.8P+800V+1000G

Reporting group description

Reporting group title

DLBCL: Dose Escalation: 1.8P+400V+375R

Reporting group description

Reporting group title

DLBCL Dose Escalation: 1.8P+600V+375R

Reporting group description

Reporting group title

DLBCL Dose Escalation: 1.8P+800V+375R

Reporting group description

Reporting group title

DLBCL Dose Expansion: 1.8P+800V+375R

Reporting group description

Subject analysis set title

All FL Participants: Dose Escalation

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants with FL received venetoclax, at a dose of 200 mg, 400 mg, 600 mg or 800 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) in combination with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, at a dose of 1.4 mg/kg or 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, at a dose of 200 mg, 400 mg, 600 mg or 800 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months.

Subject analysis set title

All DLBCL Participants: Dose Escalation

Subject analysis set type

Sub-group analysis

Subject analysis set description

All participants with DLBCL received venetoclax, at a dose of 400 mg, 600 mg or 800 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with rituximab, 375 mg/m^2, IV infusion, on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR or PR at EOI received consolidation treatment until disease progression or unacceptable toxicity for up to 8 months. During consolidation treatment participants received venetoclax, at a dose of 400 mg, 600 mg or 800 mg, QD, for up to 8 months and rituximab, 375 mg/m^2 on Day 1 of every other month (1 month=28 days) starting from Month 2 up to 8 months.

Primary: Percentage of Participants with CR at EOI Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans

Top of page

End point title

Percentage of Participants with CR at EOI Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans ^[1] ^[2]

End point description

CR at EOI was assessed by IRC according to modified Lugano Response Criteria (MLRC) for Malignant Lymphoma 2014 using PET-CT scan. CR =complete metabolic response (MR) in lymph nodes & extra lymphatic sites (ELS) with a score of 1, 2, or 3, with/without a residual mass on PET 5-point scale (5-PS), where 1=no uptake above background; 2= uptake ≤mediastinum; 3= uptake >mediastinum but ≤liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver &/or new lesions. No new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Efficacy evaluable population=participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin & venetoclax at recommended phase 2 dose (RP2D) in dose-escalation phase were also analysed in addition to expansion phase participants for efficacy analysis. Percentages have been rounded off to first decimal point.

End point type

Primary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21 days)

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: It included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.
[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: It included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.

End point values	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	8	41	8	40
Units: percentage of participants
number (confidence interval 90%)	100 (68.77 to 100.00)	51.2 (37.44 to 64.86)	25 (4.64 to 59.97)	32.5 (20.41 to 46.63)

No statistical analyses for this end point

Primary: FL Cohorts: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Top of page

End point title

FL Cohorts: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) ^[3] ^[4]

End point description

An AE = as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any new disease or worsening of an existing disease were also considered as AEs. An SAE = any AE that was fatal, life threatening, required prolonged inpatient hospitalization, resulted in significant disability or resulted in a congenital anomaly to a mother exposed to study treatment. AEs and SAEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0). Percentages have been rounded off to the first decimal point. Safety-evaluable population included all participants who received at least one dose of any component of the combination.

End point type

Primary

End point timeframe

From study start to 24 months after last dose of study drug (approximately 56 months)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No descriptive statistics were planned.
[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 FL cohorts were included in this endpoint,

End point values	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G
Number of subjects analysed	7	3	3	3	9	8	41
Units: percentage of participants
number (not applicable)
AEs	100	100	100	100	100	100	100
SAEs	57.1	33.3	33.3	0	22.2	75.0	34.1

No statistical analyses for this end point

Primary: DLBCL Cohorts: Percentage of Participants with AEs and SAEs

Top of page

End point title

DLBCL Cohorts: Percentage of Participants with AEs and SAEs ^[5] ^[6]

End point description

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any new disease or worsening of an existing disease were also considered as AEs. An SAE was defined as any AE that was fatal, life threatening, requires prolonged inpatient hospitalization, resulted in significant disability or resulted in a congenital anomaly to a mother exposed to study treatment. AEs and SAEs were reported based on the NCI-CTCAE, v4.0. Percentages have been rounded off to the first decimal point. Safety-evaluable population included all participants who received at least one dose of any component of the combination.

End point type

Primary

End point timeframe

From study start to 3 months after last dose of study drug (approximately 21 months)

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: No descriptive statistics were planned.
[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 DLBCL cohorts were included in this endpoint,

End point values	DLBCL: Dose Escalation: 1.8P+400V+375R	DLBCL Dose Escalation: 1.8P+600V+375R	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	3	6	8	40
Units: percentage of participants
number (not applicable)
AEs	100	100	87.5	97.5
SAEs	100	66.7	25.0	30.0

No statistical analyses for this end point

Primary: RP2D of Polatuzumab Vedotin

Top of page

End point title

RP2D of Polatuzumab Vedotin ^[7]

End point description

RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase. The RP2D of polatuzumab vedotin when given in combination with fixed dose of obinutuzumab in participants with FL was determined. Safety-evaluable population included all participants who received at least one dose of any component of the combination.

End point type

Primary

End point timeframe

Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase

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: Only participants receiving polatuzumab vedotin have been included in this analysis.

End point values	All FL Participants: Dose Escalation
Number of subjects analysed	33
Units: mg/kg
number (not applicable)	1.8

No statistical analyses for this end point

Primary: Number of Participants with Dose-Limiting Toxicities (DLTs )

Top of page

End point title

Number of Participants with Dose-Limiting Toxicities (DLTs ) ^[8] ^[9]

End point description

DLT=any one of the events that occurred in first treatment cycle & per the investigator was related to study treatment. Any AE that lead to a delay of > 14 days in start of next treatment cycle; Any Grade 3/4 non-hematologic AE with few exceptions; Any increase in hepatic transaminase >3×baseline(BL) & increase in direct bilirubin >2×upper limit of normal (ULN), without any findings of cholestasis/jaundice/signs of hepatic dysfunction & in absence of other contributory factors; Grade1 alanine transaminase (ALT)/aspartate transaminase (AST) elevation at BL as result of liver metastases, only a Grade ≥3 elevation, also ≥3×BL lasting >7 days; Hematologic AE meeting protocol specified criteria. Events were graded per National Cancer Institute Common Terminology Criteria for AEs, version 4.0 NCI CTCAE v4.0. Safety-evaluable population=all participants who received at least one dose of any component of the combination.

End point type

Primary

End point timeframe

Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No descriptive statistics were planned.
[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: This endpoint is applicable only for FL and some DLBCL arms.

End point values	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	DLBCL: Dose Escalation: 1.8P+400V+375R	DLBCL Dose Escalation: 1.8P+600V+375R	DLBCL Dose Escalation: 1.8P+800V+375R
Number of subjects analysed	7	3	3	3	9	8	3	6	8
Units: participants	1	0	0	0	2	1	0	1	0

No statistical analyses for this end point

Primary: RP2D of Venetoclax

Top of page

End point title

RP2D of Venetoclax ^[10]

End point description

RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase. The RP2D of venetoclax when given in combination with fixed dose of polatuzumab vedotin in participants with FL and DLBCL was determined. Safety-evaluable population included all participants who received at least one dose of any component of the combination.

End point type

Primary

End point timeframe

Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only participants receiving venetoclax have been included in this analysis.

End point values	All FL Participants: Dose Escalation	All DLBCL Participants: Dose Escalation
Number of subjects analysed	33	17
Units: mg	800	800

No statistical analyses for this end point

Secondary: Percentage of Participants with CR at EOI, Determined by the Investigator on the Basis of PET-CT scans

Top of page

End point title

Percentage of Participants with CR at EOI, Determined by the Investigator on the Basis of PET-CT scans ^[11]

End point description

CR at EOI was assessed by Investigator according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions; no evidence of FDG-avid disease in bone marrow. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Efficacy evaluable population included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analysed in addition to expansion phase participants for efficacy analysis. Percentages have been rounded off to first decimal point.

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)

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: It included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.

End point values	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	8	41	8	40
Units: percentage of participants
number (confidence interval 90%)	100 (68.77 to 100.00)	51.2 (37.44 to 64.86)	25.0 (4.64 to 59.97)	32.5 (20.41 to 46.63)

No statistical analyses for this end point

Secondary: Percentage of Participants with CR at EOI, Determined by the IRC on the Basis of CT Scans Alone

Top of page

End point title

Percentage of Participants with CR at EOI, Determined by the IRC on the Basis of CT Scans Alone ^[12]

End point description

CR at EOI was determined by IRC according to the MLRC. Per MLRC, CR based on CT = complete radiologic response in lymph nodes & ELS with target nodes/nodal masses regressing to ≤ 1.5 centimeter (cm) in longest transverse diameter (LDi) & no ELS of disease; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, immunohistochemistry (IHC) negative. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Efficacy evaluable population included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analysed in addition to expansion phase participants for efficacy analysis. Overall number analysed is the number of participants with data available for analysis. Percentages have been rounded off to the first decimal point.

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)

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: It included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.

End point values	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	8	41	6	34
Units: percentage of participants
number (confidence interval 90%)	62.5 (28.92 to 88.89)	36.6 (24.08 to 50.61)	16.7 (0.85 to 58.18)	26.5 (14.56 to 41.65)

No statistical analyses for this end point

Secondary: Percentage of Participants with CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone

Top of page

End point title

Percentage of Participants with CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone ^[13]

End point description

CR at EOI was determined by Investigator according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Efficacy evaluable population included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analysed in addition to expansion phase participants for efficacy analysis. Percentages have been rounded off to the first decimal point.

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)

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: It included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.

End point values	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	8	41	8	40
Units: percentage of participants
number (confidence interval 90%)	75.0 (40.03 to 95.36)	29.3 (17.84 to 43.07)	25.0 (4.64 to 59.97)	22.5 (12.27 to 35.98)

No statistical analyses for this end point

Secondary: Percentage of Participants with Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans

Top of page

End point title

Percentage of Participants with Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans ^[14]

End point description

OR=% of participants with CR/PR as assessed=IRC per MLRC. Per MLRC CR per PET-CT=complete MR in lymph nodes &ELS with score of 1/2/3 with/without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤mediastinum; 3=uptake>mediastinum but ≤liver; 4=uptake moderately >liver5=uptake markedly >than liver &/or new lesions;no evidence of FDG-avid disease in bone marrow. PR per PET-CT=partial MR in lymph nodes &ELS with score of 4/5 with < uptake compared with BL & residual masses of any size: at interim/end of treatment, residual uptake >than uptake in normal bone marrow but <compared to BL. Efficacy evaluable population=participants in dose expansion arms who received at least one dose of any component of the combination. As pre-specified in protocol, participants who received polatuzumab vedotin & venetoclax at RP2D in dose-escalation were also analysed in addition to expansion phase participants for efficacy analysis. Percentages are rounded off to first decimal point

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)

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: It included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.

End point values	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	8	41	8	40
Units: percentage of participants
number (confidence interval 90%)	100.0 (68.77 to 100.00)	70.7 (56.93 to 82.16)	25.0 (4.64 to 59.97)	37.5 (24.73 to 51.72)

No statistical analyses for this end point

Secondary: Percentage of Participants with OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans

Top of page

End point title

Percentage of Participants with OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans ^[15]

End point description

OR=participants with CR/PR as assessed=IRC per MLRC. Per MLRC CR based on PET-CT=complete MR in lymph nodes &ELS with score of 1/2/3 with/without residual mass on 5PS,where 1=no uptake above background;2=uptake ≤mediastinum;3=uptake>mediastinum but ≤liver; 4=uptake moderately >liver5=uptake markedly >than liver &/or new lesions;no evidence of FDG-avid disease in bone marrow. PR per PET-CT=partial MR in lymph nodes &ELS with score of 4/5 with < uptake compared with BL &residual masses of any size: at interim/end of treatment, residual uptake >than uptake in normal bone marrow but <compared to BL. Efficacy evaluable population=participants in dose expansion arms who received at least one dose of any component of the combination. As pre-specified in protocol, participants who received polatuzumab vedotin & venetoclax at RP2D in dose-escalation were also analysed in addition to expansion phase participants for efficacy analysis. Percentages are rounded off to first decimal point.

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)

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: It included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.

End point values	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	8	41	8	40
Units: percentage of participants
number (confidence interval 90%)	100.0 (68.77 to 100.00)	75.6 (62.15 to 86.13)	37.5 (11.11 to 71.08)	42.5 (29.18 to 56.69)

No statistical analyses for this end point

Secondary: Percentage of Participants with OR at EOI, Determined by an IRC on the Basis of CT Scans Alone

Top of page

End point title

Percentage of Participants with OR at EOI, Determined by an IRC on the Basis of CT Scans Alone ^[16]

End point description

OR=% of participants with CR/PR, per IRC per MLRC. Per MLRC, CR per CT=complete radiologic response in lymph nodes & ELS with target nodes/nodal masses regressing to ≤1.5 cm in LDi &no ELS of disease; organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT=partial remission in lymph nodes & ELS with ≥50% decrease in sum of products of greatest diameters (SPD) of up to 6 target measurable lymph nodes & extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal, no new sites of lesions. Efficacy evaluable population included participants in dose expansion arms who received at least one dose of any component of the combination. As pre-specified in protocol, participants who received polatuzumab vedotin & venetoclax at RP2D in dose-escalation phase were also analysed in addition to expansion phase participants for efficacy analysis.

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)

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: It included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.

End point values	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	8	41	8	40
Units: percentage of participants
number (confidence interval 90%)	87.5 (52.93 to 99.36)	82.9 (70.31 to 91.70)	25.0 (4.64 to 59.97)	37.5 (24.73 to 51.72)

No statistical analyses for this end point

Secondary: Percentage of Participants with OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone

Top of page

End point title

Percentage of Participants with OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone ^[17]

End point description

OR=% of participants with CR/PR, per IRC per MLRC. Per MLRC, CR per CT=complete radiologic response in lymph nodes & ELS with target nodes/nodal masses regressing to ≤1.5 cm in LDi &no ELS of disease; organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT=partial remission in lymph nodes & ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes &extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal, no new sites of lesions. Efficacy evaluable population=participants in dose expansion arms who received at least one dose of any component of the combination. As pre-specified in protocol, participants who received polatuzumab vedotin &venetoclax at RP2D in dose-escalation phase were also analysed in addition to expansion phase participants for efficacy analysis. Percentages are rounded off to first decimal point.

End point type

Secondary

End point timeframe

6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)

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: It included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.

End point values	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	8	41	8	40
Units: percentage of participants
number (confidence interval 90%)	87.5 (52.93 to 99.36)	85.4 (73.15 to 93.43)	37.5 (11.11 to 71.08)	45.0 (31.46 to 59.12)

No statistical analyses for this end point

Secondary: Percentage of Participants with Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone

Top of page

End point title

Percentage of Participants with Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone ^[18]

End point description

BOR=CR/PR per investigator based on CT per MLRC. Per MLRC, CR per CT=a complete radiologic response in lymph nodes &ELS with target nodes/nodal masses regressing to ≤1.5 cm in LDi &no ELS of disease; organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT=partial remission in lymph nodes & ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes &extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal, no new sites of lesions. Efficacy evaluable population=participants in dose expansion arms who received at least one dose of any component of the combination. As pre-specified in protocol, participants who received polatuzumab vedotin & venetoclax at RP2D in dose-escalation were also analysed in addition to expansion phase participants for efficacy analysis. Percentages have been rounded off to first decimal point.

End point type

Secondary

End point timeframe

Up to every 6 months until disease progression, the start of new anti-lymphoma treatment, or the end of the study, whichever occurs first (approximately 77 months)

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: It included participants in the dose expansion arms who received at least one dose of any component of the combination. As pre-specified in the protocol, participants who received polatuzumab vedotin and venetoclax at RP2D in dose-escalation phase were also analyzed in addition to expansion phase participants for efficacy analysis.

End point values	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	8	41	8	40
Units: percentage of participants
number (confidence interval 90%)	100.0 (68.77 to 100.00)	87.8 (76.05 to 95.07)	50.0 (19.29 to 80.71)	72.5 (58.61 to 83.75)

No statistical analyses for this end point

Secondary: Observed Serum Obinutuzumab Concentration

Top of page

End point title

Observed Serum Obinutuzumab Concentration ^[19]

End point description

1 cycle = 21 days. Pharmacokinetics (PK) evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Overall number analysed is the number of participants with data available for analysis. Number analysed is the number of participants with data available for analysis at the specified timepoint.Here, 9999= The data was not evaluable as the samples were below lower limit of quantification (BLLQ); 9999999= participants were not analysed for this PK endpoint at the given timepoint; 999999= Since only 1 participant was analysed, the geometric coefficient of variation was not evaluable.

End point type

Secondary

End point timeframe

Pre-dose & 0.5 hours post-dose on Day 1 Cycles 1, 2, 4, & 6; and pre-dose on Day 1 of Months 2, 8, 14, 20; study drug discontinuation, Day 120 &1 year post-last dose (up to approximately 40 months)

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: This endpoint is applicable only for FL arms.

End point values	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G
Number of subjects analysed	7	3	3	3	9	8	39
Units: micrograms per milliliter (µg/mL)
geometric mean (geometric coefficient of variation)
Cycle (C)1 Day (D)1: Pre-dose (n=6,3,3,3,9,8,29)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C1 D1 0.5 h: Post Dose (n=5,3,3,3,9,5,38)	310 ( 21.2 )	360 ( 18.8 )	169 ( 60.2 )	342 ( 11.0 )	262 ( 106.0 )	438 ( 17.8 )	261 ( 115.1 )
C2 D1: Pre-dose (n=7,3,3,3,8,8,39)	327 ( 46.7 )	498 ( 20.6 )	288 ( 43.2 )	395 ( 17.0 )	435 ( 25.4 )	497 ( 20.3 )	422 ( 29.0 )
C2 D1: 0.5 hours (h) Post Dose (n=7,3,3,3,8,8,39)	637 ( 32.0 )	822 ( 17.0 )	512 ( 56.1 )	685 ( 17.8 )	800 ( 19.1 )	975 ( 19.3 )	834 ( 30.3 )
C4 D1: Pre-dose (n=7,3,2,3,8,7,36)	284 ( 50.9 )	496 ( 25.3 )	376 ( 9.6 )	337 ( 12.0 )	422 ( 20.3 )	454 ( 37.2 )	397 ( 40.5 )
C4 D1: 0.5 h Post Dose (n=7,3,2,3,8,7,36)	534 ( 62.9 )	842 ( 25.1 )	709 ( 20.1 )	732 ( 13.4 )	819 ( 18.6 )	925 ( 26.9 )	770 ( 25.6 )
C6 D1: Pre-dose (n=7,3,2,3,8,7,36)	288 ( 62.9 )	582 ( 26.5 )	338 ( 4.0 )	335 ( 10.2 )	437 ( 24.5 )	420 ( 44.5 )	428 ( 51.9 )
C6 D1: 0.5 h Post Dose (n=6,3,2,3,8,7,36)	582 ( 26.8 )	887 ( 19.6 )	490 ( 65.2 )	659 ( 14.3 )	857 ( 21.2 )	841 ( 28.1 )	807 ( 27.0 )
Maintenance Month 2 (6,3,1,3,8,7,31)	117 ( 471.2 )	294 ( 53.3 )	205 ( 999999 )	192 ( 11.7 )	273 ( 63.4 )	327 ( 57.6 )	291 ( 60.8 )
Maintenance Month 8 (3,1,1,2,7,6,20)	148 ( 161.8 )	184 ( 999999 )	191 ( 999999 )	114 ( 30.0 )	170 ( 40.2 )	210 ( 27.0 )	168 ( 72.0 )
Maintenance Month 14 (n=2,2,1,1,4,2,14)	189 ( 112.9 )	226 ( 28.9 )	197 ( 999999 )	138 ( 999999 )	133 ( 23.5 )	190 ( 17.9 )	168 ( 41.3 )
Maintenance Month 20 (n=1,2,1,0,4,4,12)	242 ( 999999 )	218 ( 30.7 )	74.0 ( 999999 )	9999999 ( 9999999 )	156 ( 44.2 )	144 ( 26.9 )	180 ( 62.0 )
Study Drug Discon. Visit (n=2,2,2,3,2,4,16)	9.61 ( 438943.9 )	134 ( 1414.6 )	4.48 ( 2973890.2 )	66.6 ( 271.0 )	262 ( 11.9 )	212 ( 34.8 )	148 ( 110.1 )
Unscheduled Visit (n=3,0,0,0,1,1,6)	74.4 ( 28339.6 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	192 ( 999999 )	144 ( 999999 )	276 ( 124.8 )
Day 120 Post Last Dose (n=1,0,3,1,4,5,10)	39.9 ( 999999 )	9999999 ( 9999999 )	1.72 ( 1634893.3 )	0.660 ( 999999 )	41.2 ( 89.5 )	94.6 ( 85.6 )	44.1 ( 274.2 )
One Year Post Last Dose (n=4,0,2,1,3,1,6)	0.0410 ( 20351.2 )	9999999 ( 9999999 )	0.0585 ( 372.7 )	0.00680 ( 999999 )	0.244 ( 716.1 )	0.0820 ( 999999 )	4.89 ( 9002.8 )

No statistical analyses for this end point

Secondary: Observed Serum Rituximab Concentration

Top of page

End point title

Observed Serum Rituximab Concentration ^[20]

End point description

PK evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Overall number analysed is the number of participants with data available for analysis. Number analysed is the number of participants with data available for analysis at the specified timepoint.Here, 9999= The data was not evaluable as the samples were BLLQ; 999999= Since only 1 participant was analysed, the geometric coefficient of variation was not evaluable.

End point type

Secondary

End point timeframe

Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1 and 6; pre-dose on Day 1 of Cycles 2 and 4; (1 cycle = 21 days)

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: This endpoint is applicable only for DLBCL arms.

End point values	DLBCL: Dose Escalation: 1.8P+400V+375R	DLBCL Dose Escalation: 1.8P+600V+375R	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	2	6	6	39
Units: µg/mL
geometric mean (geometric coefficient of variation)
C1 D1: Pre-dose (n=2,2,1,9)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C1 D1: 05 hPost Dose (n=2,6,6,39)	199 ( 25.4 )	189 ( 6.8 )	255 ( 14.0 )	146 ( 159.3 )
C2 D1: Within 5 h Pre-dose (n=2,6,6,36)	49.3 ( 17.2 )	38.9 ( 61.7 )	71.0 ( 42.1 )	50.1 ( 30.5 )
C4 D1: Within 5 h Pre-dose (n=2,2,4,29)	88.9 ( 11.1 )	39.3 ( 71.0 )	126 ( 16.5 )	88.1 ( 43.4 )
C6 D1: Pre-dose (n=2,1,3,24)	120 ( 8.8 )	20.9 ( 999999 )	151 ( 32.4 )	117 ( 43.4 )
C6 D1: 0.5 h Post Dose (n=2,1,3,23)	303 ( 12.4 )	182 ( 999999 )	229 ( 36.9 )	308 ( 27.2 )

No statistical analyses for this end point

Secondary: Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin

Top of page

End point title

Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin

End point description

Total antibody is an analyte of polatuzumab vedotin. PK evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Overall number analysed is the number of participants with data available for analysis. Number analysed is the number of participants with data available for analysis at the specified timepoint. Here, 9999= The data was not evaluable as the samples were BLLQ; 99999= Geometric coefficient of variation was not evaluable as the samples were BLLQ; 999999= Since only 1 participant was analysed, the geometric coefficient of variation was not evaluable; 9999999= participants were not analysed for this PK endpoint at the given timepoint, 99999999=Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not calculated.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1, 2 and 4; study drug discontinuation visit; Day 120 and 1 year post-last dose (up to approximately 16 months) (1 cycle=21 days)

End point values	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL: Dose Escalation: 1.8P+400V+375R	DLBCL Dose Escalation: 1.8P+600V+375R	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	7	3	3	3	8	8	41	3	6	7	39
Units: µg/mL
geometric mean (geometric coefficient of variation)
C1 D1: Predose(n=7,3,3,3,8,7,41,2,6,7,39)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C2 D1: Predose(n=7,3,3,3,8,8,40,3,6,6,37)	0.798 ( 404.2 )	3.14 ( 29.4 )	0.677 ( 6220.9 )	2.03 ( 46.4 )	1.75 ( 63.2 )	4.22 ( 31.1 )	1.73 ( 265.3 )	3.34 ( 56.6 )	2.23 ( 83.5 )	3.41 ( 30.9 )	3.04 ( 70.8 )
C4 D1: Predose(n=7,3,2,3,8,7,36,3,2,4,30)	2.73 ( 76.1 )	6.12 ( 26.1 )	7.88 ( 9.5 )	5.40 ( 18.4 )	5.72 ( 33.5 )	8.19 ( 32.3 )	5.88 ( 63.7 )	6.84 ( 29.5 )	2.34 ( 82.1 )	8.22 ( 17.0 )	5.82 ( 45.7 )
Study Drug Discn.Visit(n=2,2,2,3,4,4,17,1,1,4,14)	0.0250 ( 99999 )	0.0250 ( 99999 )	0.0534 ( 99999 )	0.0250 ( 99999 )	0.0250 ( 99999 )	0.0900 ( 99999 )	0.110 ( 99999 )	2.43 ( 999999 )	4.71 ( 999999 )	1.38 ( 203.0 )	1.03 ( 471.1 )
Unscheduled Visit (n=0,0,0,0,0,0,5,0,0,0,0)	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	0.0571 ( 99999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )
Day 120 Post Last Dose (n=1,1,3,1,6,6,20,2,0,1,7)	0.0250 ( 999999 )	0.0250 ( 999999 )	0.0906 ( 99999 )	0.0250 ( 999999 )	0.0832 ( 99999 )	0.156 ( 99999 )	0.494 ( 468.8 )	0.385 ( 28.6 )	9999999 ( 9999999 )	0.759 ( 999999 )	1.37 ( 93.2 )
One Year Post Last Dose (n=4,0,2,1,3,1,11,1,1,0,3)	0.0250 ( 99999 )	9999999 ( 9999999 )	0.0250 ( 99999 )	0.0250 ( 999999 )	0.0250 ( 99999 )	0.0250 ( 999999 )	0.0294 ( 99999 )	0.0250 ( 999999 )	0.0250 ( 999999 )	9999999 ( 9999999 )	0.0457 ( 99999 )

No statistical analyses for this end point

Secondary: Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE)

Top of page

End point title

Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE)

End point description

acMMAE is an analyte of polatuzumab vedotin. PK evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Overall number analysed is the number of participants with data available for analysis. Number analysed is the number of participants with data available for analysis at the specified timepoint.Here, 9999= The data was not evaluable as the samples were below lower limit of quantification (BLLQ); 99999= Geometric coefficient of variation was not evaluable as the samples were BLLQ; 999999= Since only 1 participant was analysed, the geometric coefficient of variation was not evaluable;9999999= participants were not analysed for this PK endpoint at the given timepoint.

End point type

Secondary

End point timeframe

Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1, 2 and 4; post-dose on Days 8 and 15 of Cycle 1; predose on Day 1 of Cycle 6 (1 cycle=21 days)

End point values	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL: Dose Escalation: 1.8P+400V+375R	DLBCL Dose Escalation: 1.8P+600V+375R	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	7	3	3	3	9	8	40	3	6	8	39
Units: nanograms per milliliters (ng/mL)
geometric mean (geometric coefficient of variation)
C1 D1: Predose(n=7,3,3,3,9,8,40,3,6,8,39)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C1 D1: 0.5 h Post dose(n=6,3,3,3,9,8,39,3,6,8,38)	131 ( 19054.2 )	530 ( 22.2 )	451 ( 48.0 )	610 ( 3.4 )	645 ( 24.6 )	825 ( 20.8 )	613 ( 38.2 )	722 ( 25.3 )	628 ( 27.1 )	683 ( 22.2 )	481 ( 226.7 )
C1 D8: Dose (n=7,3,3,3,8,8,40,2,5,6,36)	19.1 ( 890.8 )	57.0 ( 19.3 )	9.87 ( 43972.4 )	49.3 ( 33.6 )	58.0 ( 39.7 )	88.9 ( 20.7 )	41.0 ( 192.1 )	45.6 ( 27.7 )	50.8 ( 42.6 )	77.0 ( 25.3 )	57.9 ( 42.2 )
C1 D15: Post Dose (n=7,3,3,3,8,8,39,3,6,6,37)	6.67 ( 421.2 )	22.9 ( 18.1 )	4.56 ( 5235.8 )	18.7 ( 24.2 )	17.7 ( 56.9 )	31.6 ( 15.3 )	14.4 ( 176.9 )	26.0 ( 69.8 )	19.8 ( 50.5 )	30.2 ( 21.5 )	22.3 ( 40.6 )
C2 D1: Predose (n=7,3,3,3,8,8,39,3,5,6,35)	3.69 ( 296.8 )	12.6 ( 36.9 )	3.25 ( 2446.9 )	9.34 ( 44.7 )	8.27 ( 62.6 )	16.7 ( 40.2 )	7.71 ( 209.4 )	14.9 ( 66.9 )	8.94 ( 100.6 )	14.8 ( 29.2 )	13.1 ( 45.3 )
C2 D1: 0.5 h Post Dose(n=7,3,3,3,8,8,39,3,6,6,37)	527 ( 27.3 )	594 ( 18.7 )	602 ( 36.8 )	555 ( 3.0 )	682 ( 24.0 )	844 ( 19.7 )	688 ( 20.7 )	749 ( 23.0 )	341 ( 353.1 )	748 ( 17.7 )	628 ( 27.6 )
C4 D1: Predose (n=7,3,2,3,8,7,37,3,2,4,30)	10.8 ( 69.4 )	18.8 ( 24.9 )	29.4 ( 10.1 )	19.7 ( 8.2 )	23.4 ( 35.0 )	27.5 ( 37.0 )	21.5 ( 53.3 )	24.8 ( 25.8 )	8.16 ( 245.5 )	30.1 ( 12.3 )	22.2 ( 49.8 )
C4 D1: 0.5 h Post Dose (n=7,3,2,3,8,6,37,3,2,4,29)	491 ( 28.1 )	587 ( 16.3 )	768 ( 29.5 )	620 ( 7.4 )	553 ( 90.9 )	474 ( 299.3 )	644 ( 66.8 )	968 ( 33.7 )	722 ( 1.8 )	775 ( 15.2 )	680 ( 25.9 )
C6 D1: Predose (n=7,3,2,3,8,7,33,2,1,3,24)	13.0 ( 58.5 )	4.62 ( 5273.1 )	23.5 ( 42.5 )	20.5 ( 3.7 )	28.6 ( 27.2 )	27.3 ( 35.9 )	25.2 ( 56.9 )	24.3 ( 24.4 )	3.73 ( 999999 )	31.5 ( 46.0 )	24.7 ( 54.4 )
Unscheduled Visit (n=2,0,0,0,0,0,2,0,0,0,0)	5.36 ( 99999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	11.3 ( 99999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )

No statistical analyses for this end point

Secondary: Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE

Top of page

End point title

Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE

End point description

MMAE is an analyte of polatuzumab vedotin. PK evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Overall number analysed is the number of participants with data available for analysis. Number analysed is the number of participants with data available for analysis at the specified timepoint.Here, 9999= The data was not evaluable as the samples were below lower limit of quantification (BLLQ); 99999= Geometric coefficient of variation was not evaluable as the samples were BLLQ; 999999= Since only 1 participant was analysed, the geometric coefficient of variation was not evaluable;9999999= participants were not analysed for this PK endpoint at the given timepoint. 99999999=Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not calculated.

End point type

Secondary

End point timeframe

Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1, 2 and 4; post-dose on Days 8 and 15 of Cycle 1; predose on Day 1 of Cycle 6 (1 cycle=21 days)

End point values	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL: Dose Escalation: 1.8P+400V+375R	DLBCL Dose Escalation: 1.8P+600V+375R	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	7	3	3	3	9	8	40	3	6	8	38
Units: ng/mL
geometric mean (geometric coefficient of variation)
C1 D1: Predose (n=7,3,3,3,9,8,39,3,6,8,38)	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )
C1 D1: 0.5 h Post Dose (n=6,3,3,3,9,8,40,3,6,8,38)	0.313 ( 725.2 )	0.236 ( 31.1 )	1.04 ( 575.7 )	0.417 ( 60.3 )	0.507 ( 112.0 )	9999 ( 9999 )	0.441 ( 208.3 )	0.249 ( 8.7 )	0.390 ( 89.0 )	0.262 ( 61.9 )	0.263 ( 90.8 )
C1 D8: Post Dose (n=7,3,3,3,8,8,40,3,5,6,36)	1.14 ( 34.8 )	57.5 ( 1.46 )	1.57 ( 63.6 )	1.06 ( 43.6 )	1.66 ( 69.9 )	0.323 ( 79.3 )	1.81 ( 65.3 )	2.34 ( 54.7 )	2.77 ( 63.1 )	2.51 ( 96.3 )	2.51 ( 65.1 )
C1 D15: Post Dose (n=7,3,3,3,8,8,39,3,6,6,37)	0.225 ( 87.4 )	0.310 ( 60.2 )	0.213 ( 174.3 )	0.341 ( 55.9 )	0.461 ( 76.6 )	2.26 ( 76.3 )	0.444 ( 99.8 )	0.675 ( 144.7 )	0.927 ( 89.8 )	0.778 ( 77.9 )	0.723 ( 63.3 )
C2 D1: Predose (n=7,3,3,3,8,8,39,3,6,6,37)	0.0575 ( 117.0 )	0.103 ( 47.1 )	0.0565 ( 132.5 )	0.0982 ( 75.3 )	0.0866 ( 141.8 )	0.688 ( 73.8 )	0.113 ( 136.1 )	0.221 ( 199.1 )	0.311 ( 76.4 )	0.266 ( 161.7 )	0.227 ( 66.1 )
C2 D1: 0.5 h Post Dose (n=7,3,3,3,8,8,39,3,6,6,37)	0.152 ( 46.2 )	0.184 ( 29.0 )	0.399 ( 104.7 )	0.175 ( 57.0 )	0.231 ( 76.5 )	0.150 ( 41.9 )	0.257 ( 63.8 )	0.343 ( 122.0 )	0.564 ( 76.4 )	0.407 ( 116.2 )	0.322 ( 55.9 )
C4 D1: Predose (n=7,3,2,3,8,8,36,3,2,4,30)	0.131 ( 58.2 )	0.106 ( 48.3 )	0.180 ( 62.4 )	0.172 ( 46.8 )	0.155 ( 46.5 )	0.263 ( 46.5 )	0.167 ( 81.0 )	0.238 ( 75.5 )	0.459 ( 103.4 )	0.295 ( 90.5 )	0.220 ( 72.7 )
C4 D1: 0.5h Post Dose (n=7,3,2,3,8,7,37,3,2,4,29)	0.235 ( 84.2 )	0.163 ( 50.6 )	0.255 ( 48.6 )	0.270 ( 31.6 )	0.209 ( 42.0 )	0.206 ( 36.2 )	0.260 ( 56.2 )	0.331 ( 77.4 )	0.565 ( 107.5 )	0.364 ( 65.6 )	0.311 ( 57.7 )
C6 D1: Predose (n=7,3,2,3,8,6,35,2,1,2,24	0.107 ( 73.4 )	0.120 ( 62.3 )	0.0715 ( 99999 )	0.239 ( 17.2 )	0.189 ( 37.2 )	0.289 ( 55.2 )	0.162 ( 94.9 )	0.197 ( 275.2 )	0.795 ( 999999 )	0.334 ( 62.1 )	0.211 ( 93.8 )
Unscheduled Visit (n=2,0,0,0,0,7,2,0,0,0,0)	0.0180 ( 99999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	0.196 ( 89.0 )	0.0852 ( 99999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )

No statistical analyses for this end point

Secondary: Observed Plasma Venetoclax Concentration

Top of page

End point title

Observed Plasma Venetoclax Concentration

End point description

1 cycle = 21 days. PK evaluable population included all participants who had at least one evaluable PK sample post dose for at least one analyte. Overall number analysed is the number of participants with data available for analysis. Number analysed is the number of participants with data available for analysis at the specified timepoint.Here, 9999= The data was not evaluable as the samples were below lower limit of quantification (BLLQ); 99999999= Values were LTR for 1 participant. Since data was evaluable only for 1 participant geometric co-efficient of variation was not calculated; 999999= Since only 1 participant was analysed, the geometric coefficient of variation was not evaluable; 9999999= participants were not analysed for this PK endpoint at the given timepoint.

End point type

Secondary

End point timeframe

Pre-dose and 4 hours post-dose on Day 1 Cycle 1, pre-dose & 2, 4, 6, & 8 hours post-dose on Day 1 Cycle 2, pre-dose & 4hours post-dose on Day 1 Cycle 4 & pre-dose on Day 1 Cycle 6; (1 cycle = 21 days)

End point values	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL: Dose Escalation: 1.8P+400V+375R	DLBCL Dose Escalation: 1.8P+600V+375R	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	7	3	3	3	9	8	41	3	6	7	40
Units: µg/mL
geometric mean (geometric coefficient of variation)
C1 D1: Predose(n=0,0,0,0,0,0,0,0,0,0,2)	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999 ( 9999 )
C1 D1: PostDose(n=6,3,3,3,9,8,41,3,6,7,40)	0.624 ( 94.6 )	0.247 ( 162.1 )	0.108 ( 53.3 )	0.244 ( 149.1 )	0.796 ( 86.5 )	0.811 ( 310.3 )	0.964 ( 69.2 )	0.503 ( 47.9 )	0.915 ( 47.4 )	1.21 ( 103.4 )	0.841 ( 94.8 )
C2 D1: Predose(n=7,3,3,3,8,8,39,3,6,6,35)	0.336 ( 99.3 )	0.347 ( 144.3 )	0.453 ( 71.9 )	0.943 ( 28.5 )	0.298 ( 2853.1 )	0.282 ( 498.3 )	0.555 ( 1134.4 )	0.529 ( 135.6 )	0.952 ( 139.7 )	0.852 ( 1812.3 )	0.329 ( 1047.7 )
C2 D1: 2 h PostDose(n=7,3,2,2,7,6,1,3,5,5,1)	0.532 ( 119.2 )	0.306 ( 107.3 )	0.351 ( 129.3 )	0.822 ( 54.8 )	0.769 ( 131.0 )	0.921 ( 74.0 )	2.69 ( 999999 )	0.632 ( 90.1 )	1.08 ( 82.0 )	1.01 ( 464.7 )	999999 ( 5.13 )
C2 D1: 4 h PostDose(n=7,3,3,3,8,7,39,3,6,6,39)	1.12 ( 102.2 )	0.572 ( 49.1 )	0.548 ( 51.0 )	1.31 ( 22.5 )	1.65 ( 69.4 )	2.04 ( 39.2 )	1.99 ( 59.0 )	0.830 ( 75.3 )	1.49 ( 43.1 )	2.03 ( 131.4 )	1.50 ( 74.5 )
C2 D1: 6 h PostDose(n=7,3,2,2,7,6,1,3,5,5,1)	1.38 ( 83.4 )	0.933 ( 72.1 )	1.21 ( 24.8 )	1.99 ( 5.7 )	2.15 ( 51.9 )	2.55 ( 28.0 )	4.82 ( 999999 )	0.870 ( 98.1 )	1.96 ( 57.5 )	2.74 ( 117.9 )	5.95 ( 999999 )
C2 D1: 8 h PostDose(n=7,3,2,2,6,5,1,3,4,4,1)	1.40 ( 74.9 )	0.803 ( 76.7 )	1.45 ( 32.3 )	2.24 ( 18.4 )	2.46 ( 59.8 )	2.53 ( 32.7 )	3.02 ( 999999 )	0.886 ( 87.6 )	1.88 ( 70.8 )	2.85 ( 94.7 )	6.66 ( 999999 )
C4 D1: Predose(n=7,3,2,3,8,7,36,3,2,4,30)	0.259 ( 157.2 )	0.0344 ( 15072.4 )	0.302 ( 1.2 )	1.12 ( 40.2 )	0.551 ( 98.4 )	0.304 ( 1059.7 )	0.561 ( 401.2 )	0.0581 ( 1105.7 )	0.933 ( 74.2 )	0.826 ( 311.3 )	0.337 ( 1043.6 )
C4 D1: PostDose(n=0,0,0,0,0,0,0,0,0,0,2)	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	9999999 ( 9999999 )	1.04 ( 8.4 )
C6 D1: Predose(n=7,3,2,3,8,7,34,2,1,3,24)	0.252 ( 95.0 )	0.277 ( 178.7 )	0.0177 ( 99999 )	1.24 ( 56.1 )	0.595 ( 95.4 )	0.0266 ( 26843.8 )	0.509 ( 496.6 )	0.175 ( 187.9 )	1.90 ( 999999 )	0.0772 ( 101668.3 )	0.365 ( 780.9 )

No statistical analyses for this end point

Secondary: Number of Participants with Human Anti-Human Antibodies (HAHAs) to Obinutuzumab

Top of page

End point title

Number of Participants with Human Anti-Human Antibodies (HAHAs) to Obinutuzumab ^[21]

End point description

The number of participants with positive results for HAHAs, also called anti-drug antibodies (ADAs) against obinutuzumab at baseline & at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during study period. Treatment-induced ADA = negative or missing baseline ADA result at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than baseline. The immunogenicity population included participants with at least one predose and one postdose HAHA or ATA sample. Overall number analysed=number of participants with data available for analysis. Number analysed=number of participants with data available for analysis at a specified timepoint.

End point type

Secondary

End point timeframe

Baseline up to approximately 2 years after last dose (up to approximately 52 months)

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 participants who received obinutuzumab were included

End point values	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G
Number of subjects analysed	7	3	3	3	9	8	39
Units: participants
Baseline prev. of ADAs (n=3,7,3,2,9,7,39)	0	0	0	0	0	0	0
Post baseline inc. of ADAs (n=3,7,3,3,8,8,39)	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin

Top of page

End point title

Number of Participants with Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin

End point description

The number of participants with positive results for ATAs, also called ADAs against polatuzumab vedotin at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Immunogenicity population included participants with at least one predose and one postdose ATA assessment, with participants grouped according to histology. Number analysed=number of participants with data available for analysis.

End point type

Secondary

End point timeframe

Baseline up to 1 year post last dose (up to approximately 16 months)

End point values	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G	DLBCL: Dose Escalation: 1.8P+400V+375R	DLBCL Dose Escalation: 1.8P+600V+375R	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R
Number of subjects analysed	7	3	3	3	9	8	41	3	6	8	40
Units: participants
Baseline ADAs (n=3,6,3,3,9,7,3,6,8,41,40)	1	0	0	0	0	0	0	0	0	0	0
Post baseline ADAs (n=3,7,3,3,9,8,3,6,7,41,39)	1	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From study start to 24 months after last dose of study drug (approximately 56 months); DLBCL cohorts: From study start to 3 months after last dose of study drug (approximately 21 months)

Adverse event reporting additional description

Safety-evaluable population included all participants who received at least one dose of any component of the combination.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

DLBCL: Dose Escalation: 1.8P+400V+375R

Reporting group description

Participants received venetoclax, 400 mg, orally, once daily (QD) on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with rituximab, 375 mg/m^2, IV infusion, on Day 1 of Cycles 1-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved complete response (CR) or partial response (PR) at end of induction (EOI) received consolidation treatment until disease progression or unacceptable toxicity for up to 8 months. During consolidation treatment participants received venetoclax, 400 mg, QD, for up to 8 months and rituximab, 375 mg/m^2 on Day 1 of every other month (1 month=28 days) starting from Month 2 up to 8 months.

Reporting group title

DLBCL Dose Escalation: 1.8P+600V+375R

Reporting group description

Reporting group title

DLBCL Dose Escalation: 1.8P+800V+375R

Reporting group description

Reporting group title

DLBCL Dose Expansion: 1.8P+800V+375R

Reporting group description

Reporting group title

FL Dose Escalation: 1.4P+400V+1000G

Reporting group description

Participants received venetoclax, 400 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.4 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 400 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months.

Reporting group title

FL Dose Escalation: 1.4P+200V+1000G

Reporting group description

Reporting group title

FL Dose Escalation: 1.8P+400V+1000G

Reporting group description

Reporting group title

FL Dose Escalation: 1.4P+600V+1000G

Reporting group description

Reporting group title

FL Dose Escalation: 1.8P+600V+1000G

Reporting group description

Participants received venetoclax, 600 mg, orally, QD on Days 1-21 of Cycles 1-6 (1 cycle=21 days) along with obinutuzumab, 1000 mg, IV infusion, on Days 1, 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2-6 and polatuzumab vedotin, 1.8 mg/kg, IV infusion, on Day 1 of Cycles 1-6 as induction treatment. Thereafter participants who achieved CR, PR, or SD at EOI received maintenance treatment until disease progression or unacceptable toxicity for up to 24 months. During maintenance treatment participants received venetoclax, 600 mg, QD, for up to 8 months and obinutuzumab, 1000 mg on Day 1 of every other month (1 month=28 days) starting from Month 2 for up to 24 months

Reporting group title

FL Dose Escalation: 1.8P+800V+1000G

Reporting group description

Reporting group title

FL: Dose Expansion: 1.8P+800V+1000G

Reporting group description

Serious adverse events	DLBCL: Dose Escalation: 1.8P+400V+375R	DLBCL Dose Escalation: 1.8P+600V+375R	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	4 / 6 (66.67%)	2 / 8 (25.00%)	12 / 40 (30.00%)	4 / 7 (57.14%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 9 (22.22%)	6 / 8 (75.00%)	14 / 41 (34.15%)
number of deaths (all causes)	0	4	6	26	3	1	0	0	1	1	8
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MYELODYSPLASTIC SYNDROME
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
DEEP VEIN THROMBOSIS
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOTENSION
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
ADVERSE DRUG REACTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
MUCOSAL INFLAMMATION
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PYREXIA
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
BRONCHIECTASIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DYSPNOEA
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPOXIA
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RESPIRATORY FAILURE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
CONFUSIONAL STATE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
DEVICE LEAKAGE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
FALL
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HIP FRACTURE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INFUSION RELATED REACTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ULNA FRACTURE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
CARDIAC FAILURE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
ATRIAL FIBRILLATION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CARDIAC FAILURE CONGESTIVE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CARDIOMYOPATHY
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CORONARY ARTERY DISEASE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
ENCEPHALOPATHY
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SYNCOPE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
FEBRILE NEUTROPENIA
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	3 / 41 (7.32%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	3 / 3	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NEUTROPENIA
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
THROMBOCYTOPENIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
RETINAL DETACHMENT
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RETINAL TEAR
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CONSTIPATION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
DIARRHOEA
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VOMITING
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SMALL INTESTINAL OBSTRUCTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NAUSEA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
LIVER INJURY
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
ACUTE KIDNEY INJURY
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
BRONCHITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CELLULITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 PNEUMONIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
COVID-19
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CLOSTRIDIUM DIFFICILE INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
CLOSTRIDIUM DIFFICILE COLITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMOCYSTIS JIROVECII PNEUMONIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
NEUTROPENIC SEPSIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
LOCALISED INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 8 (12.50%)	0 / 40 (0.00%)	2 / 7 (28.57%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	3 / 41 (7.32%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 8	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
PNEUMONIA VIRAL
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
URINARY TRACT INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
SINUSITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PSEUDOMONAS INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VASCULAR DEVICE INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
VIRAL UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
HYPOPHOSPHATAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
HYPERVOLAEMIA
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
TUMOUR LYSIS SYNDROME
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	DLBCL: Dose Escalation: 1.8P+400V+375R	DLBCL Dose Escalation: 1.8P+600V+375R	DLBCL Dose Escalation: 1.8P+800V+375R	DLBCL Dose Expansion: 1.8P+800V+375R	FL Dose Escalation: 1.4P+400V+1000G	FL Dose Escalation: 1.4P+200V+1000G	FL Dose Escalation: 1.8P+400V+1000G	FL Dose Escalation: 1.4P+600V+1000G	FL Dose Escalation: 1.8P+600V+1000G	FL Dose Escalation: 1.8P+800V+1000G	FL: Dose Expansion: 1.8P+800V+1000G
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	6 / 6 (100.00%)	7 / 8 (87.50%)	38 / 40 (95.00%)	7 / 7 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	9 / 9 (100.00%)	8 / 8 (100.00%)	41 / 41 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
OCULAR SURFACE SQUAMOUS NEOPLASIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
OCULAR MELANOMA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
SKIN CANCER
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0
SKIN PAPILLOMA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0
SQUAMOUS CELL CARCINOMA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	3 / 41 (7.32%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	9
TUMOUR HAEMORRHAGE
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Vascular disorders
HOT FLUSH
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	2 / 8 (25.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	2	2	0
FLUSHING
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	1
POOR VENOUS ACCESS
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
HYPOTENSION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	3 / 41 (7.32%)
occurrences all number	0	0	1	1	0	0	0	0	1	0	3
HYPERTENSION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	3 / 41 (7.32%)
occurrences all number	0	0	0	1	0	0	0	0	0	3	6
SUPERFICIAL VEIN THROMBOSIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1
Surgical and medical procedures
TOOTH EXTRACTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0
General disorders and administration site conditions
ADVERSE DRUG REACTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
ASTHENIA
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	2	0	0	2	0	1	0	0
CHEST DISCOMFORT
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	1	0
CHEST PAIN
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	2	1	0	0	0	0	0	0	0	1
INJECTION SITE BRUISING
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
FATIGUE
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	3 / 8 (37.50%)	10 / 40 (25.00%)	5 / 7 (71.43%)	2 / 3 (66.67%)	2 / 3 (66.67%)	1 / 3 (33.33%)	2 / 9 (22.22%)	3 / 8 (37.50%)	13 / 41 (31.71%)
occurrences all number	1	1	3	10	7	2	2	2	2	3	14
EARLY SATIETY
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	0
CHILLS
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 8 (0.00%)	3 / 40 (7.50%)	2 / 7 (28.57%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	3 / 41 (7.32%)
occurrences all number	1	1	0	3	3	1	1	0	0	0	6
INFLUENZA LIKE ILLNESS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	5 / 41 (12.20%)
occurrences all number	0	0	0	0	0	1	0	0	1	1	6
MUCOSAL INFLAMMATION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0
MALAISE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	1
INJECTION SITE EXTRAVASATION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
NON-CARDIAC CHEST PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
PAIN
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	4 / 41 (9.76%)
occurrences all number	0	2	0	0	0	0	0	0	1	1	4
OEDEMA PERIPHERAL
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	4 / 41 (9.76%)
occurrences all number	0	0	0	2	0	0	0	0	1	1	4
OEDEMA MUCOSAL
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
OEDEMA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0
PYREXIA
subjects affected / exposed	1 / 3 (33.33%)	2 / 6 (33.33%)	2 / 8 (25.00%)	6 / 40 (15.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	3 / 8 (37.50%)	5 / 41 (12.20%)
occurrences all number	1	3	2	7	1	0	0	0	2	7	5
Immune system disorders
SEASONAL ALLERGY
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
CYTOKINE RELEASE SYNDROME
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	0
DRUG HYPERSENSITIVITY
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
HYPOGAMMAGLOBULINAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	3 / 41 (7.32%)
occurrences all number	0	0	1	1	1	0	0	0	0	2	3
Reproductive system and breast disorders
ANISOMASTIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
PROSTATIC DISORDER
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
ENDOMETRIAL THICKENING
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
BREAST PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
BREAST CYST
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
DYSPHONIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	3	0	0	0	0	0	1
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
COUGH
subjects affected / exposed	2 / 3 (66.67%)	1 / 6 (16.67%)	0 / 8 (0.00%)	9 / 40 (22.50%)	3 / 7 (42.86%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	3 / 9 (33.33%)	4 / 8 (50.00%)	11 / 41 (26.83%)
occurrences all number	2	1	0	11	8	1	3	1	3	7	14
DRY THROAT
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
ATELECTASIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
HAEMOPTYSIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
EPISTAXIS
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	3
DYSPNOEA EXERTIONAL
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1
DYSPNOEA
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	4 / 40 (10.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	6 / 41 (14.63%)
occurrences all number	0	1	0	5	0	2	0	0	0	1	7
HICCUPS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0
NASAL CONGESTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	2 / 7 (28.57%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	3 / 41 (7.32%)
occurrences all number	0	0	0	0	2	0	0	0	2	0	5
LARYNGEAL INFLAMMATION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
HYPOXIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0
OROPHARYNGEAL PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	5 / 41 (12.20%)
occurrences all number	0	0	0	1	0	0	0	0	4	0	7
PRODUCTIVE COUGH
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	4 / 40 (10.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	3 / 41 (7.32%)
occurrences all number	0	1	0	5	1	0	0	0	1	2	4
PULMONARY CONGESTION
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
PULMONARY MASS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
UPPER RESPIRATORY TRACT INFLAMMATION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
THROAT IRRITATION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
RHINORRHOEA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	2	0	0	0	0	0	2	1
SINUS CONGESTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	2	1	1	1	0	1	0
SINUS PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
RHINITIS ALLERGIC
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1	1	0	0	0	0	1	2
WHEEZING
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0
UPPER-AIRWAY COUGH SYNDROME
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	2 / 7 (28.57%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	2
Psychiatric disorders
INSOMNIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	4 / 40 (10.00%)	2 / 7 (28.57%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	6 / 41 (14.63%)
occurrences all number	0	0	1	4	2	2	1	0	1	1	7
AGITATION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
HALLUCINATION
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	3	0	0	0	0	0	0	0
DEPRESSION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 8 (25.00%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	2	1	1	0	0	0	0	0	0
CONFUSIONAL STATE
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	3 / 40 (7.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	2	0	0	3	0	0	0	0	0	0	0
LIBIDO DECREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	2 / 7 (28.57%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 3 (66.67%)	1 / 9 (11.11%)	1 / 8 (12.50%)	4 / 41 (9.76%)
occurrences all number	0	1	0	0	2	2	0	2	1	1	9
AMYLASE INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 9 (0.00%)	1 / 8 (12.50%)	3 / 41 (7.32%)
occurrences all number	1	0	1	0	1	0	0	2	0	1	4
BILIRUBIN CONJUGATED INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0
BLOOD CREATININE INCREASED
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	2	1	0	0	0	0	0	0
BLOOD CALCIUM DECREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
BLOOD BILIRUBIN INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	2 / 41 (4.88%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	2
BLOOD ALKALINE PHOSPHATASE INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	0
BLOOD CALCIUM INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
BLOOD FIBRINOGEN DECREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
BLOOD GLUCOSE INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0
BLOOD IMMUNOGLOBULIN G DECREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
BLOOD LACTATE DEHYDROGENASE INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	1 / 8 (12.50%)	2 / 41 (4.88%)
occurrences all number	0	0	0	0	1	2	0	1	0	1	2
BLOOD PHOSPHORUS DECREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	3	0	0	0	0	0	1	2
BLOOD THYROID STIMULATING HORMONE INCREASED
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
EJECTION FRACTION DECREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
GAMMA-GLUTAMYLTRANSFERASE INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
INFLUENZA A VIRUS TEST POSITIVE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
PROTEIN TOTAL DECREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
OCCULT BLOOD POSITIVE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
WEIGHT DECREASED
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	2 / 8 (25.00%)	3 / 40 (7.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	7 / 41 (17.07%)
occurrences all number	0	2	2	3	1	0	0	0	0	1	7
URINARY CASTS PRESENT
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
RED BLOOD CELLS URINE POSITIVE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
PROTEIN URINE PRESENT
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	1
INTERNATIONAL NORMALISED RATIO INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
LIPASE INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
INCISIONAL HERNIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
FALL
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 8 (12.50%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	3 / 41 (7.32%)
occurrences all number	1	0	1	2	0	0	0	0	3	0	4
HAND FRACTURE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	1
HIP FRACTURE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
ARTHROPOD BITE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1
RIB FRACTURE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
PERIORBITAL HAEMATOMA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
LIGAMENT SPRAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
INFUSION RELATED REACTION
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	3 / 8 (37.50%)	2 / 40 (5.00%)	2 / 7 (28.57%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	4 / 9 (44.44%)	1 / 8 (12.50%)	13 / 41 (31.71%)
occurrences all number	2	0	4	2	2	0	3	0	4	1	14
SKIN LACERATION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
VASCULAR ACCESS SITE PAIN
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
TOOTH FRACTURE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	0	0	1	0	1	0	0	0	0	2
SUNBURN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
SKIN WOUND
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Cardiac disorders
CARDIAC FAILURE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
ATRIAL FIBRILLATION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0
TACHYCARDIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 8 (25.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	0	4	2	0	0	0	1	0	0	2
SINUS BRADYCARDIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	1
PALPITATIONS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	1
CORONARY ARTERY OCCLUSION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Nervous system disorders
HEADACHE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	3 / 40 (7.50%)	2 / 7 (28.57%)	1 / 3 (33.33%)	2 / 3 (66.67%)	1 / 3 (33.33%)	1 / 9 (11.11%)	2 / 8 (25.00%)	8 / 41 (19.51%)
occurrences all number	0	0	1	3	3	1	2	1	1	5	15
DISTURBANCE IN ATTENTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
DIZZINESS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	4 / 40 (10.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	3 / 41 (7.32%)
occurrences all number	0	0	1	5	0	0	1	0	0	3	4
DYSGEUSIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	3 / 41 (7.32%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	3
APHASIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
MIGRAINE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
LOSS OF CONSCIOUSNESS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
LETHARGY
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1	0	0	0	0	0	1	1
HYPOAESTHESIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	2	1	0	0	0	0	0	0	0
NEURALGIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
PERIPHERAL SENSORY NEUROPATHY
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	6 / 41 (14.63%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	6
PARAESTHESIA
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	3 / 40 (7.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	5 / 41 (12.20%)
occurrences all number	0	2	0	4	2	0	0	0	1	0	5
NEUROPATHY PERIPHERAL
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 8 (12.50%)	5 / 40 (12.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)	2 / 9 (22.22%)	3 / 8 (37.50%)	11 / 41 (26.83%)
occurrences all number	1	0	1	5	1	0	2	2	2	3	11
RESTING TREMOR
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
SCIATICA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	1
SOMNOLENCE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	3 / 40 (7.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	3	0	0	0	0	0	0	0
TASTE DISORDER
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
TREMOR
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	4
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	1 / 3 (33.33%)	2 / 6 (33.33%)	3 / 8 (37.50%)	5 / 40 (12.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	7 / 41 (17.07%)
occurrences all number	1	3	4	9	1	0	1	0	0	6	13
PANCYTOPENIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
NEUTROPENIA
subjects affected / exposed	2 / 3 (66.67%)	2 / 6 (33.33%)	5 / 8 (62.50%)	20 / 40 (50.00%)	2 / 7 (28.57%)	1 / 3 (33.33%)	2 / 3 (66.67%)	1 / 3 (33.33%)	4 / 9 (44.44%)	5 / 8 (62.50%)	17 / 41 (41.46%)
occurrences all number	5	7	7	64	3	3	2	5	17	23	46
LYMPHADENOPATHY
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
HYPERGAMMAGLOBULINAEMIA
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
FEBRILE NEUTROPENIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
THROMBOCYTOPENIA
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 8 (12.50%)	6 / 40 (15.00%)	3 / 7 (42.86%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 9 (22.22%)	4 / 8 (50.00%)	12 / 41 (29.27%)
occurrences all number	1	0	1	8	4	0	1	0	2	8	37
LEUKOPENIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	3 / 40 (7.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	1	9	1	0	0	0	1	2	4
Ear and labyrinth disorders
VERTIGO
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	1	0	0	1	0	0	0	0	1	1
OTORRHOEA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
EAR PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	1
DEAFNESS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1
Eye disorders
CATARACT
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0
DIPLOPIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
VISUAL IMPAIRMENT
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
VISUAL ACUITY REDUCED
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
VISION BLURRED
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
SCLERAL HYPERAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
PHOTOPHOBIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
LACRIMATION INCREASED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
EYE PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	1	0
Gastrointestinal disorders
DRY MOUTH
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	3 / 8 (37.50%)	3 / 41 (7.32%)
occurrences all number	0	0	1	0	0	0	0	0	1	4	3
DIARRHOEA
subjects affected / exposed	3 / 3 (100.00%)	1 / 6 (16.67%)	5 / 8 (62.50%)	16 / 40 (40.00%)	3 / 7 (42.86%)	2 / 3 (66.67%)	3 / 3 (100.00%)	2 / 3 (66.67%)	5 / 9 (55.56%)	6 / 8 (75.00%)	20 / 41 (48.78%)
occurrences all number	4	1	8	20	6	2	7	2	8	14	42
DENTAL CARIES
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1
CONSTIPATION
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 8 (12.50%)	6 / 40 (15.00%)	2 / 7 (28.57%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	4 / 8 (50.00%)	10 / 41 (24.39%)
occurrences all number	0	2	2	6	3	0	0	0	1	6	14
ABDOMINAL PAIN UPPER
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 9 (22.22%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	2	1	0
ABDOMINAL PAIN LOWER
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0	0	0
ABDOMINAL PAIN
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	3 / 8 (37.50%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	5 / 41 (12.20%)
occurrences all number	0	2	3	1	1	0	1	0	0	2	6
ABDOMINAL DISTENSION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	2 / 40 (5.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	0	1	2	0	1	1	0	0	0	7
DYSPEPSIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 9 (11.11%)	0 / 8 (0.00%)	6 / 41 (14.63%)
occurrences all number	0	0	1	1	0	0	1	1	1	0	8
ABDOMINAL DISCOMFORT
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	2	1	0	0	0	0	0	2	0
GASTROINTESTINAL DISORDER
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
FLATULENCE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 8 (25.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	0	2	2	0	0	0	0	0	0	2
DYSPHAGIA
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	1	0	0	1	1	0	0	0	0	0	1
FAECES DISCOLOURED
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0
FAECES SOFT
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
GASTROINTESTINAL PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
GASTROOESOPHAGEAL REFLUX DISEASE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 9 (11.11%)	2 / 8 (25.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	2	0	0	1	1	1	2	1
HAEMORRHOIDS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	2
ORAL DISCHARGE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
ODYNOPHAGIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
NAUSEA
subjects affected / exposed	3 / 3 (100.00%)	3 / 6 (50.00%)	1 / 8 (12.50%)	14 / 40 (35.00%)	2 / 7 (28.57%)	1 / 3 (33.33%)	2 / 3 (66.67%)	1 / 3 (33.33%)	2 / 9 (22.22%)	4 / 8 (50.00%)	23 / 41 (56.10%)
occurrences all number	4	4	1	15	3	1	2	1	2	6	35
MUCOUS STOOLS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
MOUTH ULCERATION
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	1	0	0	1	0	0	0	0	0
ORAL PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
VOMITING
subjects affected / exposed	2 / 3 (66.67%)	3 / 6 (50.00%)	4 / 8 (50.00%)	8 / 40 (20.00%)	2 / 7 (28.57%)	0 / 3 (0.00%)	2 / 3 (66.67%)	2 / 3 (66.67%)	1 / 9 (11.11%)	3 / 8 (37.50%)	11 / 41 (26.83%)
occurrences all number	3	3	11	8	3	0	2	3	2	4	17
TOOTHACHE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	3	0
STOMATITIS
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	1 / 41 (2.44%)
occurrences all number	0	1	0	0	0	0	0	0	0	2	1
RECTAL HAEMORRHAGE
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Hepatobiliary disorders
HYPERBILIRUBINAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
HEPATIC STEATOSIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1
CHOLELITHIASIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
HYPERTRANSAMINASAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Skin and subcutaneous tissue disorders
ACTINIC KERATOSIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
ALOPECIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	1 / 7 (14.29%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	3 / 41 (7.32%)
occurrences all number	0	0	0	1	1	1	0	0	1	1	3
COLD SWEAT
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
DERMATITIS ALLERGIC
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
DRY SKIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	3 / 40 (7.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	3	0	0	0	0	0	0	0
ECCHYMOSIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0
ECZEMA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0
HYPERHIDROSIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1	0	0	0	0	0	1	1
ERYTHEMA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	1
HYPERKERATOSIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	1
INGROWING NAIL
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
MILIARIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
NIGHT SWEATS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1	0	0	0	0	1	2	1
ONYCHOMADESIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
PRURITUS
subjects affected / exposed	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 8 (12.50%)	3 / 40 (7.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	2 / 41 (4.88%)
occurrences all number	1	1	1	3	0	0	0	0	0	1	2
RASH ERYTHEMATOUS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
RASH
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	2 / 40 (5.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	1 / 8 (12.50%)	4 / 41 (9.76%)
occurrences all number	0	0	1	2	0	1	0	0	3	1	7
SKIN HYPERTROPHY
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
SKIN LESION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
SKIN ULCER
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
SOLAR LENTIGO
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	5	0	0	0	0
Renal and urinary disorders
POLLAKIURIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1
HAEMATURIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
DYSURIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1	1	0	0	0	1	1	1
RENAL IMPAIRMENT
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
URINE ABNORMALITY
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
URINARY TRACT PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
URINARY INCONTINENCE
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	3 / 40 (7.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
BACK PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 8 (25.00%)	3 / 40 (7.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	8 / 41 (19.51%)
occurrences all number	0	0	2	3	1	0	0	0	0	1	8
ARTHRITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	1
ARTHRALGIA
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 8 (12.50%)	4 / 40 (10.00%)	2 / 7 (28.57%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 9 (11.11%)	3 / 8 (37.50%)	7 / 41 (17.07%)
occurrences all number	0	1	1	5	3	0	2	0	1	8	8
BONE PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	2 / 8 (25.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	2	0
FLANK PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1
MUSCULOSKELETAL PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	1 / 7 (14.29%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	1	1	1	0	0	0	1	0
MUSCULOSKELETAL DISCOMFORT
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0
MUSCULOSKELETAL CHEST PAIN
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
MUSCLE TIGHTNESS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
MUSCLE SPASMS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1	0	0	0	0	0	1	1
JOINT STIFFNESS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	0
GROIN PAIN
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 8 (25.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	2	1	0	0	1	0	0	0	2
MYALGIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0
PAIN IN JAW
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0
PLANTAR FASCIITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
PAIN IN EXTREMITY
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	4 / 41 (9.76%)
occurrences all number	0	0	1	1	1	0	1	0	0	5	8
OSTEOPENIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0
OSTEOARTHRITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Infections and infestations
CANDIDA INFECTION
subjects affected / exposed	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	2	1	0	0	0	1	0	0	0	0
CAMPYLOBACTER INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
BRONCHITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1	12	0	0	0	0	1	2
BACTERIAL DISEASE CARRIER
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
CHRONIC SINUSITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
COVID-19
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	2
CONJUNCTIVITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1
CLOSTRIDIUM DIFFICILE INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
CLOSTRIDIUM DIFFICILE COLITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
EAR INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	2
FUNGAL SKIN INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
GASTROENTERITIS
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
GASTROINTESTINAL VIRAL INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
OTITIS MEDIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	3 / 41 (7.32%)
occurrences all number	0	1	0	1	0	0	1	0	1	4	5
NASOPHARYNGITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	3 / 41 (7.32%)
occurrences all number	0	0	0	2	0	0	0	0	2	1	4
ORAL CANDIDIASIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
HERPES ZOSTER
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	2 / 7 (28.57%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1	2	0	0	0	0	1	1
RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	2
RHINITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
RHINOVIRUS INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	3 / 41 (7.32%)
occurrences all number	0	0	0	0	2	1	0	0	0	0	3
SINUSITIS
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 9 (11.11%)	4 / 8 (50.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	0	0	0	3	1	1	6	3
SKIN INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0
TOOTH INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
PHARYNGITIS STREPTOCOCCAL
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
PNEUMONIA
subjects affected / exposed	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	1	0	0	1	0	0	0	1	0	0	1
VULVOVAGINAL MYCOTIC INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
URINARY TRACT INFECTION ENTEROCOCCAL
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
URINARY TRACT INFECTION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	1 / 7 (14.29%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 9 (22.22%)	1 / 8 (12.50%)	3 / 41 (7.32%)
occurrences all number	0	0	1	2	1	0	2	0	4	1	4
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	3 / 8 (37.50%)	3 / 40 (7.50%)	4 / 7 (57.14%)	0 / 3 (0.00%)	2 / 3 (66.67%)	2 / 3 (66.67%)	2 / 9 (22.22%)	2 / 8 (25.00%)	11 / 41 (26.83%)
occurrences all number	0	1	4	3	4	0	2	2	2	3	18
Metabolism and nutrition disorders
DECREASED APPETITE
subjects affected / exposed	1 / 3 (33.33%)	3 / 6 (50.00%)	4 / 8 (50.00%)	6 / 40 (15.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	2 / 8 (25.00%)	5 / 41 (12.20%)
occurrences all number	1	3	5	7	0	0	0	0	1	2	6
DEHYDRATION
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	3 / 40 (7.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	0
HYPOALBUMINAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	1
HYPERURICAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	3 / 40 (7.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	3 / 41 (7.32%)
occurrences all number	0	0	0	3	0	0	1	0	0	0	3
HYPERPHOSPHATAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0
HYPOCALCAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	3
HYPERGLYCAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	1 / 8 (12.50%)	4 / 41 (9.76%)
occurrences all number	0	0	0	2	0	1	0	1	0	2	4
HYPERCALCAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	2 / 40 (5.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	0
GOUT
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
HYPERKALAEMIA
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0	0	0	0
HYPOPHOSPHATAEMIA
subjects affected / exposed	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	1 / 40 (2.50%)	0 / 7 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	4 / 41 (9.76%)
occurrences all number	0	1	0	1	0	0	1	0	2	2	8
HYPONATRAEMIA
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 40 (0.00%)	0 / 7 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	2 / 41 (4.88%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	2
HYPOMAGNESAEMIA
subjects affected / exposed	0 / 3 (0.00%)	3 / 6 (50.00%)	1 / 8 (12.50%)	1 / 40 (2.50%)	1 / 7 (14.29%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	4	1	1	1	1	0	0	0	0	2
HYPOKALAEMIA
subjects affected / exposed	0 / 3 (0.00%)	4 / 6 (66.67%)	3 / 8 (37.50%)	4 / 40 (10.00%)	2 / 7 (28.57%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	3 / 8 (37.50%)	4 / 41 (9.76%)
occurrences all number	0	4	3	5	2	0	1	0	0	6	5
TUMOUR LYSIS SYNDROME
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
VITAMIN D DEFICIENCY
subjects affected / exposed	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 40 (0.00%)	1 / 7 (14.29%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 41 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

26 Aug 2015

1. Inadvertent wording corrected regarding drug name: lenalidomide replaced with venetoclax. 2. Corrected schedule of imaging assessments for both relapsed/refractory FL and DLBCL patients so that the interim imaging scan should occur 7 days prior to C3D1.

01 Aug 2016

1. The amendment revised the DLT criteria, to include an additional cohort with a lower starting dose of venetoclax, and restart enrollment based on modified risk categorization for tumor lysis syndrome (TLS). 2. Added Cohort 1a with starting doses of 200 mg venetoclax and 1.4 mg/kg polatuzumab vedotin to collect safety data for this combination with obinutuzumab in response to observed adverse events. Cohort 1 will be repeated with the dose levels of 400 mg venetoclax and 1.4 mg/kg polatuzumab vedotin. 3. Enrollment rules into the dose escalation phase have been updated for participants’ safety considerations. A sequential enrollment instead of a parallel enrolment will be used for each of the two dosing groups. 4. Added exclusion of participants with Grade 3b FL and a history of transformation of indolent disease to DLBCL in order to focus on a more homogenous patient population. 5. Clarified that CR at EOI on the basis of CT alone is to be determined by the IRC in addition to the investigator 6. Clarified the Modified Lugano Criteria for designation of PET-CT on the basis of PR to also include requirement of a CR or PR on CT-based response criteria. 7. Clarified pharmacokinetic and immunogenicity sampling schedule time windows.

17 Jan 2017

1. Protocol was updated to clarify that participants with R/R DLBCL were to receive polatuzumab vedotin and venetoclax in 2. The study design was updated to include a dose-escalation phase in R/R DLBCL participants to assess the maximum tolerated dose of venetoclax when combined with rituximab and polatuzumab at the 1.8 mg/kg dose level. Only venetoclax dosing will be escalated. combination with rituximab instead of obinutuzumab. 3. The defined primary populations to be analyzed was changed to include participants who received at least one dose of any component of the combination. 4. The immunogenicity analysis was updated to clarify that human anti-human antibodies will be collected for patients receiving obinutuzumab. 5. The interim analysis was clarified to state that enrollment would not be stopped in the case of higher than expected efficacy.

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

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

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

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with CR at EOI Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans

Primary: Percentage of Participants with CR at EOI Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans

Primary: FL Cohorts: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Primary: FL Cohorts: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Primary: DLBCL Cohorts: Percentage of Participants with AEs and SAEs

Primary: DLBCL Cohorts: Percentage of Participants with AEs and SAEs

Primary: RP2D of Polatuzumab Vedotin

Primary: RP2D of Polatuzumab Vedotin

Primary: Number of Participants with Dose-Limiting Toxicities (DLTs )

Primary: Number of Participants with Dose-Limiting Toxicities (DLTs )

Primary: RP2D of Venetoclax

Primary: RP2D of Venetoclax

Secondary: Percentage of Participants with CR at EOI, Determined by the Investigator on the Basis of PET-CT scans

Secondary: Percentage of Participants with CR at EOI, Determined by the Investigator on the Basis of PET-CT scans

Secondary: Percentage of Participants with CR at EOI, Determined by the IRC on the Basis of CT Scans Alone

Secondary: Percentage of Participants with CR at EOI, Determined by the IRC on the Basis of CT Scans Alone

Secondary: Percentage of Participants with CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone

Secondary: Percentage of Participants with CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone

Secondary: Percentage of Participants with Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans

Secondary: Percentage of Participants with Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans

Secondary: Percentage of Participants with OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans

Secondary: Percentage of Participants with OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans

Secondary: Percentage of Participants with OR at EOI, Determined by an IRC on the Basis of CT Scans Alone

Secondary: Percentage of Participants with OR at EOI, Determined by an IRC on the Basis of CT Scans Alone

Secondary: Percentage of Participants with OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone

Secondary: Percentage of Participants with OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone

Secondary: Percentage of Participants with Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone

Secondary: Percentage of Participants with Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone

Secondary: Observed Serum Obinutuzumab Concentration

Secondary: Observed Serum Obinutuzumab Concentration

Secondary: Observed Serum Rituximab Concentration

Secondary: Observed Serum Rituximab Concentration

Secondary: Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin

Secondary: Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin

Secondary: Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE)

Secondary: Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE)

Secondary: Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE

Secondary: Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE

Secondary: Observed Plasma Venetoclax Concentration

Secondary: Observed Plasma Venetoclax Concentration

Secondary: Number of Participants with Human Anti-Human Antibodies (HAHAs) to Obinutuzumab

Secondary: Number of Participants with Human Anti-Human Antibodies (HAHAs) to Obinutuzumab

Secondary: Number of Participants with Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin

Secondary: Number of Participants with Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information